Caffeic acid phenethyl ester possesses potent cardioprotective effects in a rabbit model of acute myocardial ischemia-reperfusion injury

Jiangning Tan, Zhizhong Ma, Ling Han, Ruyu Du, Liming Zhao, Xing Wei, Dongming Hou, Brian H. Johnstone, Martin Farlow, Yansheng Du

Research output: Contribution to journalArticle

35 Citations (Scopus)

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-1β and TNF-α 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.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number5 58-5
DOIs
StatePublished - Nov 2005

Fingerprint

Myocardial Reperfusion Injury
Reperfusion Injury
Myocardial Ischemia
Rabbits
Cell Death
caffeic acid phenethyl ester
MB Form Creatine Kinase
Troponin I
p38 Mitogen-Activated Protein Kinases
DNA Fragmentation
Acute Coronary Syndrome
Creatine Kinase
Cytochromes c
Biological Products
Interleukin-1
L-Lactate Dehydrogenase
Caspase 3
Isoenzymes
Mitochondria
Anti-Inflammatory Agents

Keywords

  • Apoptosis
  • Caspase 3
  • p38 mitogen-activated protein kinase
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology

Cite this

Caffeic acid phenethyl ester possesses potent cardioprotective effects in a rabbit model of acute myocardial ischemia-reperfusion injury. / Tan, Jiangning; Ma, Zhizhong; Han, Ling; Du, Ruyu; Zhao, Liming; Wei, Xing; Hou, Dongming; Johnstone, Brian H.; Farlow, Martin; Du, Yansheng.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 289, No. 5 58-5, 11.2005.

Research output: Contribution to journalArticle

Tan, Jiangning ; Ma, Zhizhong ; Han, Ling ; Du, Ruyu ; Zhao, Liming ; Wei, Xing ; Hou, Dongming ; Johnstone, Brian H. ; Farlow, Martin ; Du, Yansheng. / Caffeic acid phenethyl ester possesses potent cardioprotective effects in a rabbit model of acute myocardial ischemia-reperfusion injury. In: American Journal of Physiology - Heart and Circulatory Physiology. 2005 ; Vol. 289, No. 5 58-5.
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AU - Tan, Jiangning

AU - Ma, Zhizhong

AU - Han, Ling

AU - Du, Ruyu

AU - Zhao, Liming

AU - Wei, Xing

AU - Hou, Dongming

AU - Johnstone, Brian H.

AU - Farlow, Martin

AU - Du, Yansheng

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AB - 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-1β and TNF-α 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.

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