Weber K T, Jalil J E, Janicki J S, Pick R
Cardiovascular Institute, Michael Reese Hospital, University of Chicago Pritzker School of Medicine, Illinois 60616.
Am J Hypertens. 1989 Dec;2(12 Pt 1):931-40. doi: 10.1093/ajh/2.12.931.
The accumulation of collagen within the myocardium is termed fibrosis. In left ventricular pressure overload a reactive interstitial fibrosis, having distinctive biochemical and structural features, is seen. This reactive fibrosis occurs in the absence of myocyte necrosis, is progressive in nature, and initially is an adaptive response that preserves the force generating capacity, or active (systolic) stiffness, of the hypertrophied myocardium. Later in hypertrophy a reparative (or replacement) fibrosis occurs in response to cell loss, the pathogenesis of which is not clear. Nevertheless, independently of cell loss, interstitial fibrosis can have a detrimental influence on the diastolic and systolic stiffness of the myocardium and can result in pathologic hypertrophy with heart failure. In established hypertrophy with disproportionate collagen matrix remodeling (ie, interstitial heart disease), it would be desirable to retard the continued formation of collagen and, if necessary, degrade collagen fibers that are responsible for impeding the stretching and shortening of muscle fibers. Prevention of interstitial fibrosis in pressure overload hypertrophy with pharmacologic agents with both antihypertensive and antifibrotic properties must also be considered. Future research should address these issues with a view toward developing corrective and preventative forms of therapy. Such advances will require a better understanding of cardiac fibroblast growth, collagen synthesis and the regulation of collagen gene expression in the heart.
心肌内胶原蛋白的积聚被称为纤维化。在左心室压力超负荷时，会出现一种具有独特生化和结构特征的反应性间质纤维化。这种反应性纤维化在没有心肌细胞坏死的情况下发生，本质上是进行性的，最初是一种适应性反应，可保留肥厚心肌的力产生能力或主动（收缩期）僵硬度。在肥厚后期，会出现一种修复性（或替代性）纤维化以应对细胞丢失，其发病机制尚不清楚。然而，与细胞丢失无关，间质纤维化可对心肌的舒张期和收缩期僵硬度产生不利影响，并可导致病理性肥厚伴心力衰竭。在已确立的伴有不成比例的胶原基质重塑（即间质心脏病）的肥厚中，延缓胶原蛋白的持续形成，并在必要时降解阻碍肌纤维伸展和缩短的胶原纤维，将是可取的。还必须考虑使用具有抗高血压和抗纤维化特性的药物预防压力超负荷肥厚中的间质纤维化。未来的研究应以开发纠正性和预防性治疗形式为目标来解决这些问题。这些进展将需要更好地理解心脏成纤维细胞生长、胶原蛋白合成以及心脏中胶原蛋白基因表达的调控。
