Significance of hypoxia-inducible factor-1α expression with atrial fibrosis in rats induced with isoproterenol.
Atrial interstitial fibrosis plays a dual role in inducing and maintaining atrial fibrillation (AF). Hypoxia-inducible factor-1α (HIF-1α) has been reported as closely associated with renal, liver and pulmonary fibrosis diseases. However, whether HIF-1α is involved in myocardial fibrosis, and the associations between HIF-1α, transforming growth factor-β1(TGF-β1) and matrix metalloproteinase-9 (MMP-9) remain unknown. Therefore, this area warrants studying for the significance of AF diagnosis and treatment. The present study investigated the expression of HIF-1α in atrial fibrosis and its possible mechanism in isoproterenol (ISO)-induced rats. The three groups of rats; control, ISO and ISO plus sirolimus [also known as rapamycin (Rapa)], were treated for 15 days and sacrificed to remove the myocardial tissues. The expression levels of HIF-1α, TGF-β1and MMP-9 and their associations with atrial fibrosis were examined through histomorphology and protein and mRNA levels. The protein and mRNA levels of HIF-1α, TGF-β1and MMP-9 in the ISO group were increased markedly (P<0.01) compared with the control group, while those in the Rapa group were clearly decreased (P<0.01) compared with the ISO group. The protein and mRNA levels of HIF-1α, TGF-β1and MMP-9 were positively correlated (P<0.01) with atrial fibrosis (collagen volume fraction index), as were theHIF-1α,TGF-β1andMMP-9mRNA levels (P<0.01) and the mRNA levels betweenMMP-9andTGF-β1(P<0.01). During the process of atrial fibrosis in ISO-induced rats, HIF-1α promotes the expression of TGF-β1and MMP-9 protein, and thus is involved in in atrial fibrosis.
Department of Cardiology, Lanzhou General Hospital, People's Liberation Army, Lanzhou, Gansu 730050, P.R. China.
Fangju
F
Su
Department of Cardiology, Lanzhou General Hospital, People's Liberation Army, Lanzhou, Gansu 730050, P.R. China.
Weize
W
Zhang
Department of Cardiology, Lanzhou General Hospital, People's Liberation Army, Lanzhou, Gansu 730050, P.R. China.
Yongqing
Y
Chen
Department of Cardiology, Lanzhou General Hospital, People's Liberation Army, Lanzhou, Gansu 730050, P.R. China.
Ling
L
Ma
Department of Cardiology, Lanzhou General Hospital, People's Liberation Army, Lanzhou, Gansu 730050, P.R. China.
Hanping
H
Zhang
Department of Cardiology, Lanzhou General Hospital, People's Liberation Army, Lanzhou, Gansu 730050, P.R. China.
Fei
F
Wang
atrial; fibrosis; hypoxia inducible factor-1α; matrix metalloproteinase-9; transforming growth factor-β1