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Exercise and vascular function in sedentary lifestyles in humans

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Abstract

People with sedentary lifestyles engage in minimal or no physical activity. A sedentary lifestyle promotes dysregulation of cellular redox balance, diminishes mitochondrial function, and increases NADPH oxidase activity. These changes collectively increase cellular oxidative stress, which alters endothelial function by oxidizing LDL-C, reducing NO production, and causing eNOS uncoupling. Reduced levels of nitric oxide (NO) leads to vasoconstriction, vascular remodeling, and vascular inflammation. Exercise modulates reactive oxygen species (ROS) to modify NRF2-KEAP signaling, leading to the activation of NRF2 to alleviate oxidative stress. While regular moderate exercise activates NRF2 through ROS production, high-intensity intermittent exercise stimulates NRF2 activation to a greater degree by reducing KEAP levels, which can be more beneficial for sedentary individuals. We review the damaging effects of a sedentary lifestyle on the vascular system and the health benefits of regular and intermittent exercise.

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References

  1. Andreyev AY, Kushnareva YE, Starkov AA (2005) Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc) 70(2):200–214. https://doi.org/10.1007/s10541-005-0102-7

    Article  CAS  PubMed  Google Scholar 

  2. Balady GJ, Williams MA, Ades PA, Bittner V, Comoss P, Foody JM, Franklin B, Sanderson B, Southard D (2007) Core components of cardiac rehabilitation/secondary prevention programs: 2007 update: a scientific statement from the American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee, the Council on Clinical Cardiology; the Councils on Cardiovascular Nursing, Epidemiology and Prevention, and Nutrition, Physical Activity, and Metabolism; and the American Association of Cardiovascular and Pulmonary Rehabilitation. Circulation 115(20):2675–2682. https://doi.org/10.1161/CIRCULATIONAHA.106.180945

    Article  PubMed  Google Scholar 

  3. Balasaheb Nimse S, Pal D (2015) Free radicals, natural antioxidants, and their reaction mechanisms. RSC Adv 5(35):27986–28006. https://doi.org/10.1039/C4RA13315C

    Article  CAS  Google Scholar 

  4. Baltieri N, Guizoni DM, Victorio JA, Davel AP (2018) Protective Role of Perivascular Adipose Tissue in Endothelial Dysfunction and Insulin-Induced Vasodilatation of Hypercholesterolemic LDL Receptor-Deficient Mice. Front Physiol 9:229. https://doi.org/10.3389/fphys.2018.00229

    Article  PubMed  PubMed Central  Google Scholar 

  5. Bauersachs J, Schäfer A (2015) Tetrahydrobiopterin and eNOS dimer/monomer ratio–a clue to eNOS uncoupling in diabetes? Cardiovasc Res 65(4):768–769. https://doi.org/10.1016/j.cardiores.2004.12.011

    Article  CAS  Google Scholar 

  6. Bellettiere J, Healy GN, LaMonte MJ, Kerr J (2019) Sedentary Behavior and Prevalent Diabetes in 6,166 Older Women: The Objective Physical Activity and Cardiovascular Health Study. J Gerontol A Biol Sci Med Sci 74(3):387–395. https://doi.org/10.1093/gerona/gly101

    Article  PubMed  Google Scholar 

  7. Bento-Pereira C, Dinkova-Kostova AT (2021) Activation of transcription factor Nrf2 to counteract mitochondrial dysfunction in Parkinson’s disease. Med Res Rev 41(2):785–802. https://doi.org/10.1002/med.21714

    Article  PubMed  Google Scholar 

  8. Bhatti JS, Bhatti GK, Reddy PH (2017) Mitochondrial dysfunction and oxidative stress in metabolic disorders — A step towards mitochondria based therapeutic strategies. Biochim et Biophys Acta (BBA) Molec Basis Dis 1863(5):1066–1077. https://doi.org/10.1016/j.bbadis.2016.11.010

  9. Boa SBC, Yudkin JS, Bouskela E, Eringa EC (2017) Exercise effects on perivascular adipose tissue: Endocrine and paracrine determinants of vascular function. British J Pharmacol 174(20):3466–3481. https://doi.org/10.1111/bph.13732

    Article  CAS  Google Scholar 

  10. Briones AM, Touyz RM (2019) Moderate Exercise Decreases Inflammation and Oxidative Stress in Hypertension. Hypertension 54(6):1206–1208. https://doi.org/10.1161/HYPERTENSIONAHA.109.136622

    Article  CAS  Google Scholar 

  11. de Brito FCF (2015) Inhibition of inflammatory pathways promotes an improving effect on endothelial dysfunction: The effects of Longxuetongluo capsule in an experimental model of atherosclerosis. Atherosclerosis 255:111–112. https://doi.org/10.1016/j.atherosclerosis.2016.10.040

