Abstract
Although it is known that caffeic acid phenethyl ester (CAPE) and its derivatives could ameliorate acute myocardial injury, their effects on chronic myocardial ischemia (CMI) were not reported. This study aimed to investigate the potential effect of caffeic acid p-nitro phenethyl ester (CAPE-pNO2, a derivative of CAPE) on CMI and underlying mechanisms. SD rats were subjected to high-fat-cholesterol-diet (HFCD) and vitamin D3, and the H9c2 cells were treated with LPS to establish CMI model, followed by the respective treatment with saline, CAPE, or CAPE-pNO2. In vivo, CAPE-pNO2 could reduce serum lipid levels and improve impaired cardiac function and morphological changes. Data of related assays indicated that CAPE-pNO2 downregulated the expression of transforming growth factor-β1 (TGF-β1) and galectin-3 (Gal-3). Besides, CAPE-pNO2 decreased collagen deposition, the number of apoptotic cardiomyocytes, and some related downstream proteins of Gal-3 in the CMI rats. Interestingly, the effects of CAPE-pNO2 on TGF-β1, Gal-3, and other proteins expressed in the lung were consistent with that in the heart. In vitro, CAPE-pNO2 could attenuate the fibrosis, apoptosis, and inflammation by activating TGF-β1/Gal-3 pathway in LPS-induced H9c2 cell. However, CAPE-pNO2-mediated cardioprotection can be eliminated when treated with modified citrus pectin (MCP, an inhibitor of Gal-3). And in comparison, CAPE-pNO2 presented stronger effects than CAPE. This study indicates that CAPE-pNO2 may ameliorate CMI by suppressing fibrosis, inflammation, and apoptosis via the TGF-β1/Gal-3 pathway in vivo and in vitro.
Highlights
Myocardial ischemia (MI) refers to a pathological state of decreased blood perfusion of heart, which results in aberrant vascular regeneration in ischemic areas, fibrosis, oxidative stress, inflammation and even cardiovascular dysfunction [1, 2], and its common cause is coronary atherosclerosis [3]
Data of related assays indicated that caffeic acid phenethyl ester (CAPE)-pNO2 down-regulated the expression of transforming growth factor-β1 (TGF-β1) and galectin-3 (Gal-3)
This study indicates that CAPE-pNO2 may ameliorate chronic myocardial ischemia (CMI) by suppressing fibrosis, inflammation and apoptosis via the TGF-β1/Gal-3 pathway in vivo and in vitro
Summary
Myocardial ischemia (MI) refers to a pathological state of decreased blood perfusion of heart, which results in aberrant vascular regeneration in ischemic areas, fibrosis, oxidative stress, inflammation and even cardiovascular dysfunction [1, 2], and its common cause is coronary atherosclerosis [3]. Transforming growth factor-β1 (TGF-β1) plays a role in cardiac remodeling and affects cell apoptosis, fibrosis and hypertrophy, which aggravates myocardial ischemia/reperfusion injury (MIRI) [5]. Experiments have confirmed that the down-regulated TGF-β1 has protective effects on myocardial apoptosis and MIRI. Notoginsenoside R1 and mangiferin preconditioning could protect the heart from ischemia reperfusion-induced myocardial injury by inhibiting activation of TGF-β1-TAK1 signaling pathway [6, 7]. It is known that caffeic acid phenethyl ester (CAPE) and its derivatives could ameliorate acute myocardial injury, their effects on chronic myocardial ischemia (CMI) were not reported. This study aimed to investigate the potential effect of caffeic acid p-nitro phenethyl ester (CAPE-pNO2, a derivative of CAPE) on CMI and underlying mechanisms
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