Rosiglitazone attenuates myocardial remodeling in spontaneously hypertensive rats.
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.
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Shandong, China.
Yun
Y
Ti
Ming-Xiu
MX
Hao
Chuan-Bao
CB
Li
Zhi-Hao
ZH
Wang
Xiao-Yang
XY
Hou
Xue-Qiang
XQ
Zhao
Jun-Ni
JN
Liu
Wei
W
Zhang
Yun
Y
Zhang
Pei-Li
PL
Bu
D000818:Animals; D024042:Collagen Type I / Q000096:biosynthesis; D024061:Collagen Type III / Q000096:biosynthesis; D006973:Hypertension / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D016328:NF-kappa B / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000096:biosynthesis; D016896:Treatment Outcome; D014463:Ultrasonography; D015854:Up-Regulation / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
D024042:Collagen Type I; D024061:Collagen Type III; D007004:Hypoglycemic Agents; D016328:NF-kappa B; D045162:Thiazolidinediones; D019715:Tissue Inhibitor of Metalloproteinase-1; D018808:Transcription Factor AP-1; D000077154:Rosiglitazone; D020780:Matrix Metalloproteinase 9