    Article  CAS  Google Scholar 

  12. Brown NK, Zhou Z, Zhang J, Zeng R, Wu J, Eitzman DT, Chen YE, Chang L (2014) Perivascular adipose tissue in vascular function and disease: a review of current research and animal models. Arterioscler Thromb Vasc Biol 34(8):1621–1630. https://doi.org/10.1161/ATVBAHA.114.303029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bulua AC, Simon A, Maddipati R, Pelletier M, Park H, Kim KY, Sack MN, Kastner DL, Siegel RM (2011) Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS). J Exp Med 208(3):519–33. https://doi.org/10.1084/jem.20102049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cai H, Harrison DG (2000) Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 87(10):840–844. https://doi.org/10.1161/01.res.87.10.840

    Article  CAS  PubMed  Google Scholar 

  15. Cai S, Khoo J, Channon KM (2005) Augmented BH4 by gene transfer restores nitric oxide synthase function in hyperglycemic human endothelial cells. Cardiovasc Res 65(4):823–831. https://doi.org/10.1016/j.cardiores.2004.10.040

    Article  CAS  PubMed  Google Scholar 

  16. Chatterjee S (2018) Endothelial Mechanotransduction, Redox Signaling and the Regulation of Vascular Inflammatory Pathways. Front Physiol 9:524. https://doi.org/10.3389/fphys.2018.00524

    Article  PubMed  PubMed Central  Google Scholar 

  17. Chen B, Lu Y, Chen Y, Cheng J (2015) The role of Nrf2 in oxidative stress-induced endothelial injuries. J Endocrinol 225(3):R83-99. https://doi.org/10.1530/JOE-14-0662

    Article  CAS  PubMed  Google Scholar 

  18. Chen JY, Ye ZX, Wang XF, Chang J, Yang MW, Zhong HH, Hong FF, Yang SL (2018) Nitric oxide bioavailability dysfunction involves in atherosclerosis. Biomed Pharmacother 97:423–428. https://doi.org/10.1016/j.biopha.2017.10.122

    Article  CAS  PubMed  Google Scholar 

  19. Chen X, Zhu X, Wei A, Chen F, Gao Q, Lu K, Jiang Q, Cao W (2011) Nrf2 epigenetic derepression induced by running exercise protects against osteoporosis. Bone Res 9(1):1. https://doi.org/10.1038/s41413-020-00128-8

    Article  CAS  Google Scholar 

  20. Cosentino-Gomes D, Rocco-Machado N, Meyer-Fernandes JR (2012) Cell Signaling through Protein Kinase C Oxidation and Activation. Int J Mol Sci 13(9):10697–10721. https://doi.org/10.3390/ijms130910697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Crabtree MJ, Channon KM (2009) Dihydrofolate reductase and biopterin recycling in cardiovascular disease. J Mol Cell Cardiol 47(6):749–751. https://doi.org/10.1016/j.yjmcc.2009.09.011

    Article  CAS  PubMed  Google Scholar 

  22. Crabtree MJ, Smith CL, Lam G, Goligorsky MS, Gross SS (2008) Ratio of 5,6,7,8-tetrahydrobiopterin to 7,8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOS. Am J Physiol Heart Circ Physiol 294(4):H1530-1540. https://doi.org/10.1152/ajpheart.00823.2007

    Article  CAS  PubMed  Google Scholar 

  23. Cuadrado A, Rojo AI, Wells G, Hayes JD, Cousin SP, Rumsey WL, Attucks OC, Franklin S, Levonen AL, Kensler TW, Dinkova-Kostova AT (2019) Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases. Nat Rev Drug Discov 18(4):295–317. https://doi.org/10.1038/s41573-018-0008-x

    Article  CAS  PubMed  Google Scholar 

  24. Davignon J, Ganz P (2004) Role of endothelial dysfunction in atherosclerosis. Circulation 109(23):27–32. https://doi.org/10.1161/01.CIR.0000131515.03336.f8

    Article  CAS  Google Scholar 

  25. Ding WX, Yin XM (2012) Mitophagy: mechanisms, pathophysiological roles, and analysis. Biol Chem 393(7):547–564. https://doi.org/10.1515/hsz-2012-0119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Dokumacioglu E, Duzcan I, Iskender H, Sahin A (2022) RhoA/ROCK-1 Signaling Pathway and Oxidative Stress in Coronary Artery Disease Patients. Braz J Cardiovasc Surg 37(2):212–218. https://doi.org/10.21470/1678-9741-2020-0525

