Pulmonary vascular endothelial injury and pulmonary hypertension

Abstract

Abstract: Pulmonary arterial hypertension (PAH) is a group of clinical syndrome characterized by increasing pulmonary vascular resistance due to different etiologies and pathogenesis. Potential causes are not clear. More and more studies have shown that pulmonary vascular endothelial injury is the primary factor causing the characteristic pathological changes. In the different periods of PAH, protection of the pulmonary vascular endothelial cells and improvement of endothelial function or restoration of the balance between endogenous vasoactive substances, recovery of vascular endothelial integrity in terms of structure and function, and delay or reversal of the pulmonary vascular proliferation and remodeling processes, have become important goals for treatment of PAH.

Key words: Pulmonary vascular endothelial injury, Pulmonary hypertension, Treatment of pulmonary hypertension

CLC Number:

WU Cai-xia, DU Guan-hua. Pulmonary vascular endothelial injury and pulmonary hypertension[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(4): 463-471.

References

[1] Grimminger F, Schermuly RT. PDGF receptor and its antagonists: role in treatment of PAH[J]. Adv Exp Med Biol, 2010,661(6):435-446.
[2] Badesch DB,Champion HC,Gomez Sanchez MA,et a1.Diagnosis and assessment of pulmonary arterial hypertension[J].J Am Coil Cardiol,2009,54(1 Suppl):55-66.
[3] 程显声.特发性肺动脉高压的诊断[J].中国循环杂志,2006,21(6):478-480.
[4] 王新, 杨玉雯,王安才,等. 缬沙坦干预对缺氧性肺动脉高压大鼠大电导钙激活钾通道的影响[J]. 中国临床药理学与治疗学,2009,14(9):1032- 1035.
[5] Jurasz P, Courtman D, Babaie S, et al. Role of apoptosis in pulmonary hypertension: From experimental models to clinical trials[J]. Pharmacol Ther,2010,126(1):1-8.
[6] Budhiraja R, Tuder RM, Hassoun PM. Endothelial dysfunction in pulmonary hypertension[J].Circulation,2004,109(2):159-165.
[7] Rabinovitch M, Bothwell T, Hayakawa BN, et al. Pulmonary artery endothelial abnormalities in patients with congenital heart defects and pulmonary hypertension. A correlation of light with scanning electron microscopy and transmission electron microscopy[J]. Lab Invest,1986,55(6):632-653.
[8] 陈小容,邹霞英. 缺氧性肺动脉高压大鼠肺血管内皮细胞的变化[J]. 中国病理生理杂志,1996,12(6):608-611.
[9] 师桃,耿希刚.先天性心脏病肺动脉高压患者肺组织内皮型一氧化氮合成酶的表达及肺血管重建[J].西安交通大学学报:医学版,2003,24(1):37-39.
[10] 杨汉文,诸葛毅,王小同.激肽原酶对低氧二氧化碳模型大鼠肺动脉高压的影响[J].医药导报,2010, 29(8):989-993.
[11] Kong LL, Yan LD, Gong ZH. Endothelins system and myocardial hypertrophy[J]. Chin Pharm acol Bull, 2008, 24 (9) : 1127 - 1130.
[12] Langleben D. Endothelin receptor antagonists in the treatment of pulmonary arterial hypertension[J]. Clin Chest Med, 2007, 28 (1) :117 - 125.
[13] Marcos E,Adnot S,Pham MH,et al.Serotonin transporter inhibitors protectagainst hypoxic pulmonary hypertension[J].Am J Respir Crit Care Med,2003,168(3):487-493.
[14] Shi XD, Li ZL, Wu HC,et al. Effect of urotensin Ⅱ on secretion of adrenomedullin from human vascular endothelial cells[J]. Chin J Cardiol,2005,33 (9): 836-839.
[15] 赵翠芬, 王丽娟, 王志宇,等.肾上腺髓质素前体不同活性肽段在肺动脉高压大鼠肺内的变化[J].中国病理生理杂志,2008,24(4) : 655-660.
[16] 陈新军,刘亚萍,温绍君,等. 肾上腺髓质素与肺动脉高压[J]. 中华胸心血管外科杂志,2005, 21(6):381-382.
[17] 贾晓民,赵杰,王海清. 碱性成纤维细胞生长因子对肺癌A459细胞pim-3表达影响的实验研究 [J].南京医科大学学报:自然科学版,2009,29(6):845-847.
[18] Izikki M, Guignabert C, Fadel E, et al. Endothelial-derived FGF2 contributes to the progression of pulmonary hypertension in humans and rodents [J]. Clin Invest, 2009, 119(3):512-523.
[19] Tu L, Dewachter L, Gore B, et al. Autocrine FGF2 signaling contributes to altered endothelial phenotype in pulmonary hypertension [J]. Am J Respir Cell Mol Biol, 2011,45(2):311-322.
[20] Perros F, Montani D, Dorfmuller P, et al. Platelet-derived growth factor expression and function in idiopathic pulmonary arterial hypertension [J]. Am J Respir Crit Care Med,2008,178(1):81-88.
[21] Schermuly RT, Dony E, Ghofrani HA, et al. Reversal of experimental pulmonary hypertension by PDGF inhibition[J].J Clin Invest,2005,115(10): 2811-2821.
[22] Ghofrani HA, Seeger W, Grimminger F. Imatinib for the treatment of pulmonary arterial hypertension[J]. N Engl J Med,2005,353(13): 1412-1413.
[23] Patterson KC, Weissmann A, Ahmadi T,et al. Imatinib mesylate in the treatment of refractory idiopathic pulmonary arterial hypertension[J]. Ann Intern Med,2006,145(2):152-153.
