2. Academic Validation
  3. Chronic mitochondrial dynamic-targeted therapy alleviates left ventricular dysfunction by reducing multiple programmed cell death in post-myocardial infarction rats

Chronic mitochondrial dynamic-targeted therapy alleviates left ventricular dysfunction by reducing multiple programmed cell death in post-myocardial infarction rats

  • Eur J Pharmacol. 2024 Aug 15:977:176736. doi: 10.1016/j.ejphar.2024.176736.
Chanon Piamsiri 1,  Chayodom Maneechote 2,  Kewarin Jinawong 1,  Busarin Arunsak 2,  Titikorn Chunchai 2,  Wichwara Nawara 2,  Sasiwan Kerdphoo 2,  Siriporn C Chattipakorn 3,  Nipon Chattipakorn 4
Affiliations

Affiliations

  • 1 Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand.
  • 2 Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand.
  • 3 Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand; Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, 50200, Thailand.
  • 4 Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand. Electronic address: nchattip@gmail.com.
PMID: 38878877 DOI: 10.1016/j.ejphar.2024.176736
Abstract

Mitochondrial dysfunction and the activation of multiple programmed cell death (PCD) have been shown to aggravate the severity and mortality associated with the progression of myocardial infarction (MI). Although pharmacological modulation of mitochondrial dynamics, including treatment with the fusion promoter (M1) and the fission inhibitor (Mdivi-1), exerted cardioprotection against several cardiac complications, their roles in the post-MI model have never been investigated. Using a MI rat model instigated by permanent left-anterior descending (LAD) coronary artery occlusion, post-MI rats were randomly assigned to receive one of 4 treatments (n = 10/group): vehicle (DMSO 3%V/V), enalapril (10 mg/kg), Mdivi-1 (1.2 mg/kg) and M1 (2 mg/kg), while a control group of sham operated rats underwent surgery without LAD occlusion (n = 10). After 32-day treatment, cardiac and mitochondrial function, and histopathological morphology were investigated and molecular analysis was performed. Treatment with enalapril, Mdivi-1, and M1 significantly mitigated cardiac pathological remodeling, reduced myocardial injury, and improved left ventricular (LV) function in post-MI rats. Importantly, all interventions also attenuated mitochondrial dynamic imbalance and mitigated activation of Apoptosis, Necroptosis, and Pyroptosis after MI. This investigation demonstrated for the first time that chronic mitochondrial dynamic-targeted therapy mitigated mitochondrial dysfunction and activation of PCD, leading to improved LV function in post-MI rats.

Keywords

Heart failure; Mitochondrial dynamics; Mitochondrial fission; Mitochondrial fusion; Myocardial infarction; Programmed cell death.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z