Adiponectin reduced H2O2-induced cardiomyocyte hypertrophy and MMP-2 and MMP-9 activities, indicating its cardioprotective role against oxidative stress.
Does adiponectin prevent oxidative stress-induced cardiac remodeling in cultured rat ventricular myocytes and mice?
Adiponectin mediates cardioprotection against oxidative stress-induced remodeling via AMPK activation and inhibition of ERK and NF-κB signaling.
Tasa de eventos absoluta: 0% vs 0%
Reactive oxygen species (ROS) induce matrix metalloproteinase (MMP) activity that mediates hypertrophy and cardiac remodeling. Adiponectin (APN), an adipokine, modulates cardiac hypertrophy, but it is unknown if APN inhibits ROS-induced cardiomyocyte remodeling. We tested the hypothesis that APN ameliorates ROS-induced cardiomyocyte remodeling and investigated the mechanisms involved. Cultured adult rat ventricular myocytes (ARVM) were pretreated with recombinant APN (30 μg/ml, 18 h) followed by exposure to physiologic concentrations of H 2 O 2 (1–200 μM). ARVM hypertrophy was measured by 3 Hleucine incorporation and atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) gene expression by RT-PCR. MMP activity was assessed by in-gel zymography. ROS was induced with angiotensin (ANG)-II (3.2 mg·kg −1 ·day −1 for 14 days) in wild-type (WT) and APN-deficient (APN-KO) mice. Myocardial MMPs, tissue inhibitors of MMPs (TIMPs), p-AMPK, and p-ERK protein expression were determined. APN significantly decreased H 2 O 2 -induced cardiomyocyte hypertrophy by decreasing total protein, protein synthesis, ANF, and BNP expression. H 2 O 2 -induced MMP-9 and MMP-2 activities were also significantly diminished by APN. APN significantly increased p-AMPK in both nonstimulated and H 2 O 2 -treated ARVM. H 2 O 2 -induced p-ERK activity and NF-κB activity were both abrogated by APN pretreatment. ANG II significantly decreased myocardial p-AMPK and increased p-ERK expression in vivo in APN-KO vs. WT mice. ANG II infusion enhanced cardiac fibrosis and MMP-2-to-TIMP-2 and MMP-9-to-TIMP-1 ratios in APN-KO vs. WT mice. Thus APN inhibits ROS-induced cardiomyocyte remodeling by activating AMPK and inhibiting ERK signaling and NF-κB activity. Its effects on ROS and ultimately on MMP expression define the protective role of APN against ROS-induced cardiac remodeling.
Essick et al. (Sat,) reported a other. Adiponectin reduced H2O2-induced cardiomyocyte hypertrophy and MMP-2 and MMP-9 activities, indicating its cardioprotective role against oxidative stress.