Role of angiotensin II and prostaglandin E2 in regulating cardiac fibroblast collagen turnover

Christian G. Brilla, Guoping Zhou, Heinz Rupp, Bernhard Maisch, Karl Weber

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

In hypertensive heart disease, after myocardial infarction or in congestive heart failure, myocardial fibrosis presenting as a diffuse perivascular and interstitial accumulation of fibrillar collagens within the normal connective tissue structures of the myocardium is associated with an activated renin- angiotensin system (RAS). This reactive fibrosis occurs in the overloaded left ventricle and the nonoverloaded right ventricle irrespective of myocyte necrosis or the development of myocyte hypertrophy. Therefore, it appears that hemodynamic factors or the load of the ventricle are not primarily responsible for the adverse fibrous tissue response in the myocardium, and humoral factors may play a key role in regulating the myocardial collagen matrix. The neurohumoral response in hypertensive heart disease, after myocardial infarction with overall deterioration of left ventricular function or congestive heart failure leads to an activation of either the cardiac or the circulating RAS, which closely interacts with the bradykinin-prostaglandin system. To ascertain whether the RAS effector hormone angiotensin II or prostaglandin E2 (PGE2) directly modulates collagen synthesis or degradation in adult human cardiac fibroblasts that express mRNAs for types I and III collagens (the major fibrillar collagens in the heart) and matrix metalloproteinase 1 (MMP1 ; the key enzyme for collagen degradation), collagen synthesis was measured by [3H]proline incorporation normalized to total protein synthesis and MMP1 activity was determined by degradation of [14C]collagen in cultured fibroblasts after 24-hour incubation with various concentrations of angiotensin II or PGE2 (10-11-10-3 M) under serum-free conditions. In addition, effects of angiotensin II were evaluated in the presence or absence of either type 1 (ICI D8731) or type 2 (PD 123177) angiotensin II (AT, or AT2) receptor antagonists, respectively. Under these culture conditions, angiotensin II significantly stimulates collagen synthesis in a dose-dependent manner involving predominantly AT1 receptors. In addition, angiotensin II inhibits MMP1 activity. In contrast, PGE2 down-regulates collagen synthesis and increases collagen degradation. These findings suggest a direct interaction between the RAS effector hormone, angiotensin II, and cardiac fibroblasts in mediating myocardial fibrosis, whereas PGE2, a key mediator of the bradykinin-prostaglandin system, appears to counteract the influence of RAS on myocardial collagen turnover.

Original languageEnglish (US)
Pages (from-to)8D-13D
JournalThe American journal of cardiology
Volume76
Issue number13 SUPPL. 1
DOIs
StatePublished - Nov 2 1995
Externally publishedYes

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Dinoprostone
Angiotensin II
Collagen
Fibroblasts
Renin-Angiotensin System
Fibrillar Collagens
Fibrosis
Bradykinin
Muscle Cells
Heart Ventricles
Prostaglandins
Heart Diseases
Myocardium
Heart Failure
Myocardial Infarction
Angiotensin Type 2 Receptor
Hormones
Matrix Metalloproteinase 1
Angiotensin Receptors
Collagen Type III

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Role of angiotensin II and prostaglandin E2 in regulating cardiac fibroblast collagen turnover. / Brilla, Christian G.; Zhou, Guoping; Rupp, Heinz; Maisch, Bernhard; Weber, Karl.

In: The American journal of cardiology, Vol. 76, No. 13 SUPPL. 1, 02.11.1995, p. 8D-13D.

Research output: Contribution to journalArticle

Brilla, Christian G. ; Zhou, Guoping ; Rupp, Heinz ; Maisch, Bernhard ; Weber, Karl. / Role of angiotensin II and prostaglandin E2 in regulating cardiac fibroblast collagen turnover. In: The American journal of cardiology. 1995 ; Vol. 76, No. 13 SUPPL. 1. pp. 8D-13D.
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