Rosiglitazone attenuates myocardial remodeling in spontaneously hypertensive rats
Autor: | Peili Bu, Xue-Qiang Zhao, Jun-Ni Liu, Yun Ti, Yun Zhang, Wei Zhang, Xiao-Yang Hou, Ming-Xiu Hao, Zhi-Hao Wang, Chuan-Bao Li |
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Rok vydání: | 2011 |
Předmět: |
Male
Agonist medicine.medical_specialty Physiology medicine.drug_class medicine.medical_treatment Peroxisome proliferator-activated receptor Rats Inbred WKY Collagen Type I Muscle hypertrophy Rosiglitazone Pathogenesis Downregulation and upregulation Rats Inbred SHR Internal medicine Internal Medicine medicine Animals Hypoglycemic Agents Receptor Saline Ultrasonography chemistry.chemical_classification Tissue Inhibitor of Metalloproteinase-1 Ventricular Remodeling business.industry NF-kappa B Rats Up-Regulation Transcription Factor AP-1 Collagen Type III Treatment Outcome Endocrinology Matrix Metalloproteinase 9 chemistry Hypertension Hypertrophy Left Ventricular Thiazolidinediones Cardiology and Cardiovascular Medicine business medicine.drug |
Zdroj: | Hypertension Research. 34:354-360 |
ISSN: | 1348-4214 0916-9636 |
Popis: | Rosiglitazone, an important peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, improves left ventricular (LV) hypertrophy in diet-induced hypercholesterolemic rats. However, the effects and underlying mechanisms of rosiglitazone on myocardial remodeling in spontaneous hypertension rats (SHRs) are unclear. Twenty male 8-week-old SHRs were randomly divided into two groups: one treated with oral saline (n=10) and the other treated with rosiglitazone (5 mgkg(-1)day(-1), n=10). Ten age-matched Wistar-Kyoto rats were selected as a normal control group. Echocardiography, immunohistochemistry, real-time reverse transcriptase-PCR and western blot analysis were performed to assess the effects of rosiglitazone. After 16 weeks of treatment, LV hypertrophy was significantly attenuated by rosiglitazone (LV weight/body weight, 2.35±0.11 vs. 2.56±0.14 mgg(-1)). According to the echocardiography results, thickening of the LV wall was reduced, and mid-wall fractional shortening was improved by rosiglitazone. Similarly, the excessive collagen deposition and upregulation of collagen I and collagen III seen in SHRs receiving saline were significantly attenuated in SHRs receiving rosiglitazone. In addition, rosiglitazone treatment increased the activity of matrix metalloproteinase-9 (MMP-9) and normalized the MMP-9/tissue inhibitor of metalloproteinase-1 ratio. Furthermore, activator protein-1 (AP-1) activation and nuclear factor-kappa B (NF-κB) expression were suppressed in the rosiglitazone-treated group. These results demonstrate that the PPAR-γ agonist rosiglitazone had beneficial effects on myocardial remodeling in SHRs by way of decreasing AP-1 activation and NF-κB expression, which may help in further inhibiting transcription of the downstream genes involved in the pathogenesis of myocardial remodeling induced by hypertension. |
Databáze: | OpenAIRE |
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