Nicotine regulates collagen gene expression, collagenase activity, and DNA synthesis in cultured cardiac fibroblasts.
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 that in 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 micrograms/ml) led to a 31% (P < 0.05) decrease in the abundance of mRNA for pro alpha 1(I) but not pro alpha 2(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.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06510.
R J
RJ
Tomek
S
S
Rimar
M
M
Eghbali-Webb
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics*; D017364:Collagenases / Q000187:drug effects* / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits
D012333:RNA, Messenger; D009538:Nicotine; D003094:Collagen; D004247:DNA; D017364:Collagenases