title: Mesenchymal stem cells overexpressing integrin-linked kinase attenuate left ventricular remodeling and improve cardiac function after myocardial infarction.
abstract: In the present study, we investigated whether mesenchymal stem cells (MSCs) overexpressing integrin-linked kinase (ILK) might regulate ventricular remodeling and cardiac function in a porcine myocardial infarction model. ILK-modified MSCs (ILK-MSCs) (n = 8), MSCs (n = 8) or placebo (n = 8) were injected into peri-infarct myocardium 7 days after ligation of the left anterior descending coronary artery. ILK expression was confirmed by immunofluorescence, real-time PCR, Western blot analysis, and flow cytometry. In vitro assays indicated increased proliferation and reduced apoptosis of MSCs due to overexpression of ILK. Echocardiographic, single-photon emission computed tomography and positron emission tomography analyses demonstrated preserved cardiac function and myocardial perfusion. Reduced fibrosis, increased cardiomyocyte proliferation, and enhanced angiogenesis were observed in the ILK-MSC group. Reduced apoptosis, as demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling analysis, was also noted. In conclusion, ILK promotes MSC proliferation and suppresses apoptosis. ILK-MSC transplantation improves ventricular remodeling and cardiac function in pigs after MI. It is associated with increased angiogenesis, reduced apoptosis, and increased cardiomyocyte proliferation. This may represent a new approach to the treatment of post-infarct remodeling and subsequent heart failure.
authors.affiliation: Department of Cardiology, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Suzhou University, Changzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Mao
authors.forename: Chengxi
authors.initials: C
authors.lastname: Lin
authors.forename: Jianshu
authors.initials: J
authors.lastname: Gao
authors.forename: Xiulin
authors.initials: X
authors.lastname: Liang
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.forename: Lina
authors.initials: L
authors.lastname: Kang
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000201:enzymology*; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D013552:Swine; D013556:Swine, Miniature; D020257:Ventricular Remodeling; D000099200:Scaffold Protein ILK
chemical_list: D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK