Angiotensin II type1 receptor regulation and differential trophic effects on rat cardiac myofibroblasts after acute myocardial infarction

Abstract

Fibroblast growth in the scar and surviving tissue is a key element of the remodeling post myocardial infarction. The regulation of fibroblast growth after acute myocardial infarction remains to be determined. Recently, Angiotensin II has been demonstrated to be a mitogen for neonatal cardiac fibroblasts. In this study adult rat cardiac fibroblasts were isolated from different regions of the infarcted rat heart and Angiotensin II effects examined. Adult Wistar-rats were sham operated or left coronary artery ligated. After 4 days, hearts were removed and fibroblasts from sham operated, infarct- and non-infarct regions of the left ventricle isolated. Radioligand binding studies were performed and cell number, cell area, total protein, and AT(1) receptor mRNA after stimulation determined. Radioligand binding studies demonstrated that myofibroblasts expressed a single class of high affinity Angiotensin II AT(1) receptors. Myofibroblasts from the infarct area revealed a lower maximal binding capacity, compared to sham operated myocardium. Conversely, myofibroblasts from the non-infarct area had a higher expression of Angiotensin II AT(1) receptor mRNA compared to sham operated myofibroblasts. Angiotensin II (1 microM, 48 h) increased cell-number in sham operated and non-infarct, but not in infarct myofibroblasts. Angiotensin II elevated total protein in sham operated, non-infarct, and infarct myofibroblasts. In addition, Angiotensin II increased cell area in sham operated and infarct myofibroblasts. These data demonstrate that Angiotensin II acted as a mitogen in sham operated and non-infarct myofibroblasts and stimulated hypertrophy in infarct myofibroblasts. These regional different effects of Angiotensin II might participate in the remodeling post myocardial infarction.

Adenylyl cyclase activity and function are decreased in rat cardiac fibroblasts after myocardial infarction

“…In a MI model, a previous study (32) has shown that the in vivo CF phenotype is stable and can be studied in culture up to passage 4. The methodologies presented here are consistent with previous reports examining protein expression and signaling by CFs isolated from rats after MI and studied in culture (3,15,16,30). However, unlike these studies, which examined CFs at early time points (Յ4 wk) post-MI, we examined the long-term effects of MI on AC function and collagen production to understand the role of AC in CF function in the late phase of remodeling.…”

Macrophage-Stimulated Cardiac Fibroblast Production of IL-6 Is Essential for TGF β/Smad Activation and Cardiac Fibrosis Induced by Angiotensin II

“…Moreover, TGF-β1-induced IL-6 expression participated in trans-differentiation of fibroblasts to myofibroblasts [16]. In the myocardium, activated myofibroblasts are the main source of extracellular matrix proteins such as collagen I/III and fibronectin [17], [18], [19].…”

Identification of Differentially Expressed Genes Induced by Angiotensin Ii in Rat Cardiac Fibroblasts

“…Cardiac remodelling is associated with increased cardiac mass, the accumulation of interstitial collagen and decreased cardiac contractility 1,2 . During the process of cardiac remodelling, cardiac fibroblasts (CF), most of the non‐myocyte cells in the heart, undergo proliferation, differentiation and produce more extracellular matrix (ECM) proteins 3,4 . A variety of extracellular stimuli, such as mechanical stretch and some cytokines, activate cardiac fibroblasts, which are the source of most of the cardiac ECM and many cytokines.…”

“…1,2 During the process of cardiac remodelling, cardiac fibroblasts (CF), most of the non-myocyte cells in the heart, undergo proliferation, differentiation and produce more extracellular matrix (ECM) proteins. 3,4 A variety of extracellular stimuli, such as mechanical stretch and some cytokines, activate cardiac fibroblasts, which are the source of most of the cardiac ECM and many cytokines. Cardiac fibroblasts are able to secrete transforming growth factor (TGF)-b1, endothelin (ET)-1, nitric oxide (NO), platelet-derived growth factor (PDGF)-A and so on.…”