Overexpression of integrin-linked kinase improves cardiac function in a rat model of doxorubicin induced chronic heart failure
10.3760/cma.j.issn.0253-3758.2014.03.010
- VernacularTitle:过表达整合素连接激酶可改善慢性心力衰竭大鼠心功能
- Author:
Jian BAI
1
;
Rong GU
;
Bingjian WANG
;
Na ZHANG
;
Lina KANG
;
Biao XU
Author Information
1. 210008,南京大学医学院附属鼓楼医院心内科
- Keywords:
Heart failure,congestive;
Cell proliferation;
Apoptosis;
Integrin-linked kinase
- From:
Chinese Journal of Cardiology
2014;42(3):225-229
- CountryChina
- Language:Chinese
-
Abstract:
Objective The aim of this study is to investigate the effects of cardiac integrin-linked kinase (ILK) overexpression in a rat model of doxorubicin-induced heart failure and the underlying mechanisms.Methods Rat heart failure model was induced by intraperitoneal administration of doxorubicin (6 injections within 2 weeks: total dose =15 mg/kg).Five weeks after the first injection,rats with heart failure were confirmed by echocardiography and then randomly divided into Ad-ILK group (intramyocardially injected with adenoviral vector expressing ILK) and Ad-null group (intramyocardially injected with empty ad-null,n =20 each).After 4 weeks,ILK expression and activity were detected by Western blot,cardiac function was determined by echocardiographic and hemodynamic examinations.Apoptosis was measured by TUNEL analysis and cardiomyocyte proliferation was estimated by phosphohistone-H3 staining.Results Western blot analysis revealed higher expression of ILK as well as the phosphorylation levels of Akt in AdILK hearts as compared with ad-null controls.Four weeks after transfection,LVEF and LVFS were significantly higher in Ad-ILK group as compared with control group [LVEF: (60.56 ± 2.61)％ vs.(51.94±2.28)％,P＜0.05; LVFS: (28.10± 1.83)％ vs.(22.82 ± 1.68)％,P ＜0.05].The LVEDD and LVESD,as well as LVEDP were significantly lower in Ad-ILK group compared with control group [LVEDD: (6.22 ± 0.24) mm vs.(7.15 ± 0.21) mm,P ＜ 0.05 ; LVESD: (4.42 ± 0.23) mm vs.(5.65±0.25) mm,P＜0.05; LVEDP: (12.96±2.10) mmHgvs.(21.45±2.48) mmHg(1 mmHg=0.133 kPa),P ＜0.05].Reduced levels of serum BNP was also seen in the Ad-ILK group.TUNEL analysis showed that ILK treatment significantly inhibited the apoptosis of cardiomyocytes [(0.23 ± 0.02) ％ vs.(0.45 ± 0.04)％,P ＜ 0.05].Moreover,increased cardiomyocyte proliferation was found in Ad-ILK group through the phospho-histone H3 staining [(0.60 ± 0.07) ％ vs.(0.24 ± 0.03) ％,P ＜ 0.01].Conclusion ILK gene therapy improves cardiac function in this rat model of heart failure,and is associated with reduced apoptosis and increased cardiomyocyte proliferation.
