Wilke A, Funck R, Rupp H, Brilla C G
Zentrum für Innere Medizin, Abteilung Kardiologie, Klinikum der Philipps-Universität, Marburg.
Basic Res Cardiol. 1996;91 Suppl 2:79-84. doi: 10.1007/BF00795367.
The interaction of the renin-angiotensin-aldosterone system (RAAS) and cardiac growth is of great interest in chronic heart failure. The pressure or volume overloaded heart shows a hypertrophic growth of the myocardium, i.e., an enlargement of cardiac myocytes. In addition, 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. This remodeling 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 appearance of symptomatic heart failure. The growth of cardiac fibroblasts is not primarily regulated by the hemodynamic load. In vivo and in vitro studies suggest that the effector hormones, angiotensin II and aldosterone, of the RAAS are primarily involved in regulating the structural remodeling of the myocardial collagen matrix. In cultured adult cardiac fibroblasts, angiotensin II and aldosterone has been shown to stimulate collagen synthesis while angiotensin II additionally inhibits matrix metalloproteinase I activity, which is the key enzyme for interstitial collagen degradation in the myocardium. These findings may serve as rationale for a remedial therapy with angiotensin converting enzyme inhibition or blockage of the RAAS in congestive heart failure in patients with hypertensive heart disease, post myocardial infarction or with dilated cardiomyopathy.
肾素-血管紧张素-醛固酮系统（RAAS）与心脏生长之间的相互作用在慢性心力衰竭中备受关注。压力或容量超负荷的心脏表现出心肌肥厚性生长，即心肌细胞增大。此外，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型纤维状胶原的积聚。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异常，进而引起心室舒张和收缩功能障碍，最终出现有症状的心力衰竭。心脏成纤维细胞的生长并非主要受血流动力学负荷调节。体内和体外研究表明，RAAS的效应激素血管紧张素II和醛固酮主要参与调节心肌胶原基质的结构重塑。在培养的成年心脏成纤维细胞中，血管紧张素II和醛固酮已被证明可刺激胶原合成，而血管紧张素II还可抑制基质金属蛋白酶I的活性，该酶是心肌间质胶原降解的关键酶。这些发现可能为在高血压性心脏病、心肌梗死后或扩张型心肌病患者的充血性心力衰竭中使用血管紧张素转换酶抑制剂或阻断RAAS进行补救治疗提供理论依据。
