Erne P
Abteilung Kardiologie, Kantonsspital Luzern.
Praxis (Bern 1994). 1996 Feb 20;85(8):227-33.
Left-ventricular hypertrophy is the result of cardiac adaptation to global or regional overstress and represents an important cardiovascular risk factor, increasing the risk for development of congestive heart failure and incidence of sudden death. This review describes the pathophysiological and biochemical mechanisms involved in the development of left-ventricular hypertrophy and cardiac fibrosis with particular emphasis on the role of angiotensin II and aldosterone. Central to the cascade of cardiac fibrosis is the increased production or reduced degradation of collagen proteins in fibroblasts. Collagen proteins are proteins needed for the alignment of cellular compartments and the development of forces, contraction and relaxation of the heart. If overexpressed, an important rise of wall stiffness is observed in addition to a reduced capacity to provide oxygen to the cardiac tissue. This latter explains why in areas of histologically hypertrophied heart muscle atrophied muscle cells are observed. The characterization of the second-messenger systems involved in the regulation of cardiac cells as well as the identification of angiotensin-II receptor subtype and angiotensin IV is described. Both of these receptors are present on cardiac fibroblasts and stimulate these to collagen production, which can be inhibited by antagonists or the generation of angiotensin II by ACE inhibitors. In some forms of left-ventricular hypertrophy and in patients with congestive heart failure in addition to elevated angiotensin-II levels, increased aldosterone levels are observed. Aldosterone raises upon stimulation by angiotensin II and upon reduction of angiotensin-II generation subsequent to ACE inhibition through an escape mechanism. The contribution of aldosterone to left-ventricular hypertrophy and cardiac fibrosis can be prevented and reduced by the administration of its antagonist, spironolactone. Further and larger clinical trials are needed and in progress to evaluate if the combination of an ACE inhibitor with spironolactone potentiates the reduction of left-ventricular hypertrophy and if this translates in a reduction of the cardiovascular risk.
左心室肥厚是心脏对整体或局部过度应激的适应性结果，是一个重要的心血管危险因素，会增加发生充血性心力衰竭的风险和猝死的发生率。本综述描述了左心室肥厚和心脏纤维化发生过程中涉及的病理生理和生化机制，特别强调了血管紧张素II和醛固酮的作用。心脏纤维化级联反应的核心是成纤维细胞中胶原蛋白生成增加或降解减少。胶原蛋白是细胞区室排列以及心脏收缩和舒张所需的蛋白质。如果过度表达，除了向心脏组织供氧能力降低外，还会观察到壁僵硬度显著增加。这就解释了为什么在组织学上肥厚的心肌区域会观察到萎缩的心肌细胞。本文还描述了参与调节心脏细胞的第二信使系统的特征以及血管紧张素II受体亚型和血管紧张素IV的鉴定。这两种受体都存在于心脏成纤维细胞上，并刺激其产生胶原蛋白，而拮抗剂或ACE抑制剂产生的血管紧张素II可抑制这种作用。在某些形式的左心室肥厚以及充血性心力衰竭患者中，除了血管紧张素II水平升高外，还观察到醛固酮水平升高。醛固酮在血管紧张素II刺激下以及通过逃逸机制在ACE抑制后血管紧张素II生成减少时升高。通过给予醛固酮拮抗剂螺内酯，可以预防和减少醛固酮对左心室肥厚和心脏纤维化的影响。需要并正在进行进一步的大规模临床试验，以评估ACE抑制剂与螺内酯联合使用是否能增强左心室肥厚的减轻效果，以及这是否能转化为心血管风险的降低。
