Pharmacological modulation of cardiac fibroblast function

C. G. Brilla, B. Maisch, H. Rupp, R. Funck, G. Zhou, Karl Weber

Research output: Contribution to journalReview article

32 Citations (Scopus)

Abstract

The cardiac interstitium is composed of nonmyocyte cells and a structural protein network which plays a dominant role in governing the structure, architecture, and mechanical behavior of the myocardium. The heterogeneity in myocardial structure, created by the altered behavior of nonmyocyte cells, particularly cardiac fibroblasts which are responsible for myocardial collagen metabolism and fibrous tissue accumulation, may largely explain the appearance of diastolic and/or systolic myocardial failure. Regulatory mechanisms that are related to the fibrous tissue response in various cardiovascular diseases, e.g., hypertensive heart disease, dilated cardiomyopathy or post myocardial infarction, are of primary clinical interest. A better understanding of the hitherto neglected role of cardiac fibroblasts in mediating an adverse structural remodeling of the myocardium will lead to specific pharmacologic agents that interfere with the fibrous tissue response. Several lines of evidence based on in vivo and in vitro studies suggest that circulating and tissue renin-angiotensin-aldosterone systems (RAAS) are involved in the structural remodeling of the nonmyocyte compartment, including the cardioprotective effects of angiotensin converting enzyme (ACE) inhibition or aldosterone receptor antagonism that was found to prevent myocardial fibrosis in the rat with renovascular or genetic hypertension. In cultured adult cardiac fibroblasts, an angiotensin (Ang)II- or aldosterone-mediated dose-dependent increase in collagen synthesis could be completely abolished by the use of AngII type 1 or mineralocorticoid receptor antagonists, respectively. Likewise, the AngII-mediated decrease in the activity of matrix metalloproteinase 1, the key enzyme for interstitial collagen degradation, could be antagonized by AngII receptor blockade. In the rat with genetic hypertension, established left ventricular hypertrophy and abnormal myocardial diastolic stiffness due to interstitial fibrosis, RAAS inhibition resulted in restoration of myocardial structure and function to normal. Likewise, in renovascular hypertension myocardial fibrosis could be regressed by chronic ACE inhibition. These cardioreparative effects of ACE inhibitors may be valuable in improving left ventricular dysfunction in hypertensive heart disease, dilated cardiomyopathy or following myocardial infarction in man.

Original languageEnglish (US)
Pages (from-to)127-134
Number of pages8
JournalHerz
Volume20
Issue number2
StatePublished - Jan 1 1995

Fingerprint

Fibroblasts
Pharmacology
Fibrosis
Collagen
Dilated Cardiomyopathy
Peptidyl-Dipeptidase A
Renin-Angiotensin System
Heart Diseases
Myocardium
Myocardial Infarction
Hypertension
Mineralocorticoid Receptor Antagonists
Mineralocorticoid Receptors
Renovascular Hypertension
Matrix Metalloproteinase 1
Left Ventricular Dysfunction
Left Ventricular Hypertrophy
Aldosterone
Angiotensin-Converting Enzyme Inhibitors
Angiotensin II

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Brilla, C. G., Maisch, B., Rupp, H., Funck, R., Zhou, G., & Weber, K. (1995). Pharmacological modulation of cardiac fibroblast function. Herz, 20(2), 127-134.

Pharmacological modulation of cardiac fibroblast function. / Brilla, C. G.; Maisch, B.; Rupp, H.; Funck, R.; Zhou, G.; Weber, Karl.

In: Herz, Vol. 20, No. 2, 01.01.1995, p. 127-134.

Research output: Contribution to journalReview article

Brilla, CG, Maisch, B, Rupp, H, Funck, R, Zhou, G & Weber, K 1995, 'Pharmacological modulation of cardiac fibroblast function', Herz, vol. 20, no. 2, pp. 127-134.
Brilla CG, Maisch B, Rupp H, Funck R, Zhou G, Weber K. Pharmacological modulation of cardiac fibroblast function. Herz. 1995 Jan 1;20(2):127-134.
Brilla, C. G. ; Maisch, B. ; Rupp, H. ; Funck, R. ; Zhou, G. ; Weber, Karl. / Pharmacological modulation of cardiac fibroblast function. In: Herz. 1995 ; Vol. 20, No. 2. pp. 127-134.
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