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Different Roles of PPAR-γ Activity on Physiological and Pathological Alteration After Myocardial Ischemia

Nagashima, Ayako MD*; Watanabe, Ryo BS*; Ogawa, Masahito MS; Suzuki, Jun-ichi MD, PhD; Masumura, Mayumi MD*; Hishikari, Keiichi MD*; Shimizu, Tomoko PhD; Takayama, Kiyoshi PhD; Hirata, Yasunobu MD, PhD; Nagai, Ryozo MD, PhD§; Isobe, Mitsuaki MD, PhD*

Journal of Cardiovascular Pharmacology: August 2012 - Volume 60 - Issue 2 - p 158–164
doi: 10.1097/FJC.0b013e3182592d7b
Original Article

Background: Telmisartan is an angiotensin II receptor blocker, which acts as a partial agonist of peroxisome proliferator activator receptor-γ (PPAR-γ). Because PPAR-γ initiates a variety of antiinflammatory responses, the effect on myocardial ischemia is to be elucidated.

Methods and Results: The left anterior descending arteries were ligated to induce myocardial infarction in rats. The animals were assigned to 4 groups: (1) control (saline, n = 6), (2) telmisartan (10 mg·kg−1·d−1, n = 6), (3) telmisartan + GW9662 (PPAR-γ-antagonist) (10 mg·kg−1·d−1 of telmisartan and 1 mg·kg−1·d−1 of GW9662, n = 6), and (4) amlodipine (10 mg·kg−1·d−1, n = 8) groups. Telmisartan reduced mean blood pressure compared with that in the control group. There was no statistical difference among the telmisartan, telmisartan + GW9662 and amlodipine groups. The end-diastolic left ventricular diameter was smaller in telmisartan group compared with that in the control group; GW9662 negated the effect of telmisartan. The thickness of the ventricular septum was kept in the telmisartan group compared with that in the control group; GW9662 negated the effect. Histopathologic analyses showed that telmisartan suppressed myocardial fibrosis compared with that of the control, whereas GW9662 negated the telmisartan effect.

Conclusions: Telmisartan suppresