Coronary Microembolization Induces Cardiomyocyte Apoptosis in Swine by Activating the LOX-1-Dependent Mitochondrial Pathway and Caspase-8-Dependent Pathway

J Cardiovasc Pharmacol Ther. 2016 Mar;21(2):209-18. doi: 10.1177/1074248415599265. Epub 2015 Aug 14.

Abstract

Background: Cardiomyocyte apoptosis by coronary microembolization (CME) contributes to myocardial dysfunction, in which mitochondrial pathway and death receptor pathway are activated. Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) is a membrane protein involved in apoptosis. The study aimed to explore the role of LOX-1 in the activation of these 2 major apoptotic pathways.

Methods: Twenty Bama miniature swine were randomized into 4 groups (n = 5 per group). The groups were Sham, CME, LOX-1 small-interfering RNA (siRNA), and control siRNA. Microspheres were injected into the left anterior descending artery of swine to establish CME model. Twelve hours after operation, cardiac function, serum c-troponin I level, microinfarct, and apoptotic index were examined. The levels of LOX-1, Bcl-2, Bax, cytochrome c as well as cleaved caspase 9, -8, and -3 were detected.

Results: Myocardial dysfunction, enhanced serum c-troponin I, microinfarct, and apoptosis were induced following CME. Moreover, CME induced increased expression of LOX-1, Bax, cytochrome c, cleaved caspase 9, -8, and -3 as well as decreased Bcl-2 expression levels. The LOX-1 siRNA reversed these effects by CME except cleaved caspase 8 expression, while the control siRNA had no effect.

Conclusion: Coronary microembolization induces cardiomyocyte apoptosis via the LOX-1-dependent mitochondrial pathway and caspase 8-dependent pathway.

Keywords: apoptosis; cardiomyocyte; caspase; coronary microembolization; lectin-like oxidized low-density lipoprotein receptor 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Caspase 8 / metabolism*
  • Embolization, Therapeutic / adverse effects*
  • Female
  • Male
  • Microvessels / metabolism
  • Microvessels / pathology
  • Mitochondria / metabolism*
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Scavenger Receptors, Class E / metabolism*
  • Signal Transduction / physiology
  • Swine
  • Swine, Miniature

Substances

  • OLR1 protein, human
  • Scavenger Receptors, Class E
  • Caspase 8