    Article  PubMed  PubMed Central  Google Scholar 

  27. Drew B, Phaneuf S, Dirks A, Selman C, Gredilla R, Lezza A, Barja G, Leeuwenburgh C (2003) Effects of aging and caloric restriction on mitochondrial energy production in gastrocnemius muscle and heart. Am JPhysiol-Regul Integr Comp Physiol. https://doi.org/10.1152/ajpregu.00455.2002

    Article  Google Scholar 

  28. Ehara S, Ueda M, Naruko T, Haze K, Itoh A, Otsuka M, Komatsu R, Matsuo T, Itabe H, Takano T, Tsukamoto Y, Yoshiyama M, Takeuchi K, Yoshikawa J, Becker AE (2001) Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation 103(15):1955–60. https://doi.org/10.1161/01.cir.103.15.1955

    Article  CAS  PubMed  Google Scholar 

  29. Elosua R, Molina L, Fito M, Arquer A, Sanchez-Quesada JL, Covas MI, Ordoñez-Llanos J, Marrugat J (2003) Response of oxidative stress biomarkers to a 16-week aerobic physical activity program, and to acute physical activity, in healthy young men and women. Atherosclerosis 167(2):327–334. https://doi.org/10.1016/s0021-9150(03)00018-2

    Article  CAS  PubMed  Google Scholar 

  30. Fasipe B, Li S, Laher I (2021) Harnessing the cardiovascular benefits of exercise: Are Nrf2 activators useful? Sports Medicine and Health Science 3(2):70–79. https://doi.org/10.1016/j.smhs.2021.04.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Figueiredo PA, Ferreira RM, Appell HJ, Duarte JA (2008) Age-induced morphological, biochemical, and functional alterations in isolated mitochondria from murine skeletal muscle. J Gerontol A Biol Sci Med Sci 63(4):350–359. https://doi.org/10.1093/gerona/63.4.350

    Article  PubMed  Google Scholar 

  32. Fitzgibbons TP, Kogan S, Aouadi M, Hendricks GM, Straubhaar J, Czech MP (2011) Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation. Am J Physiol Heart Circ Physiol 301(4):H1425-1437. https://doi.org/10.1152/ajpheart.00376.2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Frank S, Gaume B, Bergmann-Leitner ES, Leitner WW, Robert EG, Catez F, Smith CL, Youle RJ (2001) The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev Cell 1(4):515–525. https://doi.org/10.1016/S1534-5807(01)00055-7

    Article  CAS  PubMed  Google Scholar 

  34. Franklin BA, Eijsvogels H, TM (2023) A narrative review on exercise and cardiovascular disease: Physical activity thresholds for optimizing health outcomes. Heart Mind 7:34–39

    Article  Google Scholar 

  35. Gallo G, Volpe M, Savoia C (2022) Endothelial Dysfunction in Hypertension: Current Concepts and Clinical Implications. Front Med 8:798958. https://doi.org/10.3389/fmed.2021.798958

    Article  Google Scholar 

  36. Gan X, Huang S, Yu Q, Yu H, Yan SS (2015) Blockade of Drp1 rescues oxidative stress-induced osteoblast dysfunction. Biochem Biophys Res Commun 468(4):719–725. https://doi.org/10.1016/j.bbrc.2015.11.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Gimbrone MA, García-Cardeña G (2016) Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circ Res 118(4):620–636. https://doi.org/10.1161/CIRCRESAHA.115.306301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gliozzi M, Scicchitano M, Bosco F, Musolino V, Carresi C, Scarano F, Maiuolo J, Nucera S, Maretta A, Paone S, Mollace R, Ruga S, Zito MC, Macrì R, Oppedisano F, Palma E, Salvemini D, Muscoli C, Mollace V (2019) Modulation of Nitric Oxide Synthases by Oxidized LDLs: Role in Vascular Inflammation and Atherosclerosis Development. Int J Mol Sci 20(13):3294. https://doi.org/10.3390/ijms20133294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. González K, Fuentes J, Márquez JL (2017) Physical Inactivity, Sedentary Behavior and Chronic Diseases. Korean J Fam Med 38(3):111–115. https://doi.org/10.4082/kjfm.2017.38.3.111

    Article  PubMed  PubMed Central  Google Scholar 

  40. Gorrini C, Harris IS, Mak TW (2013) Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov 12(12):12. https://doi.org/10.1038/nrd4002

