Key result
Treatment with the ALDH2 activator Alda-1 reduced cardiac fibrosis and improved left ventricular remodeling parameters in a rat model of myocardial infarction.
Why the study?
Does ALDH2 activation with Alda-1 reduce cardiac fibrosis and improve left ventricular remodeling in a rat model of myocardial infarction?
Does ALDH2 activation with Alda-1 reduce cardiac fibrosis and improve left ventricular remodeling in a rat model of myocardial infarction?
ALDH2 activation with Alda-1 attenuates post-myocardial infarction cardiac fibrosis and adverse remodeling in rats, likely by modulating the Wnt/β-catenin signaling pathway.
ALDH2 activation merits further preclinical testing post-MI; hypothesis-generating in rats and should not yet inform practice.
BACKGROUND: Aldehyde dehydrogenase-2 (ALDH2) has a protective effect on ischemic heart disease. Here, we examined the protective effects of ALDH2 on cardiac fibrosis through modulation of the Wnt/β-catenin signaling pathway in a rat model of myocardial infarction (MI). METHODS: Wistar rats were divided into the sham (control), MI (model), and ALDH2 activator (Alda-1) groups. After 10 days of treatment, the left ventricular (LV) remodeling parameters of each animal were evaluated by echocardiography. Myocardial fibrosis was evaluated by Masson's trichrome staining and Sirius Red staining. Expression levels of collagen types I and III and α-smooth muscle actin (α-SMA) were examined. Finally, the expression and activity of ALDH2 and the levels of several Wnt-related proteins and genes, such as phosphoglycogen synthase kinase (GSK)-3β, GSK-3β, β-catenin, Wnt-1, WNT1-inducible signaling-pathway protein 1, and tumor necrosis factor (TNF)-α, were also analyzed. RESULTS: After MI, the heart weight/body weight ratio, LV dimension at end diastole, and LV dimension at end systole were decreased, while the LV ejection fraction and LV fractional shortening were increased in the Alda-1 group. Myocardial fibrosis was also reduced in the Alda-1 group, accompanied by decreased expression collagen types I and III and α-SMA. β-Catenin, phosphorylated GSK-3β, and Wnt-1 levels were significantly increased in the model group. Interestingly, this alteration was partly reversed by Alda-1 treatment. Immunohistochemical staining showed that numerous WNT1-inducible signaling-pathway protein 1 (WISP-1)- and TNF-α-positive cells were found in the model group. However, few WISP-1- and TNF-α-positive cells were detected in the Alda-1 group. CONCLUSION: The reduction of cardiac fibrosis and the down-regulation of β-catenin, phosphorylated GSK-3β, Wnt-1, and WISP-1 may be mediated by increased ALDH2 activity, leading to reduction of MI-related cardiac fibrosis.
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Zhou et al. (2015) studied Myocardial infarction. ALDH2 activator (Alda-1) vs. Sham (control) and MI (model) was evaluated on Left ventricular remodeling parameters and myocardial fibrosis. Treatment with the ALDH2 activator Alda-1 reduced cardiac fibrosis and improved left ventricular remodeling parameters in a rat model of myocardial infarction.
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