4.7 Article

Chinese medicine Fufang Zhenzhu Tiaozhi capsule ameliorates coronary atherosclerosis in diabetes mellitus-related coronary heart disease minipigs

Journal

BIOMEDICINE & PHARMACOTHERAPY
Volume 156, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2022.113831

Keywords

Coronary atherosclerosis; Chinese medicine; Inflammation; Apoptosis; Endothelial-mesenchymal transition

Funding

  1. National Key Research and Development Program of China [2018YFC1704200]
  2. Major Basic and Applied Basic Research Projects of Guangdong Province of China [2019B030302005]
  3. Key Project of the National Natural Science Foundation of China [81530102]
  4. Basic and Applied Basic Research Project of Guangdong Province of China [2018A030313391, 2019A1515110123, 2020A1515010155, 2021A1515012553]
  5. Innovation and Strengthening University Project Subsidized Project of Guangdong Pharmaceutical University [2018KTSCX112]

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The study aims to investigate the unique mechanism of FTZ in the treatment of DM-CHD minipigs with coronary atherosclerosis. The results showed that FTZ significantly improved disordered glycolipid metabolism, reduced coronary stenosis and myocardial injury in DM-CHD minipigs. FTZ also reversed the abnormal protein expressions in the DM-CHD coronary artery and ameliorated the damage and high migration activity of HUVECs induced by high glucose.
Background: Diabetes mellitus-related coronary heart disease (DM-CHD) is the most common cause of death in diabetic patients. Various studies have shown that Chinese medicine Fufang-Zhenzhu-Tiaozhi capsule (FTZ) has therapeutic effects on cardiovascular diseases. More research is required to determine the mechanism of FTZ protection against coronary atherosclerosis.Objective: To investigate the unique mechanism of FTZ in treatment of DM-CHD minipigs with coronary atherosclerosis.Methods: High-fat/high-sucrose/high-cholesterol diet combined with streptozotocin and coronary balloon injury were used to induce DM-CHD minipig model, which was then randomly divided into: DM-CHD model, DM-CHD treated with FTZ or positive drug (Metformin + Atorvastatin, M+A). After twenty-two weeks, ultrasonography, electrocardiography, and image detection were employed to detect cardiac functions and assess coronary artery stenosis and plaque. Human umbilical vein endothelial cells (HUVECs) were treated high glucose or/and FTZ. Pigs tissues and treated-cells were collected for further testing.Results: In DM-CHD minipigs, FTZ treatment significantly reduced disordered glycolipid metabolism similar as M+A administration. FTZ and M+A also alleviated coronary stenosis and myocardial injury. In addition, I Kappa B and NF-Kappa B phosphorylation levels, as well as the protein levels of IL-1 beta, Bax, cleave-Caspase 3, Bcl-2, and alpha-SMA were dramatically increased in the DM-CHD coronary artery, whereas CD31 and VE-cadherin expressions were decreased. Similar to M+A, FTZ reversed these protein levels in the DM-CHD coronary artery. Furthermore, FTZ ameliorated the damage and high migration activity of HUVECs induced by high glucose.

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