Blockade of MyD88 attenuates cardiac hypertrophy and decreases cardiac myocyte apoptosis in pressure overload-induced cardiac hypertrophy in vivo
| Autor: | Jing Ma, Aiqiu Zhao, Fang Hua, Georges E. Haddad, I. William Browder, Xiang Gao, Tuanzhu Ha, Chuanfu Li, Yuehua Li, David L. Williams, Race L. Kao, Jim Kelley |
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| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Physiology Apoptosis Cardiomegaly Biology Severity of Illness Index Rats Sprague-Dawley In vivo Physiology (medical) Internal medicine medicine Animals Myocyte Myocytes Cardiac Cells Cultured Adaptor Proteins Signal Transducing Pressure overload Cardiac myocyte Rats Blockade Hypertension Myeloid Differentiation Factor 88 Cardiology Signal transduction Cardiology and Cardiovascular Medicine |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 290:H985-H994 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00720.2005 |
| Popis: | In this study, we evaluated whether blocking myeloid differentiation factor-88 (MyD88) could decrease cardiac myocyte apoptosis following pressure overload. Adenovirus expressing dominant negative MyD88 (Ad5-dnMyD88) or Ad5-green fluorescent protein (GFP) (Ad5-GFP) was transfected into rat hearts ( n = 8/group) immediately followed by aortic banding for 3 wk. One group of rats ( n = 8) was subjected to aortic banding for 3 wk without transfection. Sham surgical operation ( n = 8) served as control. The ratios of heart weight to body weight (HW/BW) and heart weight to tibia length (HW/TL) were calculated. Cardiomyocyte size was examined by FITC-labeled wheat germ agglutinin staining of membranes. Cardiac myocyte apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, and myocardial interstitial fibrosis was examined by Masson's Trichrome staining. Aortic banding significantly increased the HW/BW by 41.0% (0.44 ± 0.013 vs. 0.31 ± 0.008), HW/TL by 47.2% (42.7 ± 1.30 vs. 29.0 ± 0.69), cardiac myocyte size by 49.6%, and cardiac myocyte apoptosis by 11.5%, and myocardial fibrosis and decreased cardiac function compared with sham controls. Transfection of Ad5-dnMyD88 significantly reduced the HW/BW by 18.2% (0.36 ± 0.006 vs. 0.44 ± 0.013) and HW/TL by 22.3% (33.2 ± 0.95 vs. 42.7 ± 1.30) and decreased cardiomyocyte size by 56.8%, cardiac myocyte apoptosis by 76.2%, as well as fibrosis, and improved cardiac function compared with aortic-banded group. Our results suggest that MyD88 is an important component in the Toll-like receptor-4-mediated nuclear factor-κB activation pathway that contributes to the development of cardiac hypertrophy. Blockade of MyD88 significantly reduced cardiac hypertrophy, cardiac myocyte apoptosis, and improved cardiac function in vivo. |
| Databáze: | OpenAIRE |
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