BackgroundResveratrol (Resv) is known to prevent cardiac hypertrophy by a mechanism attributed to direct effects on cardiomyocytes. Cardiac fibroblasts are known to mediate the paracrine induction of hypertrophy, by secreting bioactive agents including the pro‐hypertrophic high molecular weight (Hi) FGF‐2. Here, we examined the effects of Resv on the angiotensin II (Ang II)‐induced HiFGF‐2 upregulation and release by cardiac myofibroblasts.ResultsCardiac non‐myocytes, isolated from the hearts of neonatal rats or from human cardiac atrial tissue, expressed proteins characteristic of myofibroblastic phenotype at passage P2, as indicated by expression of extra domain A‐fibronectin, non‐muscle myosin heavy chain, and α‐smooth muscle actin. Stimulation with Ang II promoted the upregulation of both total and exported HiFGF‐2. Secreted HiFGF‐2 was capable of inducing cardiomyocyte hypertrophy in culture. Resv prevented both total and exported HiFGF‐2 upregulation, in both rat and human heart cells. Studies have shown that the effects of Resv can be mediated by inhibition of ERK and MMP‐2 activities; in agreement, we found that inhibition of these pathways diminished the Ang II‐induced HiFGF2 upregulation and release.ConclusionsOur data suggest that the anti‐hypertrophic effect of Resv may be mediated in part by its effects on cardiac fibroblasts, preventing HiFGF‐2 accumulation and secretion.Grant Funding Source: CIHR