Maladaptive ventricular remodeling is a major cause of ventricular arrhythmias following myocardial infarction and adversely impacts the quality of life of affected patients. Vericiguat is a new soluble guanylate cyclase (sGC) activator with cardioprotective properties. However, its effects on myocardial infarction-induced ventricular remodeling and arrhythmias are not fully comprehended; hence, our research evaluated the effect of vericiguat on mice post-myocardial infarction.
Mice were divided into four treatment groups: Sham, Sham+Veri, MI, and MI + Veri. For the MI groups, the left anterior descending coronary artery was occluded to induce myocardial infarction. Conversely, the Sham group underwent mock surgery. Vericiguat was administered orally daily for 28 days to the Sham+Veri and MI + Veri groups. Additionally, H9c2 cardiomyocytes were cultured for further mechanistic studies. Assessment methods included echocardiography, pathological analysis, electrophysiological analysis, and Western blotting.
Vericiguat reduced cardiac dysfunction and infarct size after MI. It also mitigated MI-induced left ventricular fibrosis and cardiomyocyte apoptosis. Vericiguat normalized the expression of ion channel proteins (Kv4.3, Kv4.2, Kv2.1, Kv1.5, Kv7.1, KCNH2, Cav1.2) and the gap junction protein connexin 43, reducing the susceptibility to ventricular arrhythmia. Vericiguat significantly inhibited myocardial infarction-induced calcium/calmodulin-dependent protein kinase II (CaMKII) pathway activation in mice.
Vericiguat alleviated myocardial infarction-induced left ventricular adverse remodeling and arrhythmias through modulation of the CamkII signaling pathway.

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