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Expression of tissue factor and forkhead box transcription factor O-1 in a rat model for chronic thromboembolic pulmonary hypertension

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Abstract

Few reports have examined tissue factor (TF) and forkhead box transcription factor O-1 (FoxO1) expression in chronic thromboembolic pulmonary hypertension (CTEPH) animal models. To investigate the role of TF and FoxO1 and their interactions during CTEPH pathogenesis in a rat model. Autologous blood clots were repeatedly injected into the pulmonary arteries through right jugular vein to induce a rat model of CTEPH. Hemodynamic parameters, histopathology, and TF and FoxO1expression levels were detected. The mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance and vessel wall area/total area (WA/TA) ratio in the experiment group increased significantly than sham group (P < 0.05). The cardiac output in the 1-, 2-, and 4-week groups decreased significantly (P < 0.05) when compared to sham group. TF mRNA expression levels in the experiment group increased significantly than sham group (P < 0.05). FoxO1 mRNA and protein expression levels were lower in the experiment group than sham group (P < 0.05). The mPAP had a positive correlation with WA/TA ratio (r = 0.45, P = 0.01). TF mRNA expression had a positive correlation with WA/TA ratio (r = 0.374, P = 0.035) and a positive correlation with mPAP (r = 0.48, P= 0.005). FoxO1 mRNA expression had a negative correlation trend with the WA/TA ratio (r = −0.297, P = 0.099) and a negative correlation trend with mPAP (r = −0.34, P = 0.057). TF mRNA expression had a negative correlation with FoxO1 mRNA expression (r = −0.62, P < 0.001). A rat model of CTEPH can be successfully established by the injection of autologous blood clots into the pulmonary artery. TF and FoxO1 may play a key role in vascular remodeling during CTEPH pathogenesis.

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References

  1. Hoeper MM (2014) Chronic thromboembolic pulmonary hypertension at the crossroad. Eur Respir J 5:1230–1232

    Article  Google Scholar 

  2. Toshner M, Pepke-Zaba J (2014) Chronic thromboembolic pulmonary hypertension: time for research in pathophysiology to catch up with developments in treatment. F1000Prime Rep 6: 38

  3. Riedel M, Stanek V, Widimsky J, Prerovsky I (1982) Longterm follow-up of patients with pulmonary thromboembolism. Late prognosis and evolution of hemodynamic and respiratory data. Chest 2:151–158

    Article  Google Scholar 

  4. Diaz JA, Obi AT, Myers DD Jr et al (2012) Critical review of mouse models of venous thrombosis. Arterioscler Thromb Vasc Biol 3:556–562

    Article  Google Scholar 

  5. Vaidyula VR, Criner GJ, Grabianowski C, Rao AK (2009) Circulating tissue factor procoagulant activity is elevated in stable moderate to severe chronic obstructive pulmonary disease. Thromb Res 3:259–261

    Article  Google Scholar 

  6. Bokarewa MI, Morrissey JH, Tarkowski A (2002) Tissue factor as a proinflammatory agent. Arthritis Res 3:190–195

    Article  Google Scholar 

  7. Zhang JX, Chen YL, Zhou YL, Guo QY, Wang XP (2014) Expression of tissue factor in rabbit pulmonary artery in an acute pulmonary embolism model. World J Emerg Med 2:144–147

    Article  Google Scholar 

  8. Accili D, Arden KC (2004) FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell 117:421–426

    Article  CAS  PubMed  Google Scholar 

  9. Wang Y, Zhou Y, Graves DT (2014) FOXO Transcription factors: their clinical significance and regulation. Biomed Res Int 2014:925350

    PubMed  PubMed Central  Google Scholar 

  10. Savai R, Al-Tamari HM, Sedding D et al (2014) Pro-proliferative and inflammatory signaling converge on FoxO1 transcription factor in pulmonary hypertension. Nat Med 20:1289–1300

    Article  CAS  PubMed  Google Scholar 

  11. Eskelinen EL, Saftig P (2009) Autophagy: a lysosomal degradation pathway with a central role in health and disease. Biochim Biophys Acta 1793:664–673

    Article  CAS  PubMed  Google Scholar 

  12. Grandi L, Grandi RA, Tomasi CD, da Rocha JL, Cardoso V, Dal-Pizzol F (2013) Acute and chronic consequences of polidocanol foam injection in the lung in experimental animals. Phlebology 8:441–444

    Article  Google Scholar 

  13. Sato H, Hall CM, Griffith GW et al (2008) Large animal model of chronic pulmonary hypertension. ASAIO J 4:396–400

    Article  Google Scholar 

  14. Hori Y, Uchide T, Saitoh R et al (2012) Diagnostic utility of NT-proBNP and ANP in a canine model of chronic embolic pulmonary hypertension. Vet J 2:215–221

    Article  Google Scholar 

  15. Ji YQ, Feng M, Zhang ZH, Lu WX, Wang C (2013) Varied response of the pulmonary arterial endothelium in a novel rat model of venous thromboembolism. Chin Med J 1:114–117

    Google Scholar 

  16. Deng C, Wu D, Zhai Z et al (2015) Close concordance between pulmonary angiography and pathology in a canine model with chronic pulmonary thromboembolism and pathological mechanisms after lung ischemia reperfusion injury. J Thromb Thrombolysis 41(4):581–591

