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Lipid Mediators in Cardiovascular Physiology and Disease

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Cardiovascular Signaling in Health and Disease

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Abstract

Bioactive lipids have taken the center stage in the last decade as dynamic mediators of cellular signaling and regulation. Lipids can directly and indirectly modify cellular processes that are independent from their utilization as fuel or structural properties. Among those processes, bioactive lipids are strong mediators of both cardiac and vascular function through diverse mechanisms. One family of lipids includes oxylipins, lipids derived from 𝜔-3 and 𝜔-6 fatty acids such as arachidonic and linoleic acids. Oxylipins play an essential role in whole-body physiology and function including maintenance of cardiac health and vascular homeostasis through direct and indirect mechanisms such as oxylipin receptors or regulation of inflammation. Overactivation or chronic stimulation of oxylipin synthesis has been linked to atherosclerosis, endothelial dysfunction, fibroblast overactivation, myocardial dysfunction, and immune cell activation. Thus, oxylipins are important lipid mediators of cardiovascular physiology and disease.

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Abbreviations

11,12-EET:

11,12-Epoxyeicosatrienoic acid

12,13-diHOME:

(9Z,12S,13S)-12,13-Dihydroxy-9-octadecenoic acid

13-HODE:

13-Hydroxyoctadecadienoic acid

14,15-EET:

14,15-Epoxyeicosatrienoic acid

16 (R)-HETE:

16(R)-Hydroxyeicosatetraenoic acid

16 (S)-HETE:

16(S)-Hydroxyeicosatetraenoic acid

16-HETE:

16-Hydroxyeicosatetraenoic acid

17 (R)-HETE:

17(R)-Hydroxyeicosatetraenoic acid

17 (S)-HETE:

17(S)-Hydroxyeicosatetraenoic acid

17-HETE:

17-Hydroxyeicosatetraenoic acid

18 (R)-HETE:

18(R)-Hydroxyeicosatetraenoic acid

18-HETE:

18-Hydroxyeicosatetraenoic acid

19-HETE:

19-Hydroxyeicosatetraenoic acid

20-HETE:

19-Hydroxyeicosatetraenoic acid

5,6-EET:

5,6-Epoxyeicosatrienoic acid

8,9-EET:

8,9-Epoxyeicosatrienoic acid

9-HODE:

9-Hydroxyoctadecadienoic acid

9,10-diHOME:

(9R,10R,12Z)-9,10-Dihydroxyoctadec-12-enoic acid

AA:

Arachidonic acid (20:4)

ACS:

Acyl-CoA synthase

ALOX12:

Arachidonate 12-lipoxygenase, 12S Type

ALOX12B:

Arachidonate 12-lipoxygenase, 12R Type

ALOX15/LOX-1:

Arachidonate 15-lipoxygenase

ALOX15B:

Arachidonate 15-Lipoxygenase Type B

ALOX5:

Arachidonate 5-lipoxygenase

ALOXE3:

Arachidonate lipoxygenase 3

ATGL:

Adipose tissue triglyceride lipase

BAT:

Brown adipose tissue

BKCa:

Large-conductance voltage- and Ca2+-activated K+ channel

BW755c:

Dual lipoxygenase/cyclooxygenase inhibitor

CE:

Cholesteryl esters

CEH:

Cholesteryl-ester hydrolase

CES1:

Carboxylesterase

CHD:

Coronary heart disease

COX1:

Cyclooxygenase 1

COX2:

Cyclooxygenase 2

cPLA2𝛼:

Calcium-activated cPLA2

CVD:

Cardiovascular disease

CYP:

Cytochrome P450

CYP1A:

Cytochrome P450 Family 1 Subfamily A

CYP1B1:

Cytochrome P450 Family 1 Subfamily B Member 1

CYP2C:

Cytochrome P450 Family 2 Subfamily C

CYP2C8:

Cytochrome P450 Family 2 Subfamily C Member 8

CYP2C9:

Cytochrome P450 Family 2 Subfamily C Member 9

CYP2E:

Cytochrome P450 Family 2 Subfamily E

CYP2J:

Cytochrome P450 Family 2 Subfamily J

CYP2J2:

Cytochrome P450 Family 2 Subfamily J Member 2

CYP4A:

Cytochrome P450 Family 4 Subfamily A

CYP4F:

Cytochrome P450 Family 4 Subfamily F

CytC:

Cytochrome C

DAG:

Diacylglycerol

DGLA:

Dihomo-γ-linolenic acid

DHA:

Docosahexaenoic acid (22:6)

DHETs:

Dihydroxyeicosatrienoic acids

diHOME:

Dihydroxyoctadecenoic acid

dihomo-PGE2:

Dihomo-prostaglandin E2

DP1:

Prostanoid receptor D

EDHF:

Endothelium-derived hyperpolarizing factors

EET:

Epoxyeicosatrienoic acid

EP3:

Prostanoid receptor E3

EP4:

Prostanoid receptor E4

EPA:

Eicosapentaenoic acid (20:5)

EpOME:

Epoxyoctadecaenoic acid

ER:

Endoplasmic reticulum

ERK:

Extracellular-regulated kinases

FA:

Fatty acid

FAsn-1-lysoPL:

sn-1 Fatty acid lysophospholipid

FOXO:

Forkhead box O

FP:

Prostanoid receptor F

GPCRs:

G-protein-coupled receptors

GLA:

γ-Linolenic acid

HETE:

Hydroxyeicosatetraenoic acid

HODE:

Hydroxyoctadecadienoic acid

HSL:

Hormone-sensitive lipase

IL-13:

Interleukin-13

IL-1β:

Interleukin-1beta

IL-4:

Interleukin-4

IP:

