Chlorogenic Acid Attenuates Ventricular Remodeling After Myocardial Infarction in Mice

Abstract

SummaryChlorogenic acid (CGA), which is a key component of coffee, has many biological effects such as anti-inflammation activity. However, the effects of CGA on ventricular remodeling after myocardial ischemia have not been well investigated. To test the hypothesis that CGA can attenuate chronic ventricular remodeling after myocardial ischemia, we orally administered CGA to murine myocardial ischemia models. Seven to nine week-old C57BL/6 mice were used. A myocardial infarction (MI) model was produced by permanent ligation of the left anterior descending coronary artery (LAD) using an 8-0 suture passed under the arteries. These mice were randomly assigned into 4 groups in each experimental model. Some MI mice were supplemented orally with CGA (30 mg/kg/day, MI+CGA group, n = 13) as a CGAtreated MI group, and other MI mice received vehicle (MI+vehicle group, n = 11) as a vehicle-treated MI group. Shamoperated mice without MI also received vehicle (Sham+vehicle group, n = 3) as a sham group, and sham-operated mice without MI received CGA (30 mg/kg/day, Sham+CGA group, n = 8) as a Sham+CGA group. Just before sacrifice on day 14, we measured blood pressure and heart rate and performed echocardiography. We obtained 3 transverse sections per heart for histopathologic examination. There were no differences in body weight, heart rate, or blood pressure among the groups on day 14. The vehicle-treated MI group showed significantly impaired left ventricular contraction compared to the sham-operated group. However, the CGA-treated MI group showed significantly improved ventricular contraction compared to the vehicle-treated MI group. Severe myocardial fibrosis with enhanced macrophage infiltration was observed in the vehicle-treated ischemia group on day 14. CGA attenuated these fibrotic changes with suppressed macrophage infiltration without systemic adverse effects. CGA may effectively suppress chronic ventricular remodeling after myocardial ischemia because it is critically involved in the suppression of macrophage infiltration. (Int Heart J 2013; 54: 176-180) Key words: Myocardial Ischemia, Coffee, Polyphenols, Inflammation, Cytokine T he mortality rate in patients with coronary arterial disease (CAD), including myocardial infarction (MI), is high. 1) Myocardial necrosis and ventricular remodeling after MI lead to arrhythmia, cardiac rupture, and heart failure. These complications often result in death. Many studies have shown that macrophage related inflammatory responses are increased by myocardial necrosis.2,3) These inflammatory responses lead to an increase in fibroblasts and increased collagen synthesis. 4-7)Chlorogenic acid (8-tetrahydroxycyclohexacarboxylic acid, 3-(3,4-dihydroxycinnamate, CGA) is a key component of coffee. 8,9) It is known that CGA has many biological effects, such as anti-inflammation, antioxidation, and antihypertension effects.10) It has been reported that CGA could suppress inflammatory factors and attenuate remodeling of liver ischemic injury in mice.11) Although they are well documented,...

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