Regulation of the structural remodelling of the myocardium: from hypertrophy to heart failure.
The Framingham heart study has shown that arterial hypertension is the major aetiological factor for the development of heart failure. In the presence of heart failure, various regulatory systems may be operative. These include the Frank-Starling mechanism, the neurohormonal system, regulation of cardiac growth and peripheral oxygen delivery. Recently, the interrelationship of the neuroendocrine system and cardiac growth has been examined. In the pressure or volume overloaded heart, growth of the myocardium involves the enlargement of cardiac myocytes, an adaptation governed by ventricular loading. Non-myocyte cell growth, including cardiac fibroblasts, may also occur. However, the haemodynamic load does not appear to be its major physiological stimulus. Cardiac fibroblast activation is responsible for the accumulation of type I and III collagens, the major fibrillar proteins of the myocardial collagen matrix, while vascular smooth muscle cell growth accounts for medial thickening of coronary resistance vessels. This structural remodelling of the cardiac interstitium represents a major determinant of pathological hypertrophy: it accounts for abnormal myocardial stiffness and impaired coronary reserve, thereby leading to ventricular diastolic and systolic dysfunction and ultimately the appearance of symptomatic heart failure. Several lines of evidence suggest that circulating and tissue renin-angiotensin-aldosterone systems are involved in the structural remodelling of the non-myocyte compartment, including the 'cardioprotective' effects of angiotensin converting enzyme (ACE) inhibition or the beneficial effects of anti-aldosterone treatment that were found to prevent myocardial fibrosis in renovascular hypertension due to unilateral renal ischaemia under experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Brilla
C G
CG
Division of Cardiology, Philipps-University of Marburg, Germany.
Maisch
B
B
D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000473:pathology* / Q000503:physiopathology; D002455:Cell Division / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D004719:Endomyocardial Fibrosis / Q000473:pathology / Q000503:physiopathology; D006333:Heart Failure / Q000473:pathology* / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System / Q000502:physiology
D003094:Collagen