Molecular and Cellular Biochemistry

, Volume 136, Issue 2, pp 97–103 | Cite as

Nicotine regulates collagen gene expression, collagenase activity, and DNA synthesis in cultured cardiac fibroblasts

  • Ronald J. Tomek
  • Stephen Rimar
  • Mahboubeh Eghbali-Webb
Article

Abstract

Cardiac fibroblasts that reside in the interstitium are the cellular origin of collagen and other proteins of the extracellular matrix in the heart. We have previously shown thatin vitro gene expression, proliferation and even phenotypic features of cardiac fibroblasts are subject to regulation by biological factors such as hormones, growth factors and neurotransmitters. The influence of nicotine, the active ingredient of tobacco, on risk factors for cardiac diseases is well known.In vivo adverse effects of nicotine are as the result of its direct and indirect effects. The cellular and molecular mechanisms of direct effects of nicotine in the heart are widely unknown. The objective of this study was to investigate if nicotine has direct influence on cardiac fibroblasts. To this end, we studied the effects of nicotine on cultured cardiac fibroblasts. Northern hybridization analysis of RNA extracted from cardiac fibroblasts, enzymography of conditioned medium of cardiac fibroblasts and [3H]-thymidine incorporation into DNA of cardiac fibroblasts were used to examine the effects of nicotine on collagen gene expression, collagenase activity and DNA synthesis respectively. Treatment of cardiac fibroblasts with nicotine (10 μg/ml) led to a 31% (P<0.05) decrease in the abundance of mRNA for pro α1(I) but not pro α2(I) collagen compared with control untreated cells. Nicotine treatment of cardiac fibroblasts also led to decreased collagenase activity (62%, P<0.001) in the conditioned medium of those cells in culture. Studies with [3H]-thymidine incorporation into DNA of cardiac fibroblasts showed a nicotine-induced decrease (39%, P<0.001) in DNA synthesis in those cells. These findings suggest that cardiac fibroblasts are targets for the toxic effects of nicotine. The findings further point to the possibility that nicotine-induced alterations in cardiac fibroblasts' function and gene expression may contribute to the biological processes that ultimately lead to adverse effects of nicotine in the heart.

Key words

fibroblasts collagen metabolism heart smoking DNA synthesis extracellular matrix tobacco 

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Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • Ronald J. Tomek
    • 1
  • Stephen Rimar
    • 1
  • Mahboubeh Eghbali-Webb
    • 1
  1. 1.Department of AnesthesiologyYale University School of MedicineNew HavenUSA

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