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一种新型小分子化合物 VCP979 可改善心肌缺血/再灌注损伤小鼠模型的心室重构。

A novel small molecule compound VCP979 improves ventricular remodeling in murine models of myocardial ischemia/reperfusion injury.

机构信息

Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.

Research Center for Translational Medicine, Shanghai 200120, P.R. China.

出版信息

Int J Mol Med. 2020 Feb;45(2):353-364. doi: 10.3892/ijmm.2019.4413. Epub 2019 Nov 27.

DOI:10.3892/ijmm.2019.4413
PMID:31789413
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6984775/
Abstract

Persistent ventricular remodeling following myocardial ischemia/reperfusion (MI/R) injury results in functional decompensation and eventual progression to heart failure. VCP979, a novel small‑molecule compound developed in‑house, possesses anti‑inflammatory and anti‑fibrotic activities. In the present study, no significant pathological effect was observed following the administration of VCP979 on multiple organs in mice and no difference of aspartate transaminase/alanine aminotransferase/lactate dehydrogenase levels was found in murine serum. Treatment with VCP979 ameliorated cardiac dysfunction, pathological myocardial fibrosis and hypertrophy in murine MI/R injury models. The administration of VCP979 also inhibited the infiltration of inflammatory cells and the pro‑inflammatory cytokine expression in hearts post MI/R injury. Further results revealed that the addition of VCP979 prevented the primary neonatal cardiac fibroblasts (NCFs) from Angiotensin II (Ang II)‑induced collagen synthesis and neonatal cardiac myocytes (NCMs) hypertrophy. In addition, VCP979 attenuated the activation of p38‑mitogen‑activated protein kinase in both Ang II‑induced NCFs and hearts subjected to MI/R injury. These findings indicated that the novel small‑molecule compound VCP979 can improve ventricular remodeling in murine hearts against MI/R injury, suggesting its potential therapeutic function in patients subjected to MI/R injury.

摘要

心肌缺血/再灌注（MI/R）损伤后持续性心室重构导致功能失代偿，最终进展为心力衰竭。VCP979 是一种新型的小分子化合物，由本公司开发，具有抗炎和抗纤维化作用。在本研究中，VCP979 在小鼠的多个器官上给药后未观察到明显的病理效应，并且在小鼠血清中未发现天冬氨酸转氨酶/丙氨酸转氨酶/乳酸脱氢酶水平的差异。VCP979 治疗改善了 MI/R 损伤小鼠的心脏功能障碍、病理性心肌纤维化和肥大。VCP979 的给药还抑制了 MI/R 损伤后心脏中炎症细胞的浸润和促炎细胞因子的表达。进一步的结果表明，添加 VCP979 可防止原代乳鼠心肌成纤维细胞（NCFs）被血管紧张素 II（Ang II）诱导的胶原合成和乳鼠心肌细胞（NCMs）肥大。此外，VCP979 减弱了 Ang II 诱导的 NCFs 和 MI/R 损伤心脏中 p38-丝裂原活化蛋白激酶的激活。这些发现表明，新型小分子化合物 VCP979 可改善 MI/R 损伤小鼠心脏的心室重构，提示其在 MI/R 损伤患者中的潜在治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/441f/6984775/a4a36de4e5e2/IJMM-45-02-0353-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/441f/6984775/9bf85bd4eed3/IJMM-45-02-0353-g00.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/441f/6984775/94a904c6021b/IJMM-45-02-0353-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/441f/6984775/a4a36de4e5e2/IJMM-45-02-0353-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/441f/6984775/9bf85bd4eed3/IJMM-45-02-0353-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/441f/6984775/92ea860b8662/IJMM-45-02-0353-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/441f/6984775/4330a191f42b/IJMM-45-02-0353-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/441f/6984775/a75d09cc7805/IJMM-45-02-0353-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/441f/6984775/f8b2c10a2a50/IJMM-45-02-0353-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/441f/6984775/94a904c6021b/IJMM-45-02-0353-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/441f/6984775/a4a36de4e5e2/IJMM-45-02-0353-g06.jpg

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