    Article  CAS  Google Scholar 

  41. Gumeni S, Papanagnou ED, Manola MS, Trougakos IP (2021) Nrf2 activation induces mitophagy and reverses Parkin/Pink1 knock down-mediated neuronal and muscle degeneration phenotypes. Cell Death Dis 12(7):671. https://doi.org/10.1038/s41419-021-03952-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Guo C, Sun L, Chen X, Zhang D (2013) Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen Res 8(21):2003–2014. https://doi.org/10.3969/j.issn.1673-5374.2013.21.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Halling JF, Pilegaard H (2017) Autophagy-dependent beneficial effects of exercise. Cold Spring Harbor Perspect Med 7(8):a029777. https://doi.org/10.1101/cshperspect.a029777

  44. Harrison D, Griendling KK, Landmesser U, Hornig B, Drexler H (2003) Role of oxidative stress in atherosclerosis. Am J Cardiol 91(3l):7–11. https://doi.org/10.1016/S0002-9149(02)03144-2

    Article  Google Scholar 

  45. He F, Li J, Liu Z, Chuang CC, Yang W, Zuo L (2016) Redox mechanism of reactive oxygen species in exercise. Front Physiol 7:486. https://doi.org/10.3389/fphys.2016.00486

  46. Higashi Y, Noma K, Yoshizumi M, Kihara Y (2009) Endothelial function and oxidative stress in cardiovascular diseases. Circ J 73(3):411–418. https://doi.org/10.1253/circj.cj-08-1102

    Article  CAS  PubMed  Google Scholar 

  47. Howden R (2013) Nrf2 and Cardiovascular Defense. Oxid Med Cell Longev 2013:104308. https://doi.org/10.1155/2013/104308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Huang Z, Wu M, Zeng L, Wang D (2022) The Beneficial Role of Nrf2 in the Endothelial Dysfunction of Atherosclerosis. Cardiol Res Pract 2022:4287711. https://doi.org/10.1155/2022/4287711

    Article  PubMed  PubMed Central  Google Scholar 

  49. Hyatt JPK (2022) MOTS-c increases in skeletal muscle following long-term physical activity and improves acute exercise performance after a single dose. Physiol Rep 10(13):e15377. https://doi.org/10.14814/phy2.15377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Jiang J, Dong C, Zhai L, Lou J, Jin J, Cheng S, Chen Z, Guo X, Lin D, Ding J, Gao W (2021) Paeoniflorin Suppresses TBHP-Induced Oxidative Stress and Apoptosis in Human Umbilical Vein Endothelial Cells via the Nrf2/HO-1 Signaling Pathway and Improves Skin Flap Survival. Front Pharmacol 12:735530. https://doi.org/10.3389/fphar.2021.735530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Jiang H, Zhou Y, Nabavi SM, Sahebkar A, Little PJ, Xu S, Weng J, Ge J (2022) Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis. Front Cardiovasc Med 9:925923. https://doi.org/10.3389/fcvm.2022.925923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Joffre J, Hellman J (2021) Oxidative Stress and Endothelial Dysfunction in Sepsis and Acute Inflammation. Antioxid Redox Signal 35(15):1291–1307. https://doi.org/10.1089/ars.2021.0027

    Article  CAS  PubMed  Google Scholar 

  53. Kadenbach B (2020) Regulation of cytochrome c oxidase contributes to health and optimal life. World J Biol Chem 11(2):52–61. https://doi.org/10.4331/wjbc.v11.i2.52

    Article  PubMed  PubMed Central  Google Scholar 

  54. Kim HW, Shi H, Winkler MA, Lee R, Weintraub NL (2020) Perivascular Adipose Tissue and Vascular Perturbation/Atherosclerosis. Arterioscler Thromb Vasc Biol 40(11):2569–2576. https://doi.org/10.1161/ATVBAHA.120.312470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kitaoka Y (2021) The Role of Nrf2 in Skeletal Muscle on Exercise Capacity. Antioxidants (Basel) 10(11):1712. https://doi.org/10.3390/antiox10111712

    Article  CAS  PubMed  Google Scholar 

  56. Kurutas EB (2016) The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr J 15:71. https://doi.org/10.1186/s12937-016-0186-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Laufs U, Wassmann S, Czech T, Münzel T, Eisenhauer M, Böhm M, Nickenig G (2005) Physical Inactivity Increases Oxidative Stress, Endothelial Dysfunction, and Atherosclerosis. Arter Throm Vasc Biol 25(4):809–814. https://doi.org/10.1161/01.ATV.0000158311.24443.af

    Article  CAS  Google Scholar 

  58. Laursen JB, Somers M, Kurz S, McCann L, Warnholtz A, Freeman BA, Tarpey M, Fukai T, Harrison DG (2001) Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin. Circulation 103(9):1282–1288. https://doi.org/10.1161/01.cir.103.9.1282

    Article  CAS  PubMed  Google Scholar 

  59. Laurson KR, Eisenmann JC, Welk GJ, Wickel EE, Gentile DA, Walsh DA (2008) Combined influence of physical activity and screen time recommendations on childhood overweight. J Pediatr 153(2):209–214. https://doi.org/10.1016/j.jpeds.2008.02.042

    Article  PubMed  Google Scholar 

  60. Lawler HM, Underkofler CM, Kern PA, Erickson C, Bredbeck B, Rasouli N (2016) Adipose Tissue Hypoxia, Inflammation, and Fibrosis in Obese Insulin-Sensitive and Obese Insulin-Resistant Subjects. J Clin Endocrinol Metab 101(4):1422–1428. https://doi.org/10.1210/jc.2015-4125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Lee J, Giordano S, Zhang J (2012) Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling. Biochem J 441(2):523–540. https://doi.org/10.1042/BJ20111451

    Article  CAS  PubMed  Google Scholar 

  62. Lemecha M, Morino K, Imamura T, Iwasaki H, Ohashi N, Ida S, Sato D, Sekine O, Ugi S, Maegawa H (2018) MiR-494-3p regulates mitochondrial biogenesis and thermogenesis through PGC1-α signalling in beige adipocytes. Sci Rep 8(1):1–14. https://doi.org/10.1038/s41598-018-33438-3

    Article  CAS  Google Scholar 

  63. Li H, Horke S, Förstermann U (2014) Vascular oxidative stress, nitric oxide and atherosclerosis. Atherosclerosis 237(1):208–219. https://doi.org/10.1016/j.atherosclerosis.2014.09.001

    Article  CAS  PubMed  Google Scholar 

  64. Li S, Laher I (2015) Exercise Pills: At the Starting Line. Trends Pharmacol Sci 36(12):906–917. https://doi.org/10.1016/j.tips.2015.08.014

    Article  CAS  PubMed  Google Scholar 

  65. Li S, Laher I (2017) Exercise Mimetics: Running Without a Road Map. Clin Pharmacol Ther 101(2):188–190. https://doi.org/10.1002/cpt.533

    Article  CAS  PubMed  Google Scholar 

  66. Li Y, Meng W, Hou Y, Li D, Wang X, Wu K, Sun S, Liu H, Li X, Lin F, Zhao G (2021) Dual Role of Mitophagy in Cardiovascular Diseases. J Cardiovasc Pharmacol 78(1):e30–e39. https://doi.org/10.1097/FJC.0000000000001046

    Article  CAS  PubMed  Google Scholar 

  67. Li S, Wang M, Ma J, Pang X, Yuan J, Pan Y, Fu Y, Laher I (2022) MOTS-c and Exercise Restore Cardiac Function by Activating of NRG1-ErbB Signaling in Diabetic Rats. Front Endocrinol 17(13):812032. https://doi.org/10.3389/fendo.2022.812032

    Article  Google Scholar 

  68. Liu Z, Khalil RA (2018) Evolving mechanisms of vascular smooth muscle contraction highlight key targets in vascular disease. Biochem Pharmacol 153:91–122. https://doi.org/10.1016/j.bcp.2018.02.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Ma Q (2013) Role of Nrf2 in Oxidative Stress and Toxicity. Annu Rev Pharmacol Toxicol 53:401–426. https://doi.org/10.1146/annurev-pharmtox-011112-140320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Mann S, Beedie C, Jimenez A (2014) Differential Effects of Aerobic Exercise, Resistance Training and Combined Exercise Modalities on Cholesterol and the Lipid Profile: Review. Synth Recomm Sports Med 44(2):211–221. https://doi.org/10.1007/s40279-013-0110-5

    Article  Google Scholar 

  71. Marcu R, Choi YJ, Xue J, Fortin CL, Wang Y, Nagao RJ, Xu J, MacDonald JW, Bammler TK, Murry CE, Muczynski K, Stevens KR, Himmelfarb J, Schwartz SM, Zheng Y (2018) Human organ-specific endothelial cell heterogeneity. IScience 4:20–35. https://doi.org/10.1016/j.isci.2018.05.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. De Matteis R, Lucertini F, Guescini M, Polidori E, Zeppa S, Stocchi V, Cinti S, Cuppini R (2013) Exercise as a new physiological stimulus for brown adipose tissue activity. Nutr Metab Cardiovasc Dis 23(6):582–590. https://doi.org/10.1016/j.numecd.2012.01.013

    Article  CAS  PubMed  Google Scholar 

  73. Miao CY, Li ZY (2012) The role of perivascular adipose tissue in vascular smooth muscle cell growth. Brit JPharmacol 165(3):643. https://doi.org/10.1111/j.1476-5381.2011.01404.x