Prostanoid receptor I

JNK:

c-Jun NH2-terminal kinases

LA:

Linoleic acid (18:2)

LDAH:

Lipid droplet–associated hydrolase

LOX:

Lipoxygenase

LTA4:

Leukotriene A4

LTB4:

Leukotriene B4

LTC4:

Leukotriene C4

lysoPL:

Lysophospholipids

MAPK:

Mitogen-activated protein kinase

MGL:

Monoacylglycerol lipase

Na+/K+-ATPase:

Sodium/potassium-transporting ATPase

NAFLD:

Non-alcoholic fatty liver disease

NCEH1:

Neutral cholesterol ester hydrolase 1

NO:

Nitric oxide

NOS1:

Nitric oxide synthase 1

NSAID:

Non-steroidal anti-inflammatory drug

p38:

P38 MAP Kinase

PG:

Prostaglandins

PGD2:

Prostaglandin D2

PGE1:

Prostaglandin E1

PGE2:

Prostaglandin E2

PGE3:

Prostaglandin E3

PGF2a:

Prostaglandin F2a

PGG2/PGH2:

Prostaglandin G2/H2

PGI2:

Prostacyclin

PKC:

Protein kinase C

PL:

Phospholipids

PLA1:

Phospholipase A1

PLA2:

Phospholipase A2

PLIN1:

Perilipin 1

PMN:

Polymorphonuclear cells

PUFAs:

Polyunsaturated fatty acids

PUFAsn-2-lysoPL:

sn-2 PUFA-lysophospholipid

R- :

Rectus

RyR:

Ryanodine receptor

S- :

Sinister

sEH/EPHX:

Soluble epoxide hydrolases/epoxide hydrolase

SERCA2a:

Sarcoplasmic reticulum calcium ATPase

sn-1/2 :

Nucleophilic substitution-1/2

SPMs:

Specialized pro-resolvin mediators

TAG:

Triacylglycerols

TP:

Thromboxane receptor

TXA2:

Thromboxane A2

TXB2:

Thromboxane B2

𝜔-3:

Omega-3 fatty acid

𝜔-6:

Omega-6 fatty acid

References

  1. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation. 2019;139(10):e56–e528.

    Article  PubMed  Google Scholar 

  2. Group WCRCW. World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions. Lancet Glob Health. 2019;7(10):e1332–e45.

    Article  Google Scholar 

  3. Said MA, van de Vegte YJ, Zafar MM, van der Ende MY, Raja GK, Verweij N, et al. Contributions of interactions between lifestyle and genetics on coronary artery disease risk. Curr Cardiol Rep. 2019;21(9):89.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Zhu L, Zhang Y, Guo Z, Wang M. Cardiovascular biology of prostanoids and drug discovery. Arterioscler Thromb Vasc Biol. 2020;40(6):1454–63.

    Article  CAS  PubMed  Google Scholar 

  5. Hildreth K, Kodani SD, Hammock BD, Zhao L. Cytochrome P450-derived linoleic acid metabolites EpOMEs and DiHOMEs: a review of recent studies. J Nutr Biochem. 2020;86:108484.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gabbs M, Leng S, Devassy JG, Monirujjaman M, Aukema HM. Advances in our understanding of oxylipins derived from dietary PUFAs. Adv Nutr. 2015;6(5):513–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Tacconelli S, Patrignani P. Inside epoxyeicosatrienoic acids and cardiovascular disease. Front Pharmacol. 2014;5:239.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Yuhki K, Kojima F, Kashiwagi H, Kawabe J, Fujino T, Narumiya S, et al. Roles of prostanoids in the pathogenesis of cardiovascular diseases: novel insights from knockout mouse studies. Pharmacol Ther. 2011;129(2):195–205.

    Article  CAS  PubMed  Google Scholar 

  9. Caligiuri SPB, Parikh M, Stamenkovic A, Pierce GN, Aukema HM. Dietary modulation of oxylipins in cardiovascular disease and aging. Am J Physiol Heart Circ Physiol. 2017;313(5):H903–H18.

    Article  PubMed  CAS  Google Scholar 

  10. Nayeem MA. Role of oxylipins in cardiovascular diseases. Acta Pharmacol Sin. 2018;39(7):1142–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hajeyah AA, Griffiths WJ, Wang Y, Finch AJ, O’Donnell VB. The biosynthesis of enzymatically oxidized lipids. Front Endocrinol (Lausanne). 2020;11:591819.

    Article  Google Scholar 

  12. Tourdot BE, Ahmed I, Holinstat M. The emerging role of oxylipins in thrombosis and diabetes. Front Pharmacol. 2014;4:176.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Liu X, Sims HF, Jenkins CM, Guan S, Dilthey BG, Gross RW. 12-LOX catalyzes the oxidation of 2-arachidonoyl-lysolipids in platelets generating eicosanoid-lysolipids that are attenuated by iPLA2gamma knockout. J Biol Chem. 2020;295(16):5307–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Liu X, Moon SH, Jenkins CM, Sims HF, Gross RW. Cyclooxygenase-2 mediated oxidation of 2-arachidonoyl-lysophospholipids identifies unknown lipid signaling pathways. Cell Chem Biol. 2016;23(10):1217–27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Liu GY, Moon SH, Jenkins CM, Sims HF, Guan S, Gross RW. Synthesis of oxidized phospholipids by sn-1 acyltransferase using 2-15-HETE lysophospholipids. J Biol Chem. 2019;294(26):10146–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jenkins CM, Yang K, Liu G, Moon SH, Dilthey BG, Gross RW. Cytochrome c is an oxidative stress-activated plasmalogenase that cleaves plasmenylcholine and plasmenylethanolamine at the sn-1 vinyl ether linkage. J Biol Chem. 2018;293(22):8693–709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Xu S, Zhang X, Liu P. Lipid droplet proteins and metabolic diseases. Biochim Biophys Acta Mol Basis Dis. 2018;1864(5 Pt B):1968–83.

