Brilla C G, Rupp H, Funck R, Maisch B
Department of Internal Medicine, Philipps University of Marburg, Germany.
Eur Heart J. 1995 Dec;16 Suppl O:107-9. doi: 10.1093/eurheartj/16.suppl_o.107.
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 but 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 intramyocardial coronary arteries. In addition to relaxation abnormalities due to impairment of sarcoplasmic Ca(2+)-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, leading to excessive collagen accumulation. These 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.
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发挥作用。最近，肾素-血管紧张素-醛固酮系统（RAAS）与心脏生长之间的相互关系引起了临床关注。在压力或容量超负荷的心脏中，心肌细胞生长的发展主要取决于心室负荷。涉及心脏成纤维细胞的非心肌细胞生长也可能发生，但这并非主要由血流动力学负荷调节。心脏成纤维细胞的激活导致心肌内冠状动脉间质和外膜中I型和III型纤维状胶原的积累。除了由于肌浆网Ca(2+)-ATP酶活性受损导致的舒张异常外，心脏间质的这种重塑是病理性肥大的主要决定因素，因为它导致心肌僵硬度异常，进而导致心室舒张和收缩功能障碍，最终导致症状性心力衰竭的进展。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良结构重塑。在培养的成年心脏成纤维细胞中，AngII和Aldo已被证明可刺激胶原合成，而AngII还可抑制基质金属蛋白酶I的活性，基质金属蛋白酶I是心脏间质中纤维状胶原降解的关键酶，导致胶原过度积累。这些发现可以解释为什么在充血性心力衰竭患者中，血管紧张素转换酶抑制或RAAS阻断除了单纯减轻心脏负荷的作用外，还具有治疗作用。
