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Gastrin exerts a protective effect against myocardial infarction via promoting angiogenesis

BACKGROUND: It is known that increased gastrin concentration is negatively correlated with cardiovascular mortality, and plasma gastrin levels are increased in patients after myocardial infarction (MI). However, whether gastrin can play a protective role in MI remains unknown. METHODS: Adult C57BL/6...

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Autores principales: Fu, Jinjuan, Tang, Yuanjuan, Zhang, Zhen, Tong, Lin, Yue, Rongchuan, Cai, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375043/
https://www.ncbi.nlm.nih.gov/pubmed/34412590
http://dx.doi.org/10.1186/s10020-021-00352-w
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author Fu, Jinjuan
Tang, Yuanjuan
Zhang, Zhen
Tong, Lin
Yue, Rongchuan
Cai, Lin
author_facet Fu, Jinjuan
Tang, Yuanjuan
Zhang, Zhen
Tong, Lin
Yue, Rongchuan
Cai, Lin
author_sort Fu, Jinjuan
collection PubMed
description BACKGROUND: It is known that increased gastrin concentration is negatively correlated with cardiovascular mortality, and plasma gastrin levels are increased in patients after myocardial infarction (MI). However, whether gastrin can play a protective role in MI remains unknown. METHODS: Adult C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery (LAD) and subcutaneous infusion of gastrin (120 μg/Kg body weight/day, 100 μL in the pump) for 28 days after MI. Plasma gastrin concentrations were measured through an ELISA detection kit. Mice were analyzed by echocardiography after surgery. CD31 and VEGF expression were quantified using immunofluorescence staining or/and western blot to assess the angiogenesis in peri-infarct myocardium. Capillary-like tube formation and cell migration assays were performed to detect gastrin-induced angiogenesis. RESULTS: We found that gastrin administration significantly ameliorated MI-induced cardiac dysfunction and reduced fibrosis at 28 days in post-MI hearts. Additionally, gastrin treatment significantly decreased cardiomyocyte apoptosis and increased angiogenesis in the infarct border zone without influencing cardiomyocyte proliferation. In vitro results revealed that gastrin up-regulated the PI3K/Akt/vascular endothelial growth factor (VEGF) signaling pathway and promoted migration and tube formation of human coronary artery endothelial cells (HCAECs). Cholecystokinin 2 receptor (CCK(2)R) mediated the protective effect of gastrin since the CCK(2)R blocker CI988 attenuated the gastrin-mediated angiogenesis and cardiac function protection. CONCLUSION: Our data revealed that gastrin promoted angiogenesis and improved cardiac function in post-MI mice, highlighting its potential as a therapeutic target candidate.
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spelling pubmed-83750432021-08-19 Gastrin exerts a protective effect against myocardial infarction via promoting angiogenesis Fu, Jinjuan Tang, Yuanjuan Zhang, Zhen Tong, Lin Yue, Rongchuan Cai, Lin Mol Med Research Article BACKGROUND: It is known that increased gastrin concentration is negatively correlated with cardiovascular mortality, and plasma gastrin levels are increased in patients after myocardial infarction (MI). However, whether gastrin can play a protective role in MI remains unknown. METHODS: Adult C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery (LAD) and subcutaneous infusion of gastrin (120 μg/Kg body weight/day, 100 μL in the pump) for 28 days after MI. Plasma gastrin concentrations were measured through an ELISA detection kit. Mice were analyzed by echocardiography after surgery. CD31 and VEGF expression were quantified using immunofluorescence staining or/and western blot to assess the angiogenesis in peri-infarct myocardium. Capillary-like tube formation and cell migration assays were performed to detect gastrin-induced angiogenesis. RESULTS: We found that gastrin administration significantly ameliorated MI-induced cardiac dysfunction and reduced fibrosis at 28 days in post-MI hearts. Additionally, gastrin treatment significantly decreased cardiomyocyte apoptosis and increased angiogenesis in the infarct border zone without influencing cardiomyocyte proliferation. In vitro results revealed that gastrin up-regulated the PI3K/Akt/vascular endothelial growth factor (VEGF) signaling pathway and promoted migration and tube formation of human coronary artery endothelial cells (HCAECs). Cholecystokinin 2 receptor (CCK(2)R) mediated the protective effect of gastrin since the CCK(2)R blocker CI988 attenuated the gastrin-mediated angiogenesis and cardiac function protection. CONCLUSION: Our data revealed that gastrin promoted angiogenesis and improved cardiac function in post-MI mice, highlighting its potential as a therapeutic target candidate. BioMed Central 2021-08-19 /pmc/articles/PMC8375043/ /pubmed/34412590 http://dx.doi.org/10.1186/s10020-021-00352-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Fu, Jinjuan
Tang, Yuanjuan
Zhang, Zhen
Tong, Lin
Yue, Rongchuan
Cai, Lin
Gastrin exerts a protective effect against myocardial infarction via promoting angiogenesis
title Gastrin exerts a protective effect against myocardial infarction via promoting angiogenesis
title_full Gastrin exerts a protective effect against myocardial infarction via promoting angiogenesis
title_fullStr Gastrin exerts a protective effect against myocardial infarction via promoting angiogenesis
title_full_unstemmed Gastrin exerts a protective effect against myocardial infarction via promoting angiogenesis
title_short Gastrin exerts a protective effect against myocardial infarction via promoting angiogenesis
title_sort gastrin exerts a protective effect against myocardial infarction via promoting angiogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375043/
https://www.ncbi.nlm.nih.gov/pubmed/34412590
http://dx.doi.org/10.1186/s10020-021-00352-w
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