    Article  CAS  PubMed  Google Scholar 

  18. Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem. 2000;69:145–82.

    Article  CAS  PubMed  Google Scholar 

  19. Kirkby NS, Chan MV, Zaiss AK, Garcia-Vaz E, Jiao J, Berglund LM, et al. Systematic study of constitutive cyclooxygenase-2 expression: role of NF-kappaB and NFAT transcriptional pathways. Proc Natl Acad Sci U S A. 2016;113(2):434–9.

    Article  CAS  PubMed  Google Scholar 

  20. Kirkby NS, Zaiss AK, Urquhart P, Jiao J, Austin PJ, Al-Yamani M, et al. LC-MS/MS confirms that COX-1 drives vascular prostacyclin whilst gene expression pattern reveals non-vascular sites of COX-2 expression. PLoS One. 2013;8(7):e69524.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Therland KL, Stubbe J, Thiesson HC, Ottosen PD, Walter S, Sorensen GL, et al. Cycloxygenase-2 is expressed in vasculature of normal and ischemic adult human kidney and is colocalized with vascular prostaglandin E2 EP4 receptors. J Am Soc Nephrol. 2004;15(5):1189–98.

    Article  CAS  PubMed  Google Scholar 

  22. Spencer AG, Woods JW, Arakawa T, Singer II, Smith WL. Subcellular localization of prostaglandin endoperoxide H synthases-1 and -2 by immunoelectron microscopy. J Biol Chem. 1998;273(16):9886–93.

    Article  CAS  PubMed  Google Scholar 

  23. Yuan C, Smith WL. A cyclooxygenase-2-dependent prostaglandin E2 biosynthetic system in the Golgi apparatus. J Biol Chem. 2015;290(9):5606–20.

    Article  CAS  PubMed  Google Scholar 

  24. Caligiuri SP, Love K, Winter T, Gauthier J, Taylor CG, Blydt-Hansen T, et al. Dietary linoleic acid and alpha-linolenic acid differentially affect renal oxylipins and phospholipid fatty acids in diet-induced obese rats. J Nutr. 2013;143(9):1421–31.

    Article  CAS  PubMed  Google Scholar 

  25. Schuchardt JP, Schmidt S, Kressel G, Dong H, Willenberg I, Hammock BD, et al. Comparison of free serum oxylipin concentrations in hyper- vs. normolipidemic men. Prostaglandins Leukot Essent Fatty Acids. 2013;89(1):19–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Psychogios N, Hau DD, Peng J, Guo AC, Mandal R, Bouatra S, et al. The human serum metabolome. PLoS One. 2011;6(2):e16957.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Funk CD, Powell WS. Metabolism of linoleic acid by prostaglandin endoperoxide synthase from adult and fetal blood vessels. Biochim Biophys Acta. 1983;754(1):57–71.

    Article  CAS  PubMed  Google Scholar 

  28. Laneuville O, Breuer DK, Xu N, Huang ZH, Gage DA, Watson JT, et al. Fatty acid substrate specificities of human prostaglandin-endoperoxide H synthase-1 and -2. Formation of 12-hydroxy-(9Z, 13E/Z, 15Z)- octadecatrienoic acids from alpha-linolenic acid. J Biol Chem. 1995;270(33):19330–6.

    Article  CAS  PubMed  Google Scholar 

  29. Coleman RA, Grix SP, Head SA, Louttit JB, Mallett A, Sheldrick RL. A novel inhibitory prostanoid receptor in piglet saphenous vein. Prostaglandins. 1994;47(2):151–68.

    Article  CAS  PubMed  Google Scholar 

  30. Wuest SJ, Crucet M, Gemperle C, Loretz C, Hersberger M. Expression and regulation of 12/15-lipoxygenases in human primary macrophages. Atherosclerosis. 2012;225(1):121–7.

    Article  CAS  PubMed  Google Scholar 

  31. Lepley RA, Fitzpatrick FA. Irreversible inactivation of 5-lipoxygenase by leukotriene A4. Characterization of product inactivation with purified enzyme and intact leukocytes. J Biol Chem. 1994;269(4):2627–31.

    Article  CAS  PubMed  Google Scholar 

  32. Forsell PK, Brunnstrom A, Johannesson M, Claesson HE. Metabolism of anandamide into eoxamides by 15-lipoxygenase-1 and glutathione transferases. Lipids. 2012;47(8):781–91.

    Article  CAS  PubMed  Google Scholar 

  33. Huang LS, Kang JS, Kim MR, Sok DE. Oxygenation of arachidonoyl lysophospholipids by lipoxygenases from soybean, porcine leukocyte, or rabbit reticulocyte. J Agric Food Chem. 2008;56(4):1224–32.

    Article  CAS  PubMed  Google Scholar 

  34. Schewe T, Halangk W, Hiebsch C, Rapoport SM. A lipoxygenase in rabbit reticulocytes which attacks phospholipids and intact mitochondria. FEBS Lett. 1975;60(1):149–52.

    Article  CAS  PubMed  Google Scholar 

  35. Hutchins PM, Murphy RC. Cholesteryl ester acyl oxidation and remodeling in murine macrophages: formation of oxidized phosphatidylcholine. J Lipid Res. 2012;53(8):1588–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Belkner J, Wiesner R, Rathman J, Barnett J, Sigal E, Kuhn H. Oxygenation of lipoproteins by mammalian lipoxygenases. Eur J Biochem. 1993;213(1):251–61.

    Article  CAS  PubMed  Google Scholar 

  37. Shoieb SM, El-Sherbeni AA, El-Kadi AOS. Subterminal hydroxyeicosatetraenoic acids: crucial lipid mediators in normal physiology and disease states. Chem Biol Interact. 2019;299:140–50.

    Article  CAS  PubMed  Google Scholar 

  38. Natarajan R, Bai W, Rangarajan V, Gonzales N, Gu JL, Lanting L, et al. Platelet-derived growth factor BB mediated regulation of 12-lipoxygenase in porcine aortic smooth muscle cells. J Cell Physiol. 1996;169(2):391–400.

    Article  CAS  PubMed  Google Scholar 

  39. Natarajan R, Gu JL, Rossi J, Gonzales N, Lanting L, Xu L, et al. Elevated glucose and angiotensin II increase 12-lipoxygenase activity and expression in porcine aortic smooth muscle cells. Proc Natl Acad Sci U S A. 1993;90(11):4947–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Conrad DJ, Kuhn H, Mulkins M, Highland E, Sigal E. Specific inflammatory cytokines regulate the expression of human monocyte 15-lipoxygenase. Proc Natl Acad Sci U S A. 1992;89(1):217–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Maayah ZH, El-Kadi AO. The role of mid-chain hydroxyeicosatetraenoic acids in the pathogenesis of hypertension and cardiac hypertrophy. Arch Toxicol. 2016;90(1):119–36.

    Article  CAS  PubMed  Google Scholar 

  42. Takai S, Jin D, Kirimura K, Fujimoto Y, Miyazaki M. 12-Hydroxyeicosatetraenoic acid potentiates angiotensin II-induced pressor response in rats. Eur J Pharmacol. 2001;418(1–2):R1–2.

    Article  CAS  PubMed  Google Scholar 

  43. Yiu SS, Zhao X, Inscho EW, Imig JD. 12-Hydroxyeicosatetraenoic acid participates in angiotensin II afferent arteriolar vasoconstriction by activating L-type calcium channels. J Lipid Res. 2003;44(12):2391–9.

    Article  CAS  PubMed  Google Scholar 

  44. Nadler JL, Natarajan R, Stern N. Specific action of the lipoxygenase pathway in mediating angiotensin II-induced aldosterone synthesis in isolated adrenal glomerulosa cells. J Clin Invest. 1987;80(6):1763–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Stern N, Golub M, Nozawa K, Berger M, Knoll E, Yanagawa N, et al. Selective inhibition of angiotensin II-mediated vasoconstriction by lipoxygenase blockade. Am J Phys. 1989;257(2 Pt 2):H434–43.

    CAS  Google Scholar 

  46. Zhang L, Li Y, Chen M, Su X, Yi D, Lu P, et al. 15-LO/15-HETE mediated vascular adventitia fibrosis via p38 MAPK-dependent TGF-beta. J Cell Physiol. 2014;229(2):245–57.

    Article  CAS  PubMed  Google Scholar 

  47. Wallukat G, Morwinski R, Kuhn H. Modulation of the beta-adrenergic response of cardiomyocytes by specific lipoxygenase products involves their incorporation into phosphatidylinositol and activation of protein kinase C. J Biol Chem. 1994;269(46):29055–60.

    Article  CAS  PubMed  Google Scholar 

  48. Levick SP, Loch DC, Taylor SM, Janicki JS. Arachidonic acid metabolism as a potential mediator of cardiac fibrosis associated with inflammation. J Immunol. 2007;178(2):641–6.

    Article  CAS  PubMed  Google Scholar 

  49. Kayama Y, Minamino T, Toko H, Sakamoto M, Shimizu I, Takahashi H, et al. Cardiac 12/15 lipoxygenase-induced inflammation is involved in heart failure. J Exp Med. 2009;206(7):1565–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Maayah ZH, Althurwi HN, Abdelhamid G, Lesyk G, Jurasz P, El-Kadi AO. CYP1B1 inhibition attenuates doxorubicin-induced cardiotoxicity through a mid-chain HETEs-dependent mechanism. Pharmacol Res. 2016;105:28–43.

    Article  CAS  PubMed  Google Scholar 

  51. Kong EK, Yu S, Sanderson JE, Chen KB, Huang Y, Yu CM. A novel anti-fibrotic agent, baicalein, for the treatment of myocardial fibrosis in spontaneously hypertensive rats. Eur J Pharmacol. 2011;658(2–3):175–81.

    Article  CAS  PubMed  Google Scholar 

  52. Buckley CD, Gilroy DW, Serhan CN. Proresolving lipid mediators and mechanisms in the resolution of acute inflammation. Immunity. 2014;40(3):315–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kramer HJ, Stevens J, Grimminger F, Seeger W. Fish oil fatty acids and human platelets: dose-dependent decrease in dienoic and increase in trienoic thromboxane generation. Biochem Pharmacol. 1996;52(8):1211–7.

    Article  CAS  PubMed  Google Scholar 

  54. Honn KV, Nelson KK, Renaud C, Bazaz R, Diglio CA, Timar J. Fatty acid modulation of tumor cell adhesion to microvessel endothelium and experimental metastasis. Prostaglandins. 1992;44(5):413–29.

    Article  CAS  PubMed  Google Scholar 

  55. Folcik VA, Cathcart MK. Predominance of esterified hydroperoxy-linoleic acid in human monocyte-oxidized LDL. J Lipid Res. 1994;35(9):1570–82.

    Article  CAS  PubMed  Google Scholar 

  56. Hattori T, Obinata H, Ogawa A, Kishi M, Tatei K, Ishikawa O, et al. G2A plays proinflammatory roles in human keratinocytes under oxidative stress as a receptor for 9-hydroxyoctadecadienoic acid. J Invest Dermatol. 2008;128(5):1123–33.

    Article  CAS  PubMed  Google Scholar 

  57. Obinata H, Izumi T. G2A as a receptor for oxidized free fatty acids. Prostaglandins Other Lipid Mediat. 2009;89(3–4):66–72.

    Article  CAS  PubMed  Google Scholar 

  58. Kwon SY, Massey K, Watson MA, Hussain T, Volpe G, Buckley CD, et al. Oxidised metabolites of the omega-6 fatty acid linoleic acid activate dFOXO. Life Sci Alliance. 2020;3(2):e201900356.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Theken KN, Schuck RN, Edin ML, Tran B, Ellis K, Bass A, et al. Evaluation of cytochrome P450-derived eicosanoids in humans with stable atherosclerotic cardiovascular disease. Atherosclerosis. 2012;222(2):530–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Buchanan MR, Haas TA, Lagarde M, Guichardant M. 13-Hydroxyoctadecadienoic acid is the vessel wall chemorepellant factor, LOX. J Biol Chem. 1985;260(30):16056–9.

    Article  CAS  PubMed  Google Scholar 

  61. Tloti MA, Moon DG, Weston LK, Kaplan JE. Effect of 13-hydroxyoctadeca-9,11-dienoic acid (13-HODE) on thrombin induced platelet adherence to endothelial cells in vitro. Thromb Res. 1991;62(4):305–17.

    Article  CAS  PubMed  Google Scholar 

  62. Stoll LL, Morland MR, Spector AA. 13-HODE increases intracellular calcium in vascular smooth muscle cells. Am J Phys. 1994;266(4 Pt 1):C990–6.

    Article  CAS  Google Scholar 

  63. De Meyer GR, Bult H, Verbeuren TJ, Herman AG. The role of endothelial cells in the relaxations induced by 13-hydroxy- and 13-hydroperoxylinoleic acid in canine arteries. Br J Pharmacol. 1992;107(2):597–603.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Iversen L, Fogh K, Bojesen G, Kragballe K. Linoleic acid and dihomogammalinolenic acid inhibit leukotriene B4 formation and stimulate the formation of their 15-lipoxygenase products by human neutrophils in vitro. Evidence of formation of antiinflammatory compounds. Agents Actions. 1991;33(3–4):286–91.

    Article  CAS  PubMed  Google Scholar 

  65. Murthy S, Born E, Mathur S, Field FJ. 13-Hydroxy octadecadienoic acid (13-HODE) inhibits triacylglycerol-rich lipoprotein secretion by CaCo-2 cells. J Lipid Res. 1998;39(6):1254–62.

    Article  CAS  PubMed  Google Scholar 

  66. Zhang Z, Emami S, Hennebelle M, Morgan RK, Lerno LA, Slupsky CM, et al. Linoleic acid-derived 13-hydroxyoctadecadienoic acid is absorbed and incorporated into rat tissues. Biochim Biophys Acta Mol Cell Biol Lipids. 1866;2021(3):158870.

    Google Scholar 

  67. Fang X, Kaduce TL, Spector AA. 13-(S)-hydroxyoctadecadienoic acid (13-HODE) incorporation and conversion to novel products by endothelial cells. J Lipid Res. 1999;40(4):699–707.

    Article  CAS  PubMed  Google Scholar 

  68. Ramsden CE, Ringel A, Feldstein AE, Taha AY, MacIntosh BA, Hibbeln JR, et al. Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans. Prostaglandins Leukot Essent Fatty Acids. 2012;87(4–5):135–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Shureiqi I, Wojno KJ, Poore JA, Reddy RG, Moussalli MJ, Spindler SA, et al. Decreased 13-S-hydroxyoctadecadienoic acid levels and 15-lipoxygenase-1 expression in human colon cancers. Carcinogenesis. 1999;20(10):1985–95.

    Article  CAS  PubMed  Google Scholar 

  70. Ziboh VA, Miller CC, Cho Y. Significance of lipoxygenase-derived monohydroxy fatty acids in cutaneous biology. Prostaglandins Other Lipid Mediat. 2000;63(1–2):3–13.

    Article  CAS  PubMed  Google Scholar 

  71. Brash AR, Boeglin WE, Capdevila JH, Yeola S, Blair IA. 7-HETE, 10-HETE, and 13-HETE are major products of NADPH-dependent arachidonic acid metabolism in rat liver microsomes: analysis of their stereochemistry, and the stereochemistry of their acid-catalyzed rearrangement. Arch Biochem Biophys. 1995;321(2):485–92.

    Article  CAS  PubMed  Google Scholar 

  72. Oliw EH. bis-Allylic hydroxylation of linoleic acid and arachidonic acid by human hepatic monooxygenases. Biochim Biophys Acta. 1993;1166(2–3):258–63.

    Article  CAS  PubMed  Google Scholar 

  73. Laethem RM, Balazy M, Falck JR, Laethem CL, Koop DR. Formation of 19(S)-, 19(R)-, and 18(R)-hydroxyeicosatetraenoic acids by alcohol-inducible cytochrome P450 2E1. J Biol Chem. 1993;268(17):12912–8.

    Article  CAS  PubMed  Google Scholar 

  74. Nebert DW, Wikvall K, Miller WL. Human cytochromes P450 in health and disease. Philos Trans R Soc Lond Ser B Biol Sci. 2013;368(1612):20120431.

    Article  CAS  Google Scholar 

  75. Wu CC, Gupta T, Garcia V, Ding Y, Schwartzman ML. 20-HETE and blood pressure regulation: clinical implications. Cardiol Rev. 2014;22(1):1–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Spector AA, Kim HY. Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism. Biochim Biophys Acta. 2015;1851(4):356–65.

