Cellular mechanisms of captopril-induced matrix remodeling in Syrian hamster cardiomyopathy.
Cellular mechanisms of captopril-induced matrix remodeling in Syrian hamster cardiomyopathy.
复制标题
卡托普利诱导叙利亚仓鼠心肌病基质重塑的细胞机制。
DOI：
10.1161/01.cir.90.3.1334
复制
发表时间：
1994
期刊：
影响因子：
37.8
通讯作者：
Wickline,SA
中科院分区：
文献类型：
--
作者：
Davison,G;Hall,CS;Miller,JG;Scott,M;Wickline,SA
背景虽然血管紧张素转换酶（ACE）抑制剂已成为治疗慢性充血性心力衰竭（CHF）的主要药物，但尚不清楚心脏重塑效应是否是由ACE抑制剂降低后负荷的血流动力学作用引起的继发现象，方法和实验我们使用超声组织定征来确定ACE治疗的潜在有益效果抑制剂对心脏的材料特性及其在细胞水平上对心脏重塑的潜在影响。10只1月龄的心肌病（CM）叙利亚仓鼠和6只正常（NL）仓鼠用卡托普利（2 g/L水，自由饮用）治疗，10只CM仓鼠和10只NL仓鼠保持未治疗3个月。心脏被切除，背散射射频数据从1200个独立的网站从每个标本与高分辨率50 MHz的声学显微镜计算积分背散射（IB）。在CM心脏中，卡托普利治疗可降低左心室质量、钙浓度和IB，而不影响肌纤维大小或胶原蛋白浓度。NL仓鼠、处理的CM仓鼠和未处理的CM仓鼠中心肌的大体正常区域的IB没有显著差异。IB从显微镜区域的疤痕组织在治疗的CM仓鼠显着低于（P = .0004），从疤痕组织在未处理的CM hamsters. CONCLUSIONSSThe减少IB从治疗的疤痕组织成分反映了具体的改变材料特性（弹性刚度，密度）的纤维区域在CM心脏诱导的卡托普利。这是第一份报告，定义了ACE抑制剂对实验性心肌病心脏组织分离组分材料特性的特定细胞效应。瘢痕组织成分的材料性质的这些改变代表了ACE抑制剂在心力衰竭中有益作用的潜在机制。
BACKGROUNDAlthough angiotensin-converting enzyme (ACE) inhibitors have become a mainstay of treatment for chronic congestive heart failure (CHF), it is not known whether the cardiac remodeling effects are a secondary phenomenon, resulting from ACE inhibitors' hemodynamic actions of afterload reduction, or occur through an independent mechanism.METHODS AND RESULTSWe used ultrasonic tissue characterization to define potentially salutary effects of treatment with ACE inhibitors on the material properties of the heart and its potential influence on cardiac remodeling at the cellular level. Ten 1-month-old, cardiomyopathic (CM) Syrian hamsters and 6 normal (NL) hamsters were treated with captopril (2 g/L water ad libitum), and 10 CM hamsters and 10 NL hamsters were maintained untreated for 3 months. Hearts were excised, and backscattered radiofrequency data were acquired from 1200 independent sites from each specimen with a high-resolution 50-MHz acoustic microscope for calculation of integrated backscatter (IB). Treatment with captopril reduced left ventricular mass, calcium concentration, and IB in CM hearts without affecting myofiber size or collagen concentration. The IB from grossly normal regions of myocardium in NL hamsters, treated CM hamsters, and untreated CM hamsters was not significantly different. The IB from the microscopic regions of scar tissue in treated CM hamsters was significantly less (P = .0004) than that from scar tissue in untreated CM hamsters.CONCLUSIONSThe reduced IB from treated scar tissue components reflects specific alterations in the material properties (elastic stiffness, density) of fibrous regions in CM hearts induced by captopril. This is the first report that defines specific cellular effects of ACE inhibitors on the material properties of isolated components of cardiac tissue in experimental cardiomyopathy. These alterations in material properties of scar tissue components represent a potential mechanism for the salutary actions of ACE inhibitors in heart failure.