Key result
Cardiac fibroblasts isolated from SHRLJ rats using collagenase B or P differ in growth rates, AII receptor binding, AT1A mRNA levels, and morphology compared to WKYLJ fibroblasts.
Cardiac fibroblasts from spontaneously hypertensive rats exhibit distinct growth, receptor expression, and morphological responses compared to normotensive controls, which may be influenced by the isolation method.
Method-dependent fibroblast differences in hypertensive rat models warrant caution interpreting in vitro data; leaves open human translation.
The mechanisms whereby angiotensin converting enzyme inhibitors reverse cardiac remodelling appear to involve angiotensin and/or bradykinin receptors. Previously we reported that cultured rat cardiac fibroblasts express angiotensin II (AII) receptors. In the present study we compared AII receptor binding, gene expression of angiotensinogen and the AII, Subtype 1A (AT1A) receptor, as well as morphological changes induced by selected hormonal treatments in cultured fibroblasts derived from SHRLJ or WKYLJ rats. 2. Fibroblasts were isolated from adult rat left ventricle by either collagenase B or collagenase P digestion. Collagenase B yielded cell preparations from SHRLJ which grew slower than cells from WKYLJ rats and expressed nearly two-fold fewer AII receptors (compared to WKYLJ) while collagenase P yielded SHRLJ cells with similar binding and growth properties to WKYLJ. A good correlation was observed between receptor binding and AII receptor, type 1A (AT1A) mRNA concentrations. In the presence of steroids collagenase B cells showed a higher tendency to transform towards a preadipocyte cell type, estimated by the formation of lipid containing vacuoles/cell, while collagenase P cells, mainly the SHRLJ type, start to differentiate toward a myofibroblast-like cell type in the presence of AII, as calculated by the expression of alpha-smooth muscle actin. 3. From the results obtained in this study it is evident that a subset of fibroblasts can be isolated from the SHRLJ heart using collagenase B or P which differ in growth rates, AII receptor binding, AT1A and angiotensinogen mRNA levels, morphology and steroid responsiveness when compared to fibroblasts isolated from cardiac WKYLJ tissue.
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Klett et al. (1995) studied this question. SHRLJ rat origin and collagenase B or P digestion vs. WKYLJ rat origin was evaluated on AII receptor binding, gene expression of angiotensinogen and AT1A receptor, and morphological changes. Cardiac fibroblasts isolated from SHRLJ rats using collagenase B or P differ in growth rates, AII receptor binding, AT1A mRNA levels, and morphology compared to WKYLJ fibroblasts.
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