    Article  CAS  PubMed  Google Scholar 

  77. Bednar MM, Gross CE, Balazy MK, Belosludtsev Y, Colella DT, Falck JR, et al. 16(R)-hydroxy-5,8,11,14-eicosatetraenoic acid, a new arachidonate metabolite in human polymorphonuclear leukocytes. Biochem Pharmacol. 2000;60(3):447–55.

    Article  CAS  PubMed  Google Scholar 

  78. Reddy YK, Reddy LM, Capdevila JH, Falck JR. Practical, asymmetric synthesis of 16-hydroxyeicosa-5(Z),8(Z), 11(Z),14(Z)-tetraenoic acid (16-HETE), an endogenous inhibitor of neutrophil activity. Bioorg Med Chem Lett. 2003;13(21):3719–20.

    Article  CAS  PubMed  Google Scholar 

  79. Zhu Y, Schieber EB, McGiff JC, Balazy M. Identification of arachidonate P-450 metabolites in human platelet phospholipids. Hypertension. 1995;25(4 Pt 2):854–9.

    Article  CAS  PubMed  Google Scholar 

  80. Maciejewska D, Ossowski P, Drozd A, Ryterska K, Jamiol-Milc D, Banaszczak M, et al. Metabolites of arachidonic acid and linoleic acid in early stages of non-alcoholic fatty liver disease--a pilot study. Prostaglandins Other Lipid Mediat. 2015;121(Pt B):184–9.

    Article  CAS  PubMed  Google Scholar 

  81. Carroll MA, Balazy M, Huang DD, Rybalova S, Falck JR, McGiff JC. Cytochrome P450-derived renal HETEs: storage and release. Kidney Int. 1997;51(6):1696–702.

    Article  CAS  PubMed  Google Scholar 

  82. Wang W, Lu M. Effect of arachidonic acid on activity of the apical K+ channel in the thick ascending limb of the rat kidney. J Gen Physiol. 1995;106(4):727–43.

    Article  CAS  PubMed  Google Scholar 

  83. Chadderdon SM, Belcik JT, Bader L, Kievit P, Grove KL, Lindner JR. Vasoconstrictor eicosanoids and impaired microvascular function in inactive and insulin-resistant primates. Int J Obes. 2016;40(10):1600–3.

    Article  CAS  Google Scholar 

  84. Zhang F, Deng H, Kemp R, Singh H, Gopal VR, Falck JR, et al. Decreased levels of cytochrome P450 2E1-derived eicosanoids sensitize renal arteries to constrictor agonists in spontaneously hypertensive rats. Hypertension. 2005;45(1):103–8.

    Article  CAS  PubMed  Google Scholar 

  85. El-Sherbeni AA, El-Kadi AO. Alterations in cytochrome P450-derived arachidonic acid metabolism during pressure overload-induced cardiac hypertrophy. Biochem Pharmacol. 2014;87(3):456–66.

    Article  CAS  PubMed  Google Scholar 

  86. El-Sherbeni AA, El-Kadi AO. Characterization of arachidonic acid metabolism by rat cytochrome P450 enzymes: the involvement of CYP1As. Drug Metab Dispos. 2014;42(9):1498–507.

    Article  PubMed  CAS  Google Scholar 

  87. Poloyac SM, Tortorici MA, Przychodzin DI, Reynolds RB, Xie W, Frye RF, et al. The effect of isoniazid on CYP2E1- and CYP4A-mediated hydroxylation of arachidonic acid in the rat liver and kidney. Drug Metab Dispos. 2004;32(7):727–33.

    Article  CAS  PubMed  Google Scholar 

  88. Capdevila JH, Falck JR, Harris RC. Cytochrome P450 and arachidonic acid bioactivation. Molecular and functional properties of the arachidonate monooxygenase. J Lipid Res. 2000;41(2):163–81.

    Article  CAS  PubMed  Google Scholar 

  89. Cheng J, Ou JS, Singh H, Falck JR, Narsimhaswamy D, Pritchard KA Jr, et al. 20-Hydroxyeicosatetraenoic acid causes endothelial dysfunction via eNOS uncoupling. Am J Physiol Heart Circ Physiol. 2008;294(2):H1018–26.

    Article  CAS  PubMed  Google Scholar 

  90. Alonso-Galicia M, Falck JR, Reddy KM, Roman RJ. 20-HETE agonists and antagonists in the renal circulation. Am J Phys. 1999;277(5):F790–6.

    CAS  Google Scholar 

  91. Roman RJ. P-450 metabolites of arachidonic acid in the control of cardiovascular function. Physiol Rev. 2002;82(1):131–85.

    Article  CAS  PubMed  Google Scholar 

  92. Nayeem MA, Zeldin DC, Boegehold MA, Morisseau C, Marowsky A, Ponnoth DS, et al. Modulation by salt intake of the vascular response mediated through adenosine A(2A) receptor: role of CYP epoxygenase and soluble epoxide hydrolase. Am J Physiol Regul Integr Comp Physiol. 2010;299(1):R325–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Nayeem MA, Zeldin DC, Boegehold MA, Falck JR. Salt modulates vascular response through adenosine A(2A) receptor in eNOS-null mice: role of CYP450 epoxygenase and soluble epoxide hydrolase. Mol Cell Biochem. 2011;350(1–2):101–11.

    Article  CAS  PubMed  Google Scholar 

  94. Nayeem MA, Ponnoth DS, Boegehold MA, Zeldin DC, Falck JR, Mustafa SJ. High-salt diet enhances mouse aortic relaxation through adenosine A2A receptor via CYP epoxygenases. Am J Physiol Regul Integr Comp Physiol. 2009;296(3):R567–74.

    Article  CAS  PubMed  Google Scholar 

  95. Nayeem MA, Poloyac SM, Falck JR, Zeldin DC, Ledent C, Ponnoth DS, et al. Role of CYP epoxygenases in A2A AR-mediated relaxation using A2A AR-null and wild-type mice. Am J Physiol Heart Circ Physiol. 2008;295(5):H2068–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Miyata N, Roman RJ. Role of 20-hydroxyeicosatetraenoic acid (20-HETE) in vascular system. J Smooth Muscle Res. 2005;41(4):175–93.

    Article  PubMed  Google Scholar 

  97. Spector AA. Arachidonic acid cytochrome P450 epoxygenase pathway. J Lipid Res. 2009;50(Suppl):S52–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Bellien J, Joannides R. Epoxyeicosatrienoic acid pathway in human health and diseases. J Cardiovasc Pharmacol. 2013;61(3):188–96.

    Article  CAS  PubMed  Google Scholar 

  99. Wang D, Dubois RN. Epoxyeicosatrienoic acids: a double-edged sword in cardiovascular diseases and cancer. J Clin Invest. 2012;122(1):19–22.

    Article  PubMed  CAS  Google Scholar 

  100. Weintraub NL, Fang X, Kaduce TL, VanRollins M, Chatterjee P, Spector AA. Epoxide hydrolases regulate epoxyeicosatrienoic acid incorporation into coronary endothelial phospholipids. Am J Phys. 1999;277(5):H2098–108.

    CAS  Google Scholar 

  101. Shahabi P, Siest G, Meyer UA, Visvikis-Siest S. Human cytochrome P450 epoxygenases: variability in expression and role in inflammation-related disorders. Pharmacol Ther. 2014;144(2):134–61.

    Article  CAS  PubMed  Google Scholar 

  102. Fleming I. Vascular cytochrome p450 enzymes: physiology and pathophysiology. Trends Cardiovasc Med. 2008;18(1):20–5.

    Article  CAS  PubMed  Google Scholar 

  103. Deng Y, Theken KN, Lee CR. Cytochrome P450 epoxygenases, soluble epoxide hydrolase, and the regulation of cardiovascular inflammation. J Mol Cell Cardiol. 2010;48(2):331–41.

    Article  CAS  PubMed  Google Scholar 

  104. Seubert J, Yang B, Bradbury JA, Graves J, Degraff LM, Gabel S, et al. Enhanced postischemic functional recovery in CYP2J2 transgenic hearts involves mitochondrial ATP-sensitive K+ channels and p42/p44 MAPK pathway. Circ Res. 2004;95(5):506–14.

    Article  CAS  PubMed  Google Scholar 

  105. Wang X, Ni L, Yang L, Duan Q, Chen C, Edin ML, et al. CYP2J2-derived epoxyeicosatrienoic acids suppress endoplasmic reticulum stress in heart failure. Mol Pharmacol. 2014;85(1):105–15.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Lee CR, North KE, Bray MS, Couper DJ, Heiss G, Zeldin DC. CYP2J2 and CYP2C8 polymorphisms and coronary heart disease risk: the Atherosclerosis Risk in Communities (ARIC) study. Pharmacogenet Genomics. 2007;17(5):349–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Lee CR, North KE, Bray MS, Fornage M, Seubert JM, Newman JW, et al. Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study. Hum Mol Genet. 2006;15(10):1640–9.

    Article  CAS  PubMed  Google Scholar 

  108. Thompson DA, Hammock BD. Dihydroxyoctadecamonoenoate esters inhibit the neutrophil respiratory burst. J Biosci. 2007;32(2):279–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Pinckard KM, Shettigar VK, Wright KR, Abay E, Baer LA, Vidal P, et al. A novel endocrine role for the BAT-released lipokine 12,13-diHOME to mediate cardiac function. Circulation. 2021;143(2):145–59.

    Article  CAS  PubMed  Google Scholar 

  110. Lynes MD, Leiria LO, Lundh M, Bartelt A, Shamsi F, Huang TL, et al. The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue. Nat Med. 2017;23(5):631–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Stanford KI, Lynes MD, Takahashi H, Baer LA, Arts PJ, May FJ, et al. 12,13-diHOME: an exercise-induced lipokine that increases skeletal muscle fatty acid uptake. Cell Metab. 2018;27(5):1111–20. e3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Gollasch B, Dogan I, Rothe M, Gollasch M, Luft FC. Maximal exercise and plasma cytochrome P450 and lipoxygenase mediators: a lipidomics study. Physiol Rep. 2019;7(13):e14165.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Hernandez-Saavedra D, Stanford KI. The regulation of lipokines by environmental factors. Nutrients. 2019;11(10):2422.

    Article  CAS  PubMed Central  Google Scholar 

  114. Edwards LM, Lawler NG, Nikolic SB, Peters JM, Horne J, Wilson R, et al. Metabolomics reveals increased isoleukotoxin diol (12,13-DHOME) in human plasma after acute Intralipid infusion. J Lipid Res. 2012;53(9):1979–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Totani Y, Saito Y, Ishizaki T, Sasaki F, Ameshima S, Miyamori I. Leukotoxin and its diol induce neutrophil chemotaxis through signal transduction different from that of fMLP. Eur Respir J. 2000;15(1):75–9.

    Article  CAS  PubMed  Google Scholar 

  116. Viswanathan S, Hammock BD, Newman JW, Meerarani P, Toborek M, Hennig B. Involvement of CYP 2C9 in mediating the proinflammatory effects of linoleic acid in vascular endothelial cells. J Am Coll Nutr. 2003;22(6):502–10.

