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Cigarette smoke attenuates collagen production and migration of cardiac fibroblasts through inhibition of the HIF‐1α pathway
Author(s) -
Bradley Jessica Marie,
Doggett Travis M,
El Hajj Milad,
Pyakurel Kusma,
Breslin Jerome W,
Gardner Jason D
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1059.8
Subject(s) - western blot , extracellular matrix , fibroblast , hydroxyproline , extracellular , cardiac fibrosis , medicine , secretion , microbiology and biotechnology , chemistry , endocrinology , biology , heart failure , biochemistry , in vitro , gene
Cigarette smoke (CS) is the major cause of preventable death with 5 million deaths annually worldwide, many due to cardiovascular disease. Previously, we found that 6 wks of CS exposure exacerbates volume overload cardiac remodeling and dysfunction. Our findings indicated that CS induces ventricular dilation by disrupting compensatory collagen production. Key regulators of extracellular matrix remodeling are the cardiac fibroblasts. Our hypothesis is that CS exposure inhibits the HIF‐1α pathway preventing collagen production and impairing migration of cardiac fibroblasts. We examined the effects of CS using isolated adult rat cardiac fibroblasts. After 24 hrs exposure to 0, 5 and 10% CS extract (CSE), Western blot analysis on whole cell lysates demonstrated that 10% CSE reduced expression of HIF‐1α (13% vs. control) and VEGF (6%), a downstream product of HIF‐1α activation. Collagen secretion assessed by media hydroxyproline was reduced after 5 and 10% CSE by 64 and 72%, respectively. Using electric cell‐substrate impedance sensing (ECIS) to evaluate cardiac fibroblast migration after wounding, we found that 5% CSE had little effect; however, 10% CSE impaired migration by 36%. These data suggest that CS may attenuate collagen production and migration of cardiac fibroblasts through inhibition of the HIF‐1α pathway. Louisiana Board of Regents LEQSF2009‐12‐RDA10, NIH P20RR018766 and R01HL098215.