1. [Association between lysosomal cysteine protease cathepsin's activation and left ventricular function and remodeling in hypertensive heart failure rats]
- Author
-
Xian-Wu, Cheng, Jie, Zhang, Hui, Song, Guang, Yang, Xiao-Zhi, Qin, Li-Ke, Guan, Hai, Jin, Kenji, Okumura, and Toyoaki, Murohara
- Subjects
Adult ,Heart Failure ,Male ,Rats, Inbred Dahl ,Ventricular Remodeling ,Myocardium ,Middle Aged ,Cathepsins ,Ventricular Function, Left ,Rats ,Enzyme Activation ,Disease Models, Animal ,Case-Control Studies ,Hypertension ,Animals ,Humans ,Aged - Abstract
To observe myocardial cathepsin (Cat) S expression and activity in hypertensive heart failure rats.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.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 negatively correlated with LVEF (r = -0.88, P0.05). 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 elastolytic activity were significantly increased in H-HF-rats. The expression of interleukin-1 beta was also increased in the LVM of H-HF rats, and this cytokine was found to increase the Cat S protein expression in culture neonatal CMCs. Similar results were revealed in human myocardial specimens.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 therapeutic target in preventing or reversing hypertension induced LV remodeling and heart failure.
- Published
- 2008