    Article  CAS  PubMed  Google Scholar 

  117. Lecka-Czernik B, Moerman EJ, Grant DF, Lehmann JM, Manolagas SC, Jilka RL. Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation. Endocrinology. 2002;143(6):2376–84.

    Article  CAS  PubMed  Google Scholar 

  118. Markaverich BM, Crowley JR, Alejandro MA, Shoulars K, Casajuna N, Mani S, et al. Leukotoxin diols from ground corncob bedding disrupt estrous cyclicity in rats and stimulate MCF-7 breast cancer cell proliferation. Environ Health Perspect. 2005;113(12):1698–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Fromel T, Jungblut B, Hu J, Trouvain C, Barbosa-Sicard E, Popp R, et al. Soluble epoxide hydrolase regulates hematopoietic progenitor cell function via generation of fatty acid diols. Proc Natl Acad Sci U S A. 2012;109(25):9995–10000.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Eskander MA, Ruparel S, Green DP, Chen PB, Por ED, Jeske NA, et al. Persistent nociception triggered by nerve growth factor (NGF) is mediated by TRPV1 and oxidative mechanisms. J Neurosci. 2015;35(22):8593–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Sisignano M, Angioni C, Park CK, Meyer Dos Santos S, Jordan H, Kuzikov M, et al. Targeting CYP2J to reduce paclitaxel-induced peripheral neuropathic pain. Proc Natl Acad Sci U S A. 2016;113(44):12544–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Zimmer B, Angioni C, Osthues T, Toewe A, Thomas D, Pierre SC, et al. The oxidized linoleic acid metabolite 12,13-DiHOME mediates thermal hyperalgesia during inflammatory pain. Biochim Biophys Acta Mol Cell Biol Lipids. 2018;1863(7):669–78.

    Article  CAS  PubMed  Google Scholar 

  123. Samokhvalov V, Jamieson KL, Darwesh AM, Keshavarz-Bahaghighat H, Lee TYT, Edin M, et al. Deficiency of soluble epoxide hydrolase protects cardiac function impaired by LPS-induced acute inflammation. Front Pharmacol. 2018;9:1572.

    Article  CAS  PubMed  Google Scholar 

  124. Bays HE, Toth PP, Kris-Etherton PM, Abate N, Aronne LJ, Brown WV, et al. Obesity, adiposity, and dyslipidemia: a consensus statement from the National Lipid Association. J Clin Lipidol. 2013;7(4):304–83.

    Article  PubMed  Google Scholar 

  125. Cercato C, Fonseca FA. Cardiovascular risk and obesity. Diabetol Metab Syndr. 2019;11:74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Howard BV, Ruotolo G, Robbins DC. Obesity and dyslipidemia. Endocrinol Metab Clin N Am. 2003;32(4):855–67.

    Article  CAS  Google Scholar 

  127. Wang W, Yang J, Qi W, Yang H, Wang C, Tan B, et al. Lipidomic profiling of high-fat diet-induced obesity in mice: importance of cytochrome P450-derived fatty acid epoxides. Obesity (Silver Spring). 2017;25(1):132–40.

    Article  CAS  Google Scholar 

  128. Platt C, Houstis N, Rosenzweig A. Using exercise to measure and modify cardiac function. Cell Metab. 2015;21(2):227–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Roh J, Rhee J, Chaudhari V, Rosenzweig A. The role of exercise in cardiac aging: from physiology to molecular mechanisms. Circ Res. 2016;118(2):279–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Nieman DC, Shanely RA, Luo B, Meaney MP, Dew DA, Pappan KL. Metabolomics approach to assessing plasma 13- and 9-hydroxy-octadecadienoic acid and linoleic acid metabolite responses to 75-km cycling. Am J Physiol Regul Integr Comp Physiol. 2014;307(1):R68–74.

    Article  CAS  PubMed  Google Scholar 

  131. Nieman DC, Shanely RA, Gillitt ND, Pappan KL, Lila MA. Serum metabolic signatures induced by a three-day intensified exercise period persist after 14 h of recovery in runners. J Proteome Res. 2013;12(10):4577–84.

    Article  CAS  PubMed  Google Scholar 

  132. Peres Valgas da Silva C, Hernandez-Saavedra D, White JD, Stanford KI. Cold and exercise: therapeutic tools to activate brown adipose tissue and combat obesity. Biology (Basel). 2019;8(1):9.

    Google Scholar 

  133. Gavalda-Navarro A, Villarroya J, Cereijo R, Giralt M, Villarroya F. The endocrine role of brown adipose tissue: an update on actors and actions. Rev Endocr Metab Disord. 2022;23(1):31–41.

    Article  CAS  PubMed  Google Scholar 

  134. Becher T, Palanisamy S, Kramer DJ, Eljalby M, Marx SJ, Wibmer AG, et al. Brown adipose tissue is associated with cardiometabolic health. Nat Med. 2021;27(1):58–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Diego Hernandez-Saavedra & Kristin I. Stanford

  2. Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, OH, USA

    Diego Hernandez-Saavedra & Kristin I. Stanford

  3. Department of Internal Medicine, Ohio State University College of Medicine, Columbus, OH, USA

    Kristin I. Stanford

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  1. Diego Hernandez-Saavedra
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  2. Kristin I. Stanford
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Correspondence to Kristin I. Stanford .

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  1. Division of Pulmonary, Critical Care, and Sleep Medicine Department of Internal Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Narasimham L. Parinandi

  2. Departments of Biomedical Engineering and Internal Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA

    Thomas J. Hund

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Hernandez-Saavedra, D., Stanford, K.I. (2022). Lipid Mediators in Cardiovascular Physiology and Disease. In: Parinandi, N.L., Hund, T.J. (eds) Cardiovascular Signaling in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-031-08309-9_8

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