Key result
ANGPTL4 attenuates Ang II-induced AF and fibrosis in mice by reversing cardiomyocyte apoptosis.
Why the study?
AF is a major clinical arrhythmia driven by inflammation and fibrosis, but the effects of ANGPTL4 on Ang II-induced AF and its underlying mechanisms were not known.
Does ANGPTL4 attenuate Ang II-induced atrial fibrillation and fibrosis in mice?
Does ANGPTL4 attenuate Ang II-induced atrial fibrillation and fibrosis in mice?
ANGPTL4 attenuates Ang II-induced atrial fibrillation and fibrosis in a mouse model by modulating SIRT3, PPARα, and PPARγ signaling pathways, highlighting a potential therapeutic target.
Hypothesis-generating for ANGPTL4 in AF; leaves open human translation and does not inform practice.
Atrial fibrillation (AF) is the more significant portion of arrhythmia in clinical practice, with inflammation and fibrosis as its central pathological mechanisms. This study aimed to investigate angiopoietin-like 4 (ANGPTL4) effects on angiotensin II- (Ang II-) induced AF and its related pathophysiological mechanisms. C57BL/6J mice were randomized and divided into three groups: the control group, the Ang II group, and the ANGPTL4 group (Ang II with ANGPTL4 treatment). Mice were infused with Ang II (2000 ng/kg/min) and were administrated with recombinant human ANGPTL4 (rhANGPTL4, 20 μg/kg/day) for 3 weeks. The fibrosis was evaluated with Masson’s trichrome staining in the atrial myocardium. mRNA levels of IL-1β, IL-6, collagen I, and collagen III were measured using real-time qRT-PCR. Protein levels of PPARα, PPARγ, CPT-1, and SIRT3 were measured using Western blotting. Compared to the control group, the mice infused with Ang II showed electrocardiogram characteristics of AF, and this effect was markedly attenuated in ANGPTL4-treated mice. ANGPTL4 also reversed the increase in cardiomyocyte apoptosis, inflammation, interstitial collagen fraction, and collagen gene expression in mice with Ang II. Mechanistically, ANGPTL4 inhibited the activation of several fatty acid metabolism-related proteins, including PPARα, PPARγ, and CPT-1, and the expression of SIRT3 protein in atrial tissues. In conclusion, ANGPTL4 attenuates Ang II-induced AF and atrial fibrosis by modulation in the SIRT3, PPARα, and PPARγ signaling pathways.
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Zhu et al. (2021) studied this question. ANGPTL4 treatment significantly attenuated Ang II-induced atrial fibrillation and fibrosis in mice, reversing cardiomyocyte apoptosis and collagen gene expression.
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