Preventing progression of cardiac hypertrophy and development of heart failure by paricalcitol therapy in rats
| Autor: | Qingen Ke, S. Ananth Karumanchi, Ravi Thadhani, Bhargavi Yalamarti, Soochan Bae, Sangita Choudhury, Peter M. Kang, Hyeon Yu, Paul E. Kroeger |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Paricalcitol medicine.medical_specialty Protein Kinase C-alpha Physiology Hemodynamics Cardiomegaly vitamin D deficiency Rats Sprague-Dawley Physiology (medical) Internal medicine medicine Vitamin D and neurology Animals Enalapril Heart Failure Calcium metabolism business.industry Gene Expression Profiling Original Articles medicine.disease Rats Ergocalciferol Endocrinology Heart failure Ergocalciferols Disease Progression Cardiology Calcium Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Cardiovascular Research. 91:632-639 |
| ISSN: | 1755-3245 0008-6363 |
| DOI: | 10.1093/cvr/cvr133 |
| Popis: | Aims Vitamin D deficiency is associated with cardiac hypertrophy and heart failure, and vitamin D therapy prevents the progression of cardiac hypertrophy in animal models. Here, we examine whether vitamin D therapy prevents progression of pre-existing cardiac hypertrophy and development of heart failure. Methods and results When male Dahl salt-sensitive rats were fed a high salt (HS) diet, all rats developed cardiac hypertrophy after 5 weeks. Thereafter, rats were treated with vehicle (V), paricalcitol (PC, an active vitamin D analogue, at 200 ng, IP 3x/week), enalapril (EP, 90 μg/day), and PC + EP. All groups were continued on the HS diet and evaluated after 4 weeks of therapy. The PC and PC + EP groups, but not the V and EP only groups, showed significant prevention of progression of pre-existing cardiac hypertrophy. The signs of decompensated heart failure were evident in the vehicle-treated group; these heart failure parameters significantly improved with PC, EP or PC + EP therapy. The expression of PKCα, which is regulated by Ca2+and known to stimulate cardiac hypertrophy, was significantly increased in the vehicle group, and PC, EP or PC + EP effectively decreased PKCα activation. We also observed normalization of genetic alterations during progression to heart failure with PC treatment. Conclusion PC treatment resulted in both the prevention of progression of pre-existing cardiac hypertrophy and the development of heart failure, compared with improvement in progression to heart failure by EP alone. These beneficial findings in heart were associated with inhibition of PKCα activation and reversal of gene alterations. |
| Databáze: | OpenAIRE |
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