Abstract
BackgroundIt 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.MethodsAdult 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.ResultsWe 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 (CCK2R) mediated the protective effect of gastrin since the CCK2R blocker CI988 attenuated the gastrin-mediated angiogenesis and cardiac function protection.ConclusionOur data revealed that gastrin promoted angiogenesis and improved cardiac function in post-MI mice, highlighting its potential as a therapeutic target candidate.
Highlights
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)
Gastrin improves cardiac function and survival rate in post‐MI mice Ventricular function was evaluated in all groups to assess the gastrin effects on cardiac hemodynamics
Our results suggested that compared with sham-operated mice, post-MI mice had increased ventricular dilation and decreased cardiac function
Summary
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). Clinical data revealed that serum gastrin levels were increased in patients with MI (Lapidus 1985; Tansey et al 1981) and were associated with lower serum levels of cardiac troponin I in patients with unstable angina pectoris undergoing PCI (Yang et al 2018). It is not clear if the increase in serum gastrin level is the result of MI or an attempt of the body to protect itself against cardiomyocyte damage after MI occurred. It is possible that gastrin may exert a protective effect against myocardial infarction
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