Association between lysosomal cysteine protease cathepsin's activation and left ventricular function and remodeling in hypertensive heart failure rats / 中华心血管病杂志
Chinese Journal of Cardiology
;
(12): 51-56, 2008.
Article
Dans Chinois
| WPRIM
| ID: wpr-299499
ABSTRACT
<p><b>OBJECTIVE</b>To observe myocardial cathepsin (Cat) S expression and activity in hypertensive heart failure rats.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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, 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 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.</p><p><b>CONCLUSION</b>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.</p>
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Cathepsines
/
Études cas-témoins
/
Fonction ventriculaire gauche
/
Rats de lignée Dahl
/
Remodelage ventriculaire
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Modèles animaux de maladie humaine
/
Activation enzymatique
/
Défaillance cardiaque
/
Hypertension artérielle
/
Métabolisme
Type d'étude:
Étude observationnelle
/
Facteurs de risque
Limites du sujet:
Animaux
/
Humains
/
Mâle
langue:
Chinois
Texte intégral:
Chinese Journal of Cardiology
Année:
2008
Type:
Article
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