Secretion and effects of angiotensin-converting enzyme 2 on pulmonary vascular remodeling in pulmonary embolism rats
DENG Yicai1 HUANG Mingchao1 CHEN Li2 YE Yongquan3 YOU Jinhui1 SU Biaokun1 CHEN Zhuo4 DONG Fang1.2
1.Department of Respiration Medicine, Fuzhou Second Hospital Affiliated to Xiamen University, Fujian Province, Fuzhou 350007, China;
2.Office of Fuzhou Economic and Technological Development Zone Hospital, Fujian Province, Fuzhou 350107, China;
3.Department of Pathology, Fuzhou Second Hospital Affiliated to Xiamen University, Fujian Province, Fuzhou 350007, China;
4.Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fujian Province, Fuzhou 350002, China
Abstract：Objective To measure angiotensin-converting enzyme 2 (ACE2) concentrations in peripheral blood and pulmonary artery trunk at different time points during the pulmonary embolism in rats, in order to investigate the effects of ACE2 on pulmonary vascular remodeling. Methods 120 male rats were randomly divided into pulmonary embolism group, control group and sham surgury group by random number table, with 40 rats in each group. Then, according to the different time points after embolization, the rats in pulmonary embolism group were further divided into 5 subgroups: embolization 24 h group, embolization 1 week group, embolization 2 weeks group, embolization 4 weeks group and embolization 8 weeks group. Concentrations of ACE2 both in pulmonary artery trunk and peripheral blood were measured at the corresponding time point, as well as the pathological examinations of pulmonary artery trunks. Results Compared with control group, the concentrations of ACE2 in the pulmonary trunk and peripheral blood of the sham operation group were not statistically significant (P > 0.05). While the concentrations of ACE2 in pulmonary embolism group were significantly lower than those in control group at 1 week, 2 weeks, 4 weeks and 8 weeks after embolization (P < 0.01). Meanwhile, pathological examination results showed clearly the infiltration of inflammatory cells around pulmonary artery trunk, pulmonary fibrosis and vascular remodeling with a hyperplasia of granulation tissue. Conclusion The expression of ACE2 reduced significantly in pulmonary embolism rat model, and the low concentrations of ACE2 may aggravate pulmonary vascular remodeling.
[1] 中华医学会心血管病学分会肺血管病学组，中国医师协会心血管内科医师分会.急性肺栓塞栓塞症诊断治疗中国专家共识[J].中华内科杂志，2010，49（1）：74-81.
[2] Goldhaber SZ. Venous thromboembolism：epidemiology and magnitude of the problem [J]. Best Pract Res Clin Haematol，2012，25（3）：235-242.
[3] 程显声.进一步提高肺动脉栓寒诊断与处理水平[J].中华结核和呼吸杂志，2000，23（9）：517-518.
[4] 张敬霞，陈永利，王佩显，等.实验性急性肺血栓栓塞症肺动脉血管重构及意义[J].天津医药，2007，35（6）：423-433.
[5] Jaff MR，McMurtry MS，Archer SL，et al. Management of massive and submassive pulmonary embolism， iliofemoral deep vein thrombosis， and chronic thromboembolic pulmonary hypertension：a scientific statement from the American Heart Association [J]. Circulation，2011，123（16）：1788-1830.
[6] 刘春萍，张运剑，陆慰萱，等.急性肺栓塞大鼠肺表面活性物质的变化[J].中华结核和呼吸杂志，2005，28（9）：600-603.
[7] Bresalier RS，Ho SB，Schoeppner HL，et a1. Enhanced sialylation of mucin-associated carbohydrate structures in human colon cancer metastasi[J].Gastroenterolgy，1996， 110（5）：1354-1367.
[8] Orte C，Polak JM，Haworth SG，et al. Expression of pulmonary vascular angiotensin-converting enzyme in primary and secondary plexiform pulmonary hypertension [J]. J Pathol，2000，192（3）：379-384.
[9] Zhu Z，Ma B，Zheng T，et al. IL-13-induced chemokine responses in the lung：role of CCR2 in the pathogenesis of IL-13-induced inflammation and remodeling [J]. J Immunol，2002，168（6）：2953-2962.
[10] Mehta PK，Griendling KK. Angiotensin Ⅱ cell signaling：physiological and pathological effects in the cardiovascular system [J]. Am J Physiol Cell Physiol，2007，292（1）：C82－C97.
[11] 文海若，李波，付研.血管紧张素Ⅱ在心血管疾病中的氧化应激调节机制[J].中国医刊，2014，49（2）：12-14.
[12] Montezano AC，Nguyen Dinh Cat A，Rios FJ，et al. Angiotensin Ⅱand vascular injury [J]. Curr Hypertens Rep，2014，16（6）：1-11.
[13] Donoghue M，Hsieh F，Baronas E，et al. A novel angiotensin-converting enzyme-related carboxypeptidase （ACE2） converts angiotensin I to angiotensin 1-9 [J]. Circ Res，2000， 87（5）：E1-E9.
[14] Tipnis SR，Hooper NM，Hyde R，et al.A human homolog of angiotensin-converting enzyme.Cloning and functional expression as a captopril-insensitive carboxypeptidase [J]. J Biol Chem，2000，275（43）：33 238-33 243.
[15] Boehm M，Nabel EG.Angiotens-inconverting enzyme 2-a new cardiac regulator [J]. N Engl J Med，2002，347（22）：1795-1797.
[16] Osei SY，Ahima RS，Minkes RK，et al.Differential responses to angiotensin-（1-7） in the feline mesenteric and hindquarters vascular beds [J]. Eur J Pharmacol，1993，234（1）：35-42.
[17] Ferrario CM. Angiotensin-（1-7） and antihypertention mechanisms [J]. Nephrol，1998，11（6）：278-283.
[18] Bernstein KE，Ong FS，Blackwell WL，et al. A modern understanding of the traditional and nontraditional biological functions of angiotensin-converting enzyme [J]. Pharmacol Rev，2013，65（1）：544.
[19] Chen LN，Yang XH，Nissen DH，et al. Dysregulated rennin-angiotensin system contributes to acute lung injury caused by hind-limb ischemia-reperfusion in mice [J]. Shock，2013，40（5）：420-429.
[20] Patel VB，Zhong JC，Fan D，et al. Angiotensin converting-enzyme 2 is a critical determinant of angiotensin Ⅱ-induced loss of vascular smooth muscle cells and adverse vascular remodeling [J]. Hypertension，2014，64（1）：157-164.
[21] Nie W，Yan H，Li S，et al. Angiotensin-（1-7） enhances angiotensin Ⅱ induced phosphorylation of ERK1/2 in mouse bonemarrow-derived dendritic cells [J]. Mol Immunol，2009，46：355-361.
[22] Ferrario CM，Varagic J. The ANG-（1-7）/ACE2/mas axis in the regulation of nephron function [J]. Am J Physiol Renal Physiol，2010，298（6）：F1297-F1305.
2017, Vol. 14 
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