COLLAGEN REMODELING OF THE PRESSURE-OVERLOADED, HYPERTROPHIED NONHUMAN PRIMATE MYOCARDIUM
COLLAGEN REMODELING OF THE PRESSURE-OVERLOADED, HYPERTROPHIED NONHUMAN PRIMATE MYOCARDIUM
复制标题
DOI：
10.1161/01.res.62.4.757
复制
发表时间：
1988-04-01
影响因子：
20.1
通讯作者：
BASHEY, RI
中科院分区：
文献类型：
--
作者：
WEBER, KT;JANICKI, JS;BASHEY, RI
心肌系在纤维性胶原蛋白基质中，以最大限度地产生力量。在人类压力超载、肥厚的左心室中，胶原蛋白浓度已知升高，但胶原蛋白的结构和生化重塑及其与细胞坏死和心肌力学的关系尚不清楚。因此，本研究在由逐渐发生的实验性高血压引起的左心室肥厚的非人灵长类动物模型中进行。测定胶原蛋白的数量、光镜特征以及I、III、V型胶原蛋白的比例，同时测定完整心室在V期的舒张和收缩力学，以及在左心室肥厚的进化、早期和晚期（分别为4、35和88周）完整心室的舒张和收缩力学。与对照组相比，我们发现1)在没有心肌细胞坏死的情况下，第4周胶原蛋白增加，III型比例更大；2) 35周时胶原隔变厚、致密，ⅰ型和ⅲ型比例转为对照；3) 88周坏死明显，结构重塑及ⅰ型、ⅲ型胶原比例反映瘢痕形成程度；4)与舒张心肌硬度不同，舒张心肌硬度在4周、35周和88周时保持不变，心肌的收缩应力-应变关系根据胶原蛋白的结构重塑和疤痕形成而发生有益或有害的改变。因此，在左心室肥厚早期，反应性纤维化和胶原重塑发生在没有坏死的情况下，而后来出现修复性纤维化。在这项研究中，重塑的胶原基质似乎负责在左心室肥厚的各个阶段观察到的力产生的变化。
Cardiac muscle is tethered within a fibrillar collagen matrix that serves to maximize force generation. In the human pressure-overloaded, hypertrophied left ventricle, collagen concentration is known to be increased: however, the structual and biochemical remodeling of collagen and its relation to cell necrosis and myocardial mechanics is less clear. Accordingly, this study was undertaken in a nonhuman primate model of left ventricular hypertrophy caused by gradual onset experimental hypertension. The amount of collagen, its light microscopic features, and proportions of collagen types I, III, and V were determined together with diastolic and systolic mechanics of the intact ventricle during the V were determined together with diastolic and systolic mechanics of the intact ventricle during the evolutionary, early, and late phases of established left ventricular hypertrophy (4, 35, and 88 weeks, repectively). In comparison to controls, we found 1) increased collagen at 4 weeks, as well as a greater proportion of type III, in the absence of myocyte necrosis; 2) collagen septae were thick and dense at 35 weeks, while the proportion of types I and III had converted to control; 3) necrosis was evident at 88 weeks, and the structural remodeling and proportion of collagen types I and III reflected the extent of scar formation; and 4) unlike diastolic myocardial stiffness, which was unchanged at 4,35, or 88 weeks, the systolic stree-strain relation of the myocardium was altered in either a benefical or detrimental manner in accordance with structural remodeling of collagen and scar formation. Thus early in left ventricular hypetrophy, reactive fibrosis and collagen remodeling occur in the absence of necrosis while, later on, reparative fibrosis is present. In this study, the remodeled collagen matrix appeared responsible for variations in force generaton observed during various phases of left ventricular hypertrophy.