    Article  PubMed Central  Google Scholar 

  17. Virchow R (1846) Thrombosis and emboli. Science History, Canton

    Google Scholar 

  18. Runyon MS, Gellar MA, Sanapareddy N, Kline JA, Watts JA (2010) Development and comparison of a minimally-invasive model of autologous clot pulmonary embolism in Sprague–Dawley and Copenhagen rats. Thrombosis J 8:3

    Article  Google Scholar 

  19. Deng CS, Yang MX, Lin QC et al (2014) Beneficial effects of inhaled NO on apoptotic pneumocytes in pulmonary thromboembolism model. Theor Biol Med Model 11:36

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kamikura Y, Wada H, Nobori T et al (2005) Elevated levels of leukocyte tissue factor mRNA in patients with venous thromboembolism. Thromb Res 4:307–312

    Article  Google Scholar 

  21. Darbousset R, Thomas GM, Mezouar S et al (2012) Tissue factor-positive neutrophils bind to injured endothelial wall and initiate thrombus formation. Blood 120:2133–2143

    Article  CAS  PubMed  Google Scholar 

  22. Tormoen GW, Rugonyi S, Gruber A, McCarty OJ (2011) The role of carrier number on the procoagulant activity of tissue factor in blood and plasma. Phys Biol 8:066005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Garcia Rodriguez P, Eikenboom HC, Tesselaar ME et al (2010) Plasma levels of microparticle-associated tissue factor activity in patients with clinically suspected pulmonary embolism. Thromb Res 4:345–349

    Article  Google Scholar 

  24. Vieira LM, Dusse LM, Fernandes AP (2007) Monocytes and plasma tissue factor levels in normal individuals and patients with deep venous thrombosis of the lower limbs: potential diagnostic tools? Thromb Res 2:157–165

    Article  Google Scholar 

  25. Zhou J, May L, Liao P, Liao P, Gross PL, Weitz JI (2009) Inferior vena cava ligation rapidly induces tissue factor expression and venous thrombosis in rats. Arterioscler Thromb Vasc Biol 29:863–869

    Article  CAS  PubMed  Google Scholar 

  26. White TA, Witt TA, Pan S et al (2010) Tissue factor pathway inhibitor overexpression inhibits hypoxia-induced pulmonary hypertension. Am J Respir Cell Mol Biol 1:35–45

    Article  Google Scholar 

  27. Emilie R, Malgorzata M, Olivier B (2013) Endothelial FoxO1 is an intrinsic regulator of thrombospondin-1 expression that restrains angiogenesis in ischemic muscle. Angiogenesis 16:759–772

    Article  Google Scholar 

  28. Milkiewicz M, Roudier E, Doyle JL et al (2011) Identification of a mechanism underlying regulation of the anti-angiogenic forkhead transcription factor FoxO1 in cultured endothelial cells and ischemic muscle. Am J Pathol 178:935–944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hsu CP, Zhai P, Yamamoto T et al (2010) Silent information regulator1 protects the heart from ischemia/reperfusion. Circulation 21:2170–2182

    Article  Google Scholar 

  30. Liu J, Tang Y, Feng Z et al (2014) Acetylated FoxO1 mediates high-glucose induced autophagy in H9c2 cardiomyoblasts: regulation by apolyphenol-(−)-epigallocatechin-3-gallate. Metabolism 10:1314–1323

    Article  Google Scholar 

  31. Mortuza R, Chen S, Feng B, Sen S, Chakrabarti S (2013) High glucose induced alteration of SIRTs in endothelial cells causes rapid aging in a p300 and FOXO regulated pathway. PLoS One 8:e54514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ryter SW, Lee SJ, Smith A, Choi AM (2010) Autophagy in vascular disease. Proc Am Thorac Soc 7:40–47

    Article  PubMed  PubMed Central  Google Scholar 

  33. Zhang X, Jin Y, Xia L, Tao X, Bai M, Zhang J (2009) Hsp90 mediates the balance of nitric oxide and superoxide anion in the lungs of rats with acute pulmonary thromboembolism. Int Immunopharmacol 1:43–48

    Article  Google Scholar 

Download references

Funding

This study was supported by National Natural Science Foundation of China (81570264), and Fujian Provincial Medical Innovation Subject (2014-CXB-12).

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    Authors and Affiliations

    1. Division of Respiratory and Critical Care Medicine, First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China

      Chaosheng Deng, Dawen Wu, Minxia Yang, Yunfei Chen, Caiyun Wang, Zhanghua Zhong, Ningfang Lian, Hua Chen & Shuang Wu

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    1. Chaosheng Deng
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    2. Dawen Wu
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    Correspondence to Chaosheng Deng.

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    Chaosheng Deng and Dawen Wu have contributed equally to this work.

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    Deng, C., Wu, D., Yang, M. et al. Expression of tissue factor and forkhead box transcription factor O-1 in a rat model for chronic thromboembolic pulmonary hypertension. J Thromb Thrombolysis 42, 520–528 (2016). https://doi.org/10.1007/s11239-016-1413-9

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