The renin-angiotensin-aldosterone system and myocardial collagen matrix remodelling in congestive heart failure
The renin-angiotensin-aldosterone system and myocardial collagen matrix remodelling in congestive heart failure
复制标题
DOI：
10.1093/eurheartj/16.suppl_o.107
复制
发表时间：
1995-12-01
影响因子：
39.3
通讯作者：
Maisch, B
中科院分区：
文献类型：
--
作者：
Brilla, CG;Rupp, H;Maisch, B
在慢性心力衰竭中，包括Frank-Starling机制、神经激素反应、心脏生长和外周氧输送在内的各种调节系统可能起作用。近年来，肾素-血管紧张素-醛固酮系统（RAAS）与心脏生长的相互关系引起了临床的关注。在压力或容量超负荷的心脏中，心肌细胞生长的发展主要依赖于心室负荷。在不主要受血流动力学负荷调节的情况下，也可能发生涉及心脏成纤维细胞的非心肌细胞生长。心脏成纤维细胞活化是导致I型和III型胶原纤维在心肌内冠状动脉内膜和外膜内积聚的原因。除了由于肌浆Ca 2 +-ATP酶活性受损导致的舒张异常之外，心脏内膜的这种重塑是病理性肥大的主要决定因素，因为它导致异常的心肌僵硬，RAAS的效应激素血管紧张素II（AngII）和醛固酮（Aldo）似乎主要参与促进心肌胶原基质的不利结构重塑。在培养的成人心脏成纤维细胞中，AngII和Aldo已显示刺激胶原蛋白合成，而AngII另外抑制基质金属蛋白酶I活性，基质金属蛋白酶I是心脏纤维组织中纤维胶原蛋白降解的关键酶，这些发现可以作为为什么血管紧张素转换酶抑制或RAAS阻断代表这种补救治疗的原理，仅仅是让充血性心力衰竭患者的心脏卸载。
In chronic heart failure, various regulatory systems including the Frank-Starling mechanism, the neuro-hormonal response, cardiac growth and peripheral oxygen delivery may be operative. Recently, the inter-relationship of the renin-angiotensin-aldosterone system (RAAS) and cardiac growth has drawn clinical interest. In the pressure- or volume-overloaded heart, the development of myocyte growth is primarily dependent on ventricular loading Non-myocyte cell growth involving cardiac fibroblasts may also occur brit this is not primarily regulated by the haemodynamic load. Cardiac fibroblast activation is responsible for the accumulation of fibrillar type I and type III collagens within the interstitium and adventitia of intra-myocardial coronary arteries In addition to relaxation abnormalities due to impairment of sarcoplasmic Ca2+-ATPase activity this remodelling of the cardiac interstitium represents a major determinant of pathological hypertrophy in that it accounts for abnormal myocardial stiffness, leading to ventricular diastolic and systolic dysfunction and ultimately the progression of symptomatic heart failure.The effector hormones of the RAAS, angiotensin II (AngII) and aldosterone (Aldo), appear to be primarily involved in promoting the adverse structural remodelling of the myocardial collagen matrix. In cultured adult cardiac fibroblasts, AngII and Aldo have been shown to stimulate collagen synthesis while AngII additionally inhibits matrix metalloproteinase I activity, which is the key enzyme for degradation of fibrillar collagen in the cardiac interstitium, lending to excessive collagen accumulationThese findings may serve as rationale as to why angiotensin converting enzyme inhibition or blockade of the RAAS represents such remedial therapy beyond the effect of simply unloading the heart in patients with congestive heart failure.