Irisin Enhances Angiogenesis of Mesenchymal Stem Cells to Promote Cardiac Function in Myocardial Infarction via PI3k/Akt Activation

Abstract

Background and Objectives With the growing incidence of acute myocardial infarction (MI), angiogenesis is vital for cardiac function post-MI. The role of bone marrow mesenchymal stem cells (BMSCs) in angiogenesis has been previously confirmed. Irisin is considered a potential vector for angiogenesis. The objective of the present study was to investigate the potential role of irisin in the angiogenesis of BMSCs. Methods and Results In vivo , irisin-treated BMSCs (BMSCs＋irisin) were transplanted into an MI mouse model. On day 28 post-MI, blood vessel markers were detected, and cardiac function and infarct areas of mice were evaluated. In vitro , paracrine effects were assessed by examining tube formation in human umbilical vein endothelial cells (HUVECs) co-cultured with the BMSCs＋irisin supernatant. The scratch wound-healing assay was performed to evaluate HUVEC migration. Western blotting was performed to determine PI3k/Akt pathway activation in the BMSCs＋irisin group. Transplantation of BMSCs＋irisin promoted greater angiogenesis, resulting in better cardiac function in the MI mouse model than in controls. In the BMSC＋irisin group, HUVECs demonstrated enhanced tube formation and migration. Activation of the PI3k/Akt pathway was found to be involved in mediating the role of irisin in the angiogenesis of BMSCs. Conclusions In cardiovascular diseases such as MI, irisin administration can enhance angiogenesis of BMSCs and promote cardiac function via the PI3k/Akt pathway, optimizing the therapeutic effect based on BMSCs transplantation.

The emerging roles of irisin in vascular calcification

“…Besides, irisin inhibited endothelial cell senescence and G0/G1 phase cell cycle arrest through the p53/p21 pathway (102). Also, irisin might enhance the angiogenesis of mesenchymal stem cells and human umbilical vein endothelial cells (105,(114)(115)(116)(117). Therefore, irisin can protect vascular endothelium in multiple directions.…”

Serum Levels of Irisin Predict Cumulative Clinical Outcomes in Heart Failure Patients With Type 2 Diabetes Mellitus

“…Under physiological conditions, irisin appears to be a crucial element in adipose tissue browning, regulating glucose metabolism and influencing energy expenditure ( Moreno-Navarrete et al, 2013 ). Irisin has been found to have a tissue-protective effect on these target organs by promoting angiogenesis, reparation, vascular integrity, suppression of oxidative stress, fibrosis, reduction of cardiomyocyte apoptosis and ischemia/hypoxia-induced injury via the PI3k/Akt/mTOR and αV-integrin-induced extracellular signaling-related kinase/STAT pathways ( Liao et al, 2019 ; Yang et al, 2021 ). Unfortunately, there are contradictory findings regarding the role of irisin in HF patients.…”

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“…Their activation is related to excessive in ammatory response after pathogen invasion and plays a key role in the pathogenesis of sepsis. [14] According to the phenotypes and functions, macrophages can be divided into two types: M1 macrophages secrete a large number of pro-in ammatory cytokines; M2 macrophages release anti-in ammatory cytokines and have immunosuppressive repair function. [2,15] In the early stage of sepsis, macrophages are activated by bacteria to polarize M1 and release a large number of proin ammatory cytokines, such as TNF-a, IL-1b, IL-18, IL-6, IL-12, and HMGB1, cause a "cytokine storm".…”