Gastrin exerts a protective effect against myocardial infarction via promoting angiogenesis

Abstract

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 (CCK2R) mediated the protective effect of gastrin since the CCK2R 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.

Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal Na + /H + Exchanger 3 Activity Through a PKC (Protein Kinase C)-Mediated NHERF1 and NHERF2 Pathway

“…There are beneficial effects of inhibition of intestinal NHE3 in addition to BP regulation and end-organ protection. 28,54 The long-term subcutaneous infusion of gastrin for 7 to 28 days protected against hypertensive nephropathy by normalizing BP, decreasing renal tubule cell apoptosis, and increasing macrophage efferocytosis 55 Gastrin treatment for 28 days also exerted a protective effect on myocardial infarction. 56 In our study, the high-salt dietmediated increase in renal injury was mitigated by gastrin-SiO 2 microspheres treatment for 7 weeks.…”

Correlation Study between Levels of Gastrin, Serum IGF-1, and GHBP and Growth and Development in Children with Short Stature Based on Big Data Analysis

“…3 Disease Markers IGF-1, a peptide and protein whose structure is similar to the insulin factor, is secreted by kidney, liver, and spleen cells. The growth hormone (GH)/IGF-1 axis, as a study hotspot in recent years, can regulate the bone balance in human body and determine the growth length, maturity of bone, and the obtained maximum bone mass before puberty [13], and its main manifestation is to maintain the bone mass at adult stage. IGF-1 can directly promote the cell differentiation and proliferation as a target cell, and GH can stimulate the IGF-1 produced by peripheral tissues especially liver.…”

Porous magnetic Silica nanoparticles loaded with sulforaphane mitigate myocardial infarction injury through upregulating HSP70

“…The MI mice were fed sotagli ozin for 4 weeks after LAD ligation to prevent ventricular arrhythmias [39].The MI mice were subcutaneously infused with gastrin for 28 day after LAD ligation to protect myocardium [40]. In the above pharmacological therapies, the drugs was administered after LAD ligation and need be continued for weeks to achieve therapeutic e cacy due to the mechanism of treatment, such as facilitating neovascularization [40]. However, the best time point to treat MI is in the early stages of infarction.…”

“…Due to the different pharmacological mechanisms of MI treatments, the drugs were administered before, or after ischemia. The studies reported that pharmacological therapy could be performed after LAD ligation in MI treatment [38][39][40], because there are still some lateral coronary arteries that could nourish the lesions of the heart in the MI animal model, except the occluded coronary artery. TH1834 was administered 3 days after LAD ligation and continued for 2 weeks, to speci cally inhibit the acetyltransferase and furtherly mitigate MI injury [38].…”

“…TH1834 was administered 3 days after LAD ligation and continued for 2 weeks, to speci cally inhibit the acetyltransferase and furtherly mitigate MI injury [38]. The MI mice were fed sotagli ozin for 4 weeks after LAD ligation to prevent ventricular arrhythmias [39].The MI mice were subcutaneously infused with gastrin for 28 day after LAD ligation to protect myocardium [40]. In the above pharmacological therapies, the drugs was administered after LAD ligation and need be continued for weeks to achieve therapeutic e cacy due to the mechanism of treatment, such as facilitating neovascularization [40].…”