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Protection of CAPE-pNO2 Against Chronic Myocardial Ischemia by the TGF-Β1/Galectin-3 Pathway In Vivo and In Vitro

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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.

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Data Availability

Data supporting the results of this research are available to the corresponding author on request.

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Funding

This work was financially supported by the Fundamental research funds for the central university, China (SWU021003), Shanxi Zhaoyi Biological Co. Ltd., China (SWU2013130), and Skagen Animal Health Products (Shangqiu) Co., Ltd., China (2021073).

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  1. Qin Wan and Liwen Zhang share authorship.

Authors and Affiliations

  1. College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China

    Qin Wan, Liwen Zhang, Qidi Zhou, Yanmin Han, Zhubo Li & Boheng Li

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  1. Qin Wan
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  2. Liwen Zhang
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  3. Qidi Zhou
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  4. Yanmin Han
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Contributions

Li Z, Zhang L, and Li B designed the project; Zhang L, Wan Q, and Han Y performed the experiments; Zhang L, Wan Q, Li Z, Li B, and Zhou Q wrote the manuscripts; Zhang L analyzed and interpreted data; and all authors reviewed the manuscript.

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Correspondence to Zhubo Li or Boheng Li.

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All the animal protocols were consistent with the National Institutes of Health (NIH) guidelines and approved by the Ethical Committee for Animals of Southwest University.

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Wan, Q., Zhang, L., Zhou, Q. et al. Protection of CAPE-pNO2 Against Chronic Myocardial Ischemia by the TGF-Β1/Galectin-3 Pathway In Vivo and In Vitro. Inflammation 45, 1039–1058 (2022). https://doi.org/10.1007/s10753-021-01600-1

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