title: Caffeic acid phenethyl ester possesses potent cardioprotective effects in a rabbit model of acute myocardial ischemia-reperfusion injury.
abstract: Although great achievements have been made in elucidating the molecular mechanisms contributing to acute myocardial ischemia/reperfusion (I/R) injury, an effective pharmacological therapy to protect cardiac tissues from serious damage associated with acute myocardial infarction, coronary arterial bypass grafting surgery, or acute coronary syndromes has not been developed. We examined the in vivo cardioprotective effects of caffeic acid phenethyl ester (CAPE), a natural product with potent anti-inflammatory, antitumor, and antioxidant activities. CAPE was systemically delivered to rabbits either 60 min before or 30 min after surgically inducing I/R injury. Infarct dimensions in the area at risk were reduced by >2-fold (P < 0.01) with CAPE treatment at either period. Accordingly, serum levels of normally cytosolic enzymes lactate dehydrogenase, creatine kinase (CK), MB isoenzyme of CK, and cardiac-specific troponin I were markedly reduced in both CAPE treatment groups (P < 0.05) compared with the vehicle-treated control group. CAPE-treated tissues displayed significantly less cell death (P < 0.05), which was in part due to inhibition of p38 mitogen-activated protein kinase activation and reduced DNA fragmentation often associated with caspase 3 activation (P < 0.05). In addition, CAPE directly blocked calcium-induced cytochrome c release from mitochondria. Finally, the levels of inflammatory proteins IL-1beta and TNF-alpha expressed in the area at risk were significantly reduced with CAPE treatment (P < 0.05). These data demonstrate that CAPE has potent cardioprotective effects against I/R injury, which are mediated, at least in part, by the inhibition of inflammatory and cell death responses. Importantly, protection is conferred when CAPE is systemically administered after the onset of ischemia, thus demonstrating potential efficacy in the clinical scenario.
authors.affiliation: Department of Pediatric Cardiology, AnZhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Jiangning
authors.initials: J
authors.lastname: Tan
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Ma
authors.forename: Ling
authors.initials: L
authors.lastname: Han
authors.forename: Ruyu
authors.initials: R
authors.lastname: Du
authors.forename: Liming
authors.initials: L
authors.lastname: Zhao
authors.forename: Xing
authors.initials: X
authors.lastname: Wei
authors.forename: Dongming
authors.initials: D
authors.lastname: Hou
authors.forename: Brian H
authors.initials: BH
authors.lastname: Johnstone
authors.forename: Martin R
authors.initials: MR
authors.lastname: Farlow
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Du
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002109:Caffeic Acids / Q000494:pharmacology*; D002316:Cardiotonic Agents; D020169:Caspases / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D007375:Interleukin-1 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D019210:Troponin I / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D002109:Caffeic Acids; D002316:Cardiotonic Agents; D007375:Interleukin-1; D019210:Troponin I; D014409:Tumor Necrosis Factor-alpha; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; D048051:p38 Mitogen-Activated Protein Kinases; D003402:Creatine Kinase; D020169:Caspases; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol