Effect of inhibiting malonyl-CoA decarboxylase on cardiac remodeling after myocardial infarction in rats.
OBJECTIVE
The objective of this study was to determine the effect of inhibiting malonyl-CoA decarboxylase (MCD) on cardiac remodeling following myocardial infarction (MI) in rats. We used an ultrasound (US)-mediated microbubble (MB) approach for targeted delivery of a microRNA (miRNA) interference plasmid to the myocardium to silence MCD expression.


METHODS
Five pairs of RNA interference sequences were screened and ranked according to their highest inhibition rates in HEK293 cells. The plasmid with the highest inhibition rate was transfected by US into the rat myocardium after mixing with lipid MB. Twelve and 16 weeks after MI, cardiac function was measured by echocardiography, and glucose transporter-4 (GLUT-4) and high-energy phosphate levels were monitored in the myocardium before and after transfection.


RESULTS
Ejection fraction (EF) decreased by 16% in the control MI group, while it decreased by 8% in the MCD inhibition group that utilized the US-mediated MB approach. Concomitant with the improved EF, high-energy phosphates were increased and lactic acid was decreased in the left ventricle (LV), with no changes in triglyceride or GLUT-4 levels.


CONCLUSIONS
Inhibiting MCD by an US-mediated injection of miRNA into the rat myocardium increased energy reserves in the LV after MI, most likely by limiting lactic acidosis and improving cardiac function without increasing lipid toxicity.
Department of Cardiology, Second Affiliated Hospital, Chongqing Medical University, Chongquing, PR China.
Hongquan
H
Wu
Que
Q
Zhu
Min
M
Cai
Xin
X
Tong
Dichuan
D
Liu
Jing
J
Huang
Gang
G
Yang
Yonghong
Y
Jiang
D000818:Animals; D001483:Base Sequence; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D057809:HEK293 Cells; D006333:Heart Failure / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D006334:Heart Function Tests; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000494:pharmacology / Q000627:therapeutic use*; D045423:Microbubbles; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010710:Phosphates / Q000378:metabolism; D010957:Plasmids; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D020257:Ventricular Remodeling / Q000187:drug effects*
D035683:MicroRNAs; D010710:Phosphates; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase