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


CONCLUSIONS
Coronary microembolization induces cardiomyocyte apoptosis via the LOX-1-dependent mitochondrial pathway and caspase 8-dependent pathway.
Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Tao
T
Liu
Department of Cardiology, Minzu Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.
You
Y
Zhou
Department of Cardiology, Wuhan Asia Heart Hospital, Wuhan, Hubei, China.
Jiang-You
JY
Wang
Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Qiang
Q
Su
Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Zhong-Li
ZL
Tang
Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Yang-Chun
YC
Liu
Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China drlilang@163.com.
Lang
L
Li
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053181:Caspase 8 / Q000378:metabolism*; D004621:Embolization, Therapeutic / Q000009:adverse effects*; D005260:Female; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013552:Swine; D013556:Swine, Miniature
C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; D053181:Caspase 8
apoptosis; cardiomyocyte; caspase; coronary microembolization; lectin-like oxidized low-density lipoprotein receptor 1