Effect of transplantation of cardiac stem cells overexpressing integrin‑linked kinase on cardiac function of rats with acute myocardial infarction

Abstract

In the present study, we aimed to investigate the effect of transplantation of cardiac stem cells (CSCs) overexpressing integrin-linked kinase (ILK) on cardiac function of rats with acute myocardial infarction (MI). A total of 60 rats were randomly divided into normal saline (NS) group (n=20), green fluorescent protein (GFP)-CSC group (n=20) and ILK-CSC group (n=20). In the ILK-CSC group, CSCs in rats were transfected with GFP adenovirus vector overexpressing ILK. The rat model of MI was established. The cardiac function 4 weeks after transplantation was detected via echocardiography, and the exhaustive swimming experiment was performed to observe the exercise load capacity. Moreover, Ki-67 and P-H3 proteins in myocardial tissues of rats were detected via immunohistochemistry, and the expression of GFP was observed under a fluorescence microscope. Cells in the GFP-CSC group were transfected with the empty GFP adenovirus, while those in NS group were not transfected, and other treatments in these two groups were the same as those in the ILK-CSC group. Four weeks after transplantation, left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) of rats in the ILK-CSC group were smaller than those in the GFP-CSC group, but left ventricular ejection fraction (LVEF) (69.88±5.61 mm) was higher than that in the GFP-CSC group (P<0.05). The exercise time in the ILK-CSC group (12.69±0.58 min) was longer than that in the GFP-CSC and NS groups (P<0.05). The expression levels of Ki-67 and P-H3 proteins in myocardial cells of rats in the ILK-CSC group were higher than those in the GFP-CSC and NS groups (P<0.05). The number of transplanted cells retained around the infarct region in the ILK-CSC group 3 days after transplantation was obviously larger than that in the GFP-CSC group (P<0.001). Intramyocardial injection of CSCs overexpressing ILK immediately after the establishment of rat model of MI can promote myocardial cell proliferation, improve cardiac function and increase exercise capacity of rats.

Therapeutic effect of integrin-linked kinase gene-modified bone marrow-derived mesenchymal stem cells for streptozotocin-induced diabetic cystopathy in a rat model

“…Meanwhile, ILK can act as a pro-survival factor and play a role in protecting cells from high glucose-associated apoptosis and oxidative stress [ 24 , 25 ]. Overexpression of ILK can promote proliferation and vascular differentiation of stem cells and improve muscular function [ 26 ]. We have previously found that overexpression of ILK enhances the regeneration of native smooth muscle cells and improves muscle contractile function [ 27 ].…”

Endothelial ILK induces cardioprotection by preventing coronary microvascular dysfunction and endothelial-to-mesenchymal transition

“…Of note, our mice model exhibited normal levels of myocardial ILK expression. In addition, a number of preclinical studies reported the effect of ILK-MSCs on myocardial infarction using mouse, rat and porcine animal models, which evidenced a sizable reduction in infarct size and fibrosis, and significant improvement in regional perfusion and vessel density when compared with vector-MSCs [ 28 , 30 , 56 ]. It is possible to speculate that ILK-MSC used in preclinical models to reduce infarct size may also differentiate into ECs, restoring ILK levels in coronary endothelium.…”

“…Integrin Linked Kinase (ILK) is a serine/threonine kinase that binds to the cytoplasmic domain of β-integrins and participates in cardiac remodelling after MI [ 30 , 56 ]. ILK lies upstream of many intracellular signalling pathways potentially involved in such effect, including angiogenesis, mechanotransduction, extracellular matrix-mediated signalling, cell survival, proliferation, differentiation and apoptosis [ 26 , 29 ].…”

A Potential Role for Integrin-Linked Kinase in Colorectal Cancer Growth and Progression via Regulating Senescence and Immunity

“…ILK inhibition attenuated the induced hypertrophy ( Lu et al, 2006 ). In contrast, ILK overexpression has been implicated in myocardial infraction, a disease that leads to heart failure resulted from myocardial cell death ( Zhang and Guo, 2018 ). Transplanting cardiac stem cells overexpressing ILK restores cell death and cardiac function in a mouse model of this disease ( Zhang and Guo, 2018 ).…”

“…In contrast, ILK overexpression has been implicated in myocardial infraction, a disease that leads to heart failure resulted from myocardial cell death ( Zhang and Guo, 2018 ). Transplanting cardiac stem cells overexpressing ILK restores cell death and cardiac function in a mouse model of this disease ( Zhang and Guo, 2018 ). Furthermore, the mouse Alzheimer’s disease model displays a decrease in ILK expression, whereas its overexpression rescues hippocampal neurogenesis and defects in memory via the downstream signaling pathway, Akt/GSK3β ( Xu X.F.…”