[24] Souza R, Sitbon O, Parent F, et al. Long term imatinib treatment in pulmonary arterial hypertension[J]. Thorax, 2006,61(8):736.
[25] 熊迈,姚尖平,徐颖琦,等. 两种大鼠肺动脉高压模型转化生长因子-β₁及其I型受体表达的比较[J]. 中华实验外科杂志,2009,26(6):767-769.
[26] Long L,Crosby A,Yang X,et al.Altered bone morphogenetic protein and transforming growth factor-beta signaling in rat models of pulmonary hypertension:potential for activin receptor-like kinase-5 inhibition in prevention and progression of disease[J].Circulation, 2001,103(5):779.
[27] Yoshida H, Kitaichi T, Urata M, et al. Syngeneic bone marrow mononuclear cells improve pulmonary arterial hypertension through vascular endothelial growth factor upregulation[J]. Ann Thorac Surg, 2009,88(2):418-424.
[28] Sakamaki F, Kyotani S, Nagaya N, et al. Increased plasma P-selectin and decreased thrombomodulin in pulmonary arterial hypertension were improved by continuous prostacyclin therapy [J].Circulation, 2001,103(5):779.
[29] Kawut SM, Horn EM, Berekashvili KK, et al. von Willebrand factor independently predicts long-term survival in patients with pulmonary arterial hypertension[J]. Chest, 2005, 128(4):2355-2362.
[30] Rabinovitch M. Molecularpathogenesis of pulmonary arterial hypertension[J]. J Clin Invest, 2008, 118(7): 2372-2379.
[31] Sakao S,Taraseviciene-Stewart L, Lee JD, et al. Initial apoptosis is followed by increased proliferation of apoptosis-resistant endothelial cells[J]. FASEB J, 2005, 19 (9): 1178-1180.
[32] Jurasz P, Courtman D, Babaie S, et al. Role of apoptosis in pulmonary hypertension: from experimental models to clinical trials [J]. Pharmacol Ther,2010,126(1):1-8.
[33] LévyM, Maurey C, Celermajer DS, et al. Impaired apoptosis of pulmonary endothelial cells is associated with intimal proliferation and irreversibility of pulmonary hypertension in congenital heart disease[J]. J Am Coll Cardiol, 2007, 49 (7) :803-810.
[34] Masri FA, Xu W, Comhair SA, et al. Hyperproliferative apoptosis-resistant endothelial cells in idiopathic pulmonary arterial hypertension1 [J]. Am J Physiol Lung Cell Mol Physiol, 2007,293(3):L548-554.
[35] 左祥荣,解卫平,王虹. 内皮细胞凋亡与肺动脉高压[J]. 国际内科学杂志,2009, 36(8):487-490.
[36] Ibe BO,Abdallah MF,Portugal AM.Platelet-activating factor stimulates ovine foetal pulmonary vascular smooth muscle cell proliferation:role of nuclear factor-kappa B and cyclin-dependent kinases[J].Cell Prolif,2008,41(2):208-229.
[37] Bixby CE,Ibe BO,Abdallah MF,et al. Role of platelet - activating factor in pulmonary vascular remodeling associated with chronic high altitude hypoxia in ovine fetal lambs[J].Am J Physiol Lung Cell Mol Physio1,2007,293(6):L1475-L1482.
[38] Humbert M, Sitbon O, Chaouat A, et al. Survival in patients with idiopathic, familial, and anorexigenassociated pulmonary arterial hypertension in the modern management era[J]. Circulation,2010,122(2):156-163.
[39] 肖雄, 侯颖, 李小强. 5-羟色胺受体拮抗剂在肺动脉高压防治中的应用与展望[J].中国临床药理学与治疗学,2011,16(1):111-115.
[40] Vachiéry JL. Prostacyclins in pulmonary arterial hypertension: the need for earlier therapy[J]. Adv Ther, 2011,28(4):251-269.
[41] 许蜀闽,郑绿珍,刘福玉. L-精氨酸和牛磺酸联合抗缺氧损伤及防治缺氧性肺动脉高压的研究[J].局解手术学杂志,2006,15(4):217-219.
[42] Badesch DB, Abman SH, Simonneau G, et al.Medical therapy for pulmonary arterial hypertension: updated ACCP evidence base clinicaI practice guidelines[J].Chest,2007,131(6):1917-1928.
[43] Chin KM,Rubin U.Pulmonary artlrial hypertension [J].J Am Coll Cardiol,2008,51(16):1527-1538.
[44] Montani D, Chaumais MC, Savale L,et al. Phosphodiesterase type 5 inhibitors in pulmonary arterial hypertension[J]. Adv Ther, 2009, 26(9):813-825.
[45] Xiong CM, He JG, Lu XL, et al. Preliminary study on the efficacy and safety of oral sildenafil in pulmonary arterial hypertension in China [J]. Zhonghua Yi Xue Za Zhi,2011,91(6):370-374.
[46] Levin YD, White RJ. Novel therapeutic approaches in pulmonary arterial hypertension: focus on tadalafil[J]. Drugs Today (Barc), 2011, 47(2):145-156.
[47] Fukumoto Y, Shimokawa H. The role of Rho-kinase pathway on PAH [J]. Nippon Rinsho, 2008, 66(11): 2091-2096.
[48] 张锐, 刘岽, 袁平,等. Rho激酶抑制剂治疗肺动脉高压的研究进展 [J].中华医学杂志, 2010, 90(26):1869-1871.
[49] 孟刘坤, 刘成硅. 内皮祖细胞在肺动脉高压治疗中的应用[J]. 岭南心血管病杂志,2009,15(2):155-157.
[50] Zhang F,Wu S,Lu X,et al.Gene transfer of endothelial nitric oxide synthase attenuates flow-induced pulmonary hypertension in rabbits [J].Ann Thorac Surg,2008,85(2):58l-585.