    Article  CAS  Google Scholar 

  74. Mokdad AH, Marks JS, Stroup DF, Gerberding JL (2004) Actual causes of death in the United States, 2000. JAMA 291(10):1238–1245. https://doi.org/10.1001/jama.291.10.1238

    Article  PubMed  Google Scholar 

  75. Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417(Pt 1):1. https://doi.org/10.1042/BJ20081386

    Article  CAS  PubMed  Google Scholar 

  76. Ng SW, Popkin BM (2012) Time use and physical activity: a shift away from movement across the globe. Obes Rev 13(8):659–680. https://doi.org/10.1111/j.1467-789X.2011.00982.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Omar A, Chatterjee TK, Tang Y, Hui DY, Weintraub NL (2014) Proinflammatory phenotype of perivascular adipocytes. Arterioscler Thromb Vasc Biol 34(8):1631–1636. https://doi.org/10.1161/ATVBAHA.114.303030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Oral O (2021) Nitric oxide and its role in exercise physiology. J Sports Med Phys Fitness 61(9):1208–1211. https://doi.org/10.23736/S0022-4707.21.11640-8

    Article  PubMed  Google Scholar 

  79. Ostrom EL, Valencia AP, Marcinek DJ, Traustadóttir T (2021) High intensity muscle stimulation activates a systemic Nrf2-mediated redox stress response. Free Radic Biol Med 172:82–89. https://doi.org/10.1016/j.freeradbiomed.2021.05.039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Paffenbarger RS Jr, Blair SN, Lee IM (2001) A history of physical activity, cardiovascular health and longevity: the scientific contributions of Jeremy N Morris, DSc, DPH. FRCP Int J Epidemio 30(5):1184–1192. https://doi.org/10.1093/ije/30.5.1184

    Article  Google Scholar 

  81. Park JH, Moon JH, Kim HJ, Kong MH, Oh YH (2020) Sedentary Lifestyle: Overview of Updated Evidence of Potential Health Risks. Korean J Fam Med 41(6):365–373. https://doi.org/10.4082/kjfm.20.0165

    Article  PubMed  PubMed Central  Google Scholar 

  82. Perrone MA, Feola A, Pieri M, Donatucci B, Salimei C, Lombardo M, Perrone A, Parisi A (2021) The Effects of Reduced Physical Activity on the Lipid Profile in Patients with High Cardiovascular Risk during COVID-19 Lockdown. Int J Environ Res Public Health 18(16):8858. https://doi.org/10.3390/ijerph18168858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Pick E (2020) Cell-Free NADPH Oxidase Activation Assays: A Triumph of Reductionism. Methods Mol Biol 2087:325–411. https://doi.org/10.1007/978-1-0716-0154-9_23

    Article  PubMed  Google Scholar 

  84. Qin Q, Delrio S, Wan J, Jay Widmer R, Cohen P, Lerman LO, Lerman A (2018) Downregulation of circulating MOTS-c levels in patients with coronary endothelial dysfunction. Int J Cardiol 254:23–27. https://doi.org/10.1016/j.ijcard.2017.12.001

    Article  PubMed  Google Scholar 

  85. Ray PD, Huang BW, Tsuji Y (2012) Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 24(5):981–990. https://doi.org/10.1016/j.cellsig.2012.01.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Ringvold HC, Khalil RA (2017) Protein Kinase C as Regulator of Vascular Smooth Muscle Function and Potential Target in Vascular Disorders. Adv Pharmacol 78:203–301. https://doi.org/10.1016/bs.apha.2016.06.002

    Article  CAS  PubMed  Google Scholar 

  87. Ross R (1999) Atherosclerosis–an inflammatory disease. N Engl J Med 340(2):115–126. https://doi.org/10.1056/NEJM199901143400207

    Article  CAS  PubMed  Google Scholar 

  88. Sakurai T, Ogasawara J, Shirato K, Izawa T, Oh-Ishi S, Ishibashi Y (2017) Exercise Training Attenuates the Dysregulated Expression of Adipokines and Oxidative Stress in White Adipose Tissue. Oxid Med Cell Longev 2017:9410954. https://doi.org/10.1155/2017/9410954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Sánchez-Rodríguez MA, Zacarías-Flores M, Correa-Muñoz E, Arronte-Rosales A, Mendoza-Núñez VM (2021) Oxidative Stress Risk Is Increased with a Sedentary Lifestyle during Aging in Mexican Women. Oxid Med Cell Longev 2021:9971765. https://doi.org/10.1155/2021/9971765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Savoia C, D’Agostino M, Lauri F, Volpe M (2011) Angiotensin type 2 receptor in hypertensive cardiovascular disease. Curr Opin Nephrol Hypertens 20(2):125–132. https://doi.org/10.1097/MNH.0b013e3283437fcd

    Article  CAS  PubMed  Google Scholar 

  91. Sitia S, Tomasoni L, Atzeni F, Ambrosio G, Cordiano C, Catapano A, Tramontana S, Perticone F, Naccarato P, Camici P, Picano E, Cortigiani L, Bevilacqua M, Milazzo L, Cusi D, Barlassina C, Sarzi-Puttini P, Turiel M (2010) From endothelial dysfunction to atherosclerosis. Autoimmun Rev 9(12):830–834. https://doi.org/10.1016/j.autrev.2010.07.016

    Article  CAS  PubMed  Google Scholar 

  92. Steinberg D, Witztum JL (2002) Is the Oxidative Modification Hypothesis Relevant to Human Atherosclerosis? Circulation. https://doi.org/10.1161/01.CIR.0000014762.06201.06

    Article  PubMed  Google Scholar 

  93. Strom J, Xu B, Tian X, Chen QM (2016) Nrf2 protects mitochondrial decay by oxidative stress. Faseb J 30(1):66–80. https://doi.org/10.1096/fj.14-268904

    Article  CAS  PubMed  Google Scholar 

  94. Sukhovershin RA, Yepuri G, Ghebremariam YT (2015) Endothelium-Derived Nitric Oxide as an Antiatherogenic Mechanism: Implications for Therapy. Methodist Debakey Cardiovasc J 11(3):166–171. https://doi.org/10.14797/mdcj-11-3-166

    Article  PubMed  PubMed Central  Google Scholar 

  95. Tai SC, Robb GB, Marsden PA (2004) Endothelial Nitric Oxide Synthase. Arterioscler Thromb Vasc Biol 24(3):405–412. https://doi.org/10.1161/01.ATV.0000109171.50229.33

    Article  CAS  PubMed  Google Scholar 

  96. Thosar SS, Johnson BD, Johnston JD, Wallace JP (2012) Sitting and endothelial dysfunction: the role of shear stress. Med Sci Monit 18(12):RA173-80. https://doi.org/10.12659/msm.883589

    Article  PubMed  PubMed Central  Google Scholar 

  97. Tirichen H, Yaigoub H, Xu W, Wu C, Li R, Li Y (2021) Mitochondrial Reactive Oxygen Species and Their Contribution in Chronic Kidney Disease Progression Through Oxidative Stress. Front Physiol. 23(12):627837. https://doi.org/10.3389/fphys.2021.627837

    Article  Google Scholar 

  98. Tonelli C, Chio IIC, Tuveson DA (2018) Transcriptional Regulation by Nrf2. Antioxid Redox Signal 29(17):1727–1745. https://doi.org/10.1089/ars.2017.7342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Tonkonogi M, Fernström M, Walsh B, Ji LL, Rooyackers O, Hammarqvist F, Wernerman J, Sahlin K (2003) Reduced oxidative power but unchanged antioxidative capacity in skeletal muscle from aged humans. Pflugers Arch 446(2):261–269. https://doi.org/10.1007/s00424-003-1044-9

    Article  CAS  PubMed  Google Scholar 

  100. Touyz RM, Briones AM (2011) Reactive oxygen species and vascular biology: implications in human hypertension. Hypertens Res 34(1):5–14. https://doi.org/10.1038/hr.2010.201

    Article  CAS  PubMed  Google Scholar 

  101. Trayhurn P (2013) Hypoxia and adipose tissue function and dysfunction in obesity. Physiol Rev 93(1):1–21. https://doi.org/10.1152/physrev.00017.2012

    Article  CAS  PubMed  Google Scholar 

  102. Urbina-Varela R, Castillo N, Videla LA, del Campo A (2020) Impact of Mitophagy and Mitochondrial Unfolded Protein Response as New Adaptive Mechanisms Underlying Old Pathologies: Sarcopenia and Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 21(20):7704. https://doi.org/10.3390/ijms21207704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Vallance P, Chan N (2001) Endothelial function and nitric oxide: clinical relevance. Heart 85(3):342–350. https://doi.org/10.1136/heart.85.3.342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Wang X, Chen L, Wang T, Jiang X, Zhang H, Li P, Lv B, Gao X (2015) Ginsenoside Rg3 antagonizes adriamycin-induced cardiotoxicity by improving endothelial dysfunction from oxidative stress via upregulating the Nrf2-ARE pathway through the activation of akt. Phytomedicine 22(10):875–884. https://doi.org/10.1016/j.phymed.2015.06.010

    Article  CAS  PubMed  Google Scholar 

  105. Wei M, Gan L, Liu Z, Liu L, Chang JR, Yin DC, Cao HL, Su XL, Smith WW (2020) Mitochondrial-Derived Peptide MOTS-c Attenuates Vascular Calcification and Secondary Myocardial Remodeling via Adenosine Monophosphate-Activated Protein Kinase Signaling Pathway. Cardiorenal Med 10(1):42–50. https://doi.org/10.1159/000503224

    Article  CAS  PubMed  Google Scholar 

  106. Wen CP, Wai JPM, Tsai MK, Yang YC, Cheng TYD, Lee MC (2011) Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet 378(9798):1244–1253. https://doi.org/10.1016/S0140-6736(11)60749-6

    Article  PubMed  Google Scholar 

  107. Xu S, Ilyas I, Little PJ, Li H, Kamato D, Zheng X, Luo S, Li Z, Liu P, Han J, Harding IC, Ebong EE, Cameron SJ, Stewart AG, Weng J (2021) Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies. Pharmacol Rev 73(3):924–967. https://doi.org/10.1124/pharmrev.120.000096

    Article  CAS  PubMed  Google Scholar 

  108. Xu M, Qi Q, Men L, Wang S, Li M, Xiao M, Chen X, Wang S, Wang G, Jia H, Liu C (2020) Berberine protects Kawasaki disease-induced human coronary artery endothelial cells dysfunction by inhibiting of oxidative and endoplasmic reticulum stress. Vasc Pharmacol. 127:106660. https://doi.org/10.1016/j.vph.2020.106660

    Article  CAS  Google Scholar 

  109. Yan X, Shen Z, Yu D, Zhao C, Zou H, Ma B, Dong W, Chen W, Huang D, Yu Z (2022) Nrf2 contributes to the benefits of exercise interventions on age-related skeletal muscle disorder via regulating Drp1 stability and mitochondrial fission. Free Radic Biol Med 178:59–75. https://doi.org/10.1016/j.freeradbiomed.2021.11.030

    Article  CAS  PubMed  Google Scholar 

  110. Youn JY, Gao L, Cai H (2012) The p47phox- and NADPH oxidase organiser 1 (NOXO1)-dependent activation of NADPH oxidase 1 (NOX1) mediates endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction in a streptozotocin-induced murine model of diabetes. Diabetologia 55(7):2069–2079. https://doi.org/10.1007/s00125-012-2557-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Zang Y, Chen D, Zhou B, Chen A, Wang J, Gao X, Chen Q, Li Y, Kang Y, Zhu G (2019) FNDC5 inhibits foam cell formation and monocyte adhesion in vascular smooth muscle cells via suppressing NFκB-mediated NLRP3 upregulation. Vasc Pharmacol 121:106579. https://doi.org/10.1016/j.vph.2019.106579

    Article  CAS  Google Scholar 

  112. Zhai D, Ye Z, Jiang Y, Xu C, Ruan B, Yang Y, Lei X, Xiang A, Lu H, Zhu Z, Yan Z, Wei D, Li Q, Wang L, Lu Z (2017) MOTS-c peptide increases survival and decreases bacterial load in mice infected with MRSA. Mol Immunol 92:151–160. https://doi.org/10.1016/j.molimm.2017.10.017

    Article  CAS  PubMed  Google Scholar 

  113. Zhang C (2008) The role of inflammatory cytokines in endothelial dysfunction. Basic Res Cardiol 103(5):398. https://doi.org/10.1007/s00395-008-0733-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Zhang F, Wang C, Wang H, Lu M, Li Y, Feng H, Lin J, Yuan Z, Wang X (2013) Ox-LDL promotes migration and adhesion of bone marrow-derived mesenchymal stem cells via regulation of MCP-1 expression. Mediators Inflamm 2013:691023. https://doi.org/10.1155/2013/691023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Zou MH, Shi C, Cohen RA (2002) Oxidation of the zinc-thiolate complex and uncoupling of endothelial nitric oxide synthase by peroxynitrite. J Clin Invest 109(6):817–826. https://doi.org/10.1172/JCI14442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

National Natural Science Foundation of China, grant number 31971104.

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Authors and Affiliations

  1. Faculty of Basic Clinical Sciences, Department of Pharmacology and Therapeutics, Bowen University, Iwo, Nigeria

    Babatunde Fasipe

  2. Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu, 610041, China

    Shunchang Li

  3. Faculty of Medicine, Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, Vancouver, Canada

    Ismail Laher

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Fasipe, B., Li, S. & Laher, I. Exercise and vascular function in sedentary lifestyles in humans. Pflugers Arch - Eur J Physiol 475, 845–856 (2023). https://doi.org/10.1007/s00424-023-02828-6

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