Association between lososomal cysteine protease cathepsin's activation and left ventricular function and remodeling in hypertensive heart failure rats
10.3321/j.issn:0253-3758.2008.01.013
- VernacularTitle:高血压性心脏病左心室重构进展中的组织蛋白酶S基因表达及其活性变化的临床意义
- Author:
Xian-Wu CHENG
1
;
Jie ZHANG
;
Hui SONG
;
Guang YANG
;
Xiao-Zhi QIN
;
Li-Ke GUAN
;
Hai JIN
;
Okumura KENJI
;
Murohara TOYOAKI
Author Information
1. 日本名古屋大学医学部
- Keywords:
Hypertension;
Cathepsins;
Ventricular remodeling
- From:
Chinese Journal of Cardiology
2008;36(1):51-56
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe myocardial cathepsin (Cat) S expression and activity in hypertensive heart failure rats.Methods The expression and activity of Cat S were determined in the left ventricular (LV) myocardium (LVM) of Dahl salt-sensitive rats fed either a high-salt(HS,8%)or low-salt(LS,0,3%,controls) diet starting at age 7 weeks for 12 weeks(hypertrophy model,H-LVH) or 19 weeks(heart failure model,H-HF).Age-matched rats served as controls and human normal,hypertensive and heart failure myocardial specimen were also examined for changes on the expression and activity of Cat S.Resuits Reverse transcription and real-time polymerase chain reaction analysis revealed significantly upregulated Cat S mRNA in rats with H-HF than in rats with H-LVH or in control rats and Cat S mRNA expression is negetively correlated with LVEF(r=-0.88.P＜0.05).In situ and immunohistochemistry examinations showed that Cat S was localized predominantly in cardiac myocytes(CMCs)and coronary vascular smooth muscle cells(SMC).Elastic lamina fragmentations and Cat S-dependent elastolvtic activity were significantly increased in H-HF-rats.The expression of interleukin-1β was also increased in the LVM of H-HF rats,and this cytokine was found to increase the Cat S protein expression in cultlife neonatal CMCs.Similar results were revealed in human myocardial specimens.Conclusion Elastolytic Cat S might play an important role in the pathogenesis of myocardial remodeling and heart failure and Cat S might serve as a novel therapheutic target in preventing or reversing hypertension induced LV remodeling and heart failure.
