title: Renin-angiotensin system and myocardial fibrosis in hypertension: regulation of the myocardial collagen matrix.
abstract: The cardiac interstitium is composed of non-myocyte cells embedded in a highly organized extracellular matrix containing a three-dimensional collagen network which serves to maintain the architecture of the myocardium and determines myocardial stiffness. In hypertensive heart disease, a heterogeneity in myocardial structure, created by the altered behaviour of cardiac fibroblasts responsible for collagen synthesis and degradation, can explain the appearance of diastolic and ultimately systolic dysfunction of the left ventricle. In vivo, circulating and myocardial renin-angiotensin systems (RAS) were found to be involved in the regulation of the structural remodelling of the cardiac interstitium. In vitro, in cultured adult rat cardiac fibroblasts, angiotensin II was shown to stimulate collagen synthesis and to inhibit collagenase activity, which is the key enzyme for collagen degradation. In the SHR-model of primary hypertension, left ventricular hypertrophy could be regressed and abnormal myocardial diastolic stiffness, due to interstitial fibrosis, could be restored to normal by inhibition of the myocardial RAS. These antifibrotic or cardioreparative effects of ACE inhibition that occurred irrespective of blood pressure normalization may be valuable in reversing left ventricular diastolic dysfunction in hypertensive heart disease.
authors.affiliation: Division of Cardiology, Philipps-University of Marburg, Germany.
authors.forename: C G
authors.initials: CG
authors.lastname: Brilla
authors.forename: G P
authors.initials: GP
authors.lastname: Reams
authors.forename: B
authors.initials: B
authors.lastname: Maisch
authors.forename: K T
authors.initials: KT
authors.lastname: Weber
mesh_terms: D000818:Animals; D003094:Collagen / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology*; D005355:Fibrosis; D006321:Heart / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D003094:Collagen