Inhibitory effect of nicotine on collagen and alpha‐smooth muscle actin expression in cardiac fibroblasts

Abstract

It is well documented that smoking increases risk of cardiovascular disease and myocardial infarction (MI). Extra‐cellular matrix (ECM) protein deposition by cardiac fibroblasts (CF) is a hallmark of post‐MI scarring and wound healing. In this study, we used primary cultures of rat CF (rCF) to assess the effect of nicotine (Nic) on ECM production by CF. We treated rCF with 1 μM nicotine in the absence and presence of 10 ng/ml transforming growth factor beta (TGF‐β), a cytokine that induces CF to produce ECM proteins. Quantitative real‐time PCR revealed that TGF‐β treatment induces a 2‐fold increase in expression of collagen1a1 (Col1a1) and alpha‐smooth muscle actin (α‐SMA) mRNA. Nic alone had no effect on “basal” Col1a1 or α‐SMA expression but abolished the TGF‐β induced increases in Col1a1 and α‐SMA mRNA. These results suggest that Nic has an inhibitory effect on damage‐induced ECM protein production of rCF. The findings imply that Nic intake through smoking of tobacco or other sources may inhibit wound healing and scar tissue formation in the heart following cardiac damage (e.g., post‐MI) by inhibiting collagen synthesis and myofibroblast transformation. Such inhibition may contribute to smoking‐induced exacerbation of cardiovascular disease and damage. (Supported by grants from NIH and the Ellison Medical Foundation).