PMID- 37866806
OWN - NLM
STAT- MEDLINE
DCOM- 20231120
LR  - 20231206
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 334
DP  - 2023 Dec 1
TI  - Vericiguat alleviates ventricular remodeling and arrhythmias in mouse models of 
      myocardial infarction via CaMKII signaling.
PG  - 122184
LID - S0024-3205(23)00819-6 [pii]
LID - 10.1016/j.lfs.2023.122184 [doi]
AB  - AIMS: Maladaptive ventricular remodeling is a major cause of ventricular 
      arrhythmias following myocardial infarction (MI) 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 
      MI-induced ventricular remodeling and arrhythmias are not fully comprehended; 
      hence, our research evaluated the effect of vericiguat on mice post-MI. MATERIALS 
      AND METHODS: Mice were divided into four treatment groups: Sham, Sham+Veri, MI, 
      and MI + Veri. For the MI groups and MI + Veri groups, the left anterior 
      descending (LAD) coronary artery was occluded to induce MI. 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 cells were 
      cultured for further mechanistic studies. Assessment methods included 
      echocardiography, pathological analysis, electrophysiological analysis, and 
      Western blotting. KEY FINDINGS: 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 MI-induced calcium/calmodulin-dependent 
      protein kinase II (CaMKII) pathway activation in mice. SIGNIFICANCE: Vericiguat 
      alleviated MI-induced left ventricular adverse remodeling and arrhythmias through 
      modulation of the CamkII signaling pathway.
CI  - Copyright (c) 2023. Published by Elsevier Inc.
FAU - Chen, Tao
AU  - Chen T
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      Hubei, PR China; Cardiovascular Research Institute of Wuhan University, Wuhan 
      430060, Hubei, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei, 
      PR China.
FAU - Kong, Bin
AU  - Kong B
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      Hubei, PR China; Cardiovascular Research Institute of Wuhan University, Wuhan 
      430060, Hubei, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei, 
      PR China.
FAU - Shuai, Wei
AU  - Shuai W
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      Hubei, PR China; Cardiovascular Research Institute of Wuhan University, Wuhan 
      430060, Hubei, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei, 
      PR China.
FAU - Gong, Yang
AU  - Gong Y
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      Hubei, PR China; Cardiovascular Research Institute of Wuhan University, Wuhan 
      430060, Hubei, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei, 
      PR China.
FAU - Zhang, Jingjing
AU  - Zhang J
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      Hubei, PR China; Cardiovascular Research Institute of Wuhan University, Wuhan 
      430060, Hubei, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei, 
      PR China.
FAU - Huang, He
AU  - Huang H
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      Hubei, PR China; Cardiovascular Research Institute of Wuhan University, Wuhan 
      430060, Hubei, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei, 
      PR China. Electronic address: huanghe1977@whu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20231020
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - LV66ADM269 (vericiguat)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
MH  - Ventricular Remodeling
MH  - Quality of Life
MH  - *Myocardial Infarction/complications/drug therapy/metabolism
MH  - Arrhythmias, Cardiac/drug therapy/etiology/metabolism
MH  - Signal Transduction
OTO - NOTNLM
OT  - Calcium/calmodulin-dependent protein kinase II
OT  - Myocardial infarction
OT  - Ventricular arrhythmia
OT  - Ventricular remodeling
OT  - Vericiguat
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/10/23 00:43
MHDA- 2023/11/20 06:54
CRDT- 2023/10/22 19:35
PHST- 2023/06/26 00:00 [received]
PHST- 2023/10/04 00:00 [revised]
PHST- 2023/10/15 00:00 [accepted]
PHST- 2023/11/20 06:54 [medline]
PHST- 2023/10/23 00:43 [pubmed]
PHST- 2023/10/22 19:35 [entrez]
AID - S0024-3205(23)00819-6 [pii]
AID - 10.1016/j.lfs.2023.122184 [doi]
PST - ppublish
SO  - Life Sci. 2023 Dec 1;334:122184. doi: 10.1016/j.lfs.2023.122184. Epub 2023 Oct 
      20.