EP 80317, a selective CD36 ligand, shows cardioprotective effects against post-ischaemic myocardial damage in mice.
OBJECTIVE
The CD36 receptor plays an important role in facilitating fatty acid transport to the heart. The present study aimed to assess whether EP 80317, a selective synthetic peptide ligand of CD36, is cardioprotective in a murine model of myocardial ischaemia and reperfusion (MI/R) injury.


RESULTS
Mice were pretreated with daily subcutaneous injections of EP 80317 for 14 days before being subjected to a 30 min ligation of the left anterior descending coronary artery. The treatment reduced the infarct area and improved myocardial haemodynamics and function, as shown by an increase in cardiac output, ejection fraction and stroke work, and a reduced total peripheral resistance. In contrast, administration of EP 51389, a tripeptide analogue devoid of binding affinity to CD36, did not protect against myocardial injury. Six hours after myocardial reperfusion, EP 80317-treated mice showed reduced myocardial fatty acid uptake, as assessed by micro-positron emission tomography, in agreement with reduced levels of circulating non-esterified fatty acids. Studies using [(14)C]-palmitate infusion revealed reduced lipolysis, although no significant change in insulin or catecholamine plasma levels were observed. Increased expression levels of adipogenic and anti-lipolytic genes further supported an effect of EP 80317 in preventing fatty acid mobilization from adipose tissue. No effect of the treatment was observed in CD36(-/-) mice.


CONCLUSIONS
Our results show that pretreatment with EP 80317 protected the heart against damage and dysfunction elicited by MI/R, along with a transient reduction in peripheral lipolysis. Our findings support CD36 as a novel target for the treatment of ischaemic cardiopathy.
Faculty of Pharmacy,  Université de Montréal, PO Box 6128, Station Centre-Ville, Montréal, Québec,  Canada H3C 3J7.
Valérie L
VL
Bessi
Sébastien M
SM
Labbé
David N
DN
Huynh
Liliane
L
Ménard
Christian
C
Jossart
Maria
M
Febbraio
Brigitte
B
Guérin
M'Hamed
M
Bentourkia
Roger
R
Lecomte
André C
AC
Carpentier
Huy
H
Ong
Sylvie
S
Marleau
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D018955:CD36 Antigens / Q000737:chemistry; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D004734:Energy Metabolism / Q000187:drug effects; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D019788:Fluorodeoxyglucose F18; D008297:Male; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging / Q000378:metabolism / Q000517:prevention & control*; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019275:Radiopharmaceuticals; D016277:Ventricular Function, Left / Q000187:drug effects
D018955:CD36 Antigens; D002316:Cardiotonic Agents; C468852:EP80317; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D009842:Oligopeptides; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C071178:14-fluoro-6-thiaheptadecanoic acid; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases