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A Model of Disturbed Flow-Induced Atherosclerosis in Mouse Carotid Artery by Partial Ligation and a Simple Method of RNA Isolation from Carotid Endothelium
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Atherogenic L5 LDL induces cardiomyocyte apoptosis and inhibits KATP channels through CaMKII activation

Yanzhuo Ma1,2, Nancy Cheng2, Junping Sun2

  • 1Department of Cardiology, Bethune International Peace Hospital, 398 Zhongshan Xilu, Shijiazhuang, 050082, Hebei, China.

Lipids in Health and Disease
|August 23, 2020
PubMed
Abstract

Insights

Aberrant L5 low-density lipoprotein (LDL) induces cardiomyocyte apoptosis and arrhythmia by activating CaMKII and impairing KATP channels. This finding clarifies L5

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Cellular Physiology

Background:

  • Cardiac Ca2+/calmodulin-dependent protein kinase II (CaMKII) activation is crucial in cardiomyocyte (CM) apoptosis and arrhythmia.
  • Functional ATP-sensitive potassium (KATP) channels are vital for cardiac protection during ischemia.
  • Aberrant L5 low-density lipoprotein (LDL), a pro-atherogenic form, is elevated in cardiovascular diseases and linked to CM apoptosis and QTc prolongation.

Purpose of the Study:

  • To investigate the role of L5 in cardiac injury.
  • To evaluate the effects of L5 on CaMKII activity in CMs.
  • To assess L5's impact on KATP channel physiology in CMs.

Main Methods:

  • Neonatal rat CMs (NRCMs) were treated with L5 or L1 (control LDL subfraction).
  • Apoptosis, viability, CaMKII activity, and protein expression (phosphorylated CaMKIIδ, NOX2/gp91phox) were assessed.
  • KATP channel function and action potentials (APs) were analyzed using patch-clamp techniques.

Main Results:

  • L5 significantly induced CM apoptosis and reduced viability, unlike L1.
  • L5 decreased Kir6.2 expression and KATP current (IKATP) density, prolonging AP duration.
  • L5 increased CaMKII activity, CaMKIIδ phosphorylation, and NOX2/gp91phox expression.
  • L5-induced apoptosis was mitigated by CaMKII inhibition and reactive oxygen species scavenging.

Conclusions:

  • L5, but not L1, damages CMs by activating the CaMKII pathway.
  • L5 increases cardiac arrhythmogenicity by modulating AP duration.
  • These findings elucidate the detrimental effects of L5 in cardiovascular disease.
Keywords:
ATP-sensitive potassiumAction potentialCa2+/calmodulin-dependent protein kinase IICardiomyocytesElectronegative low-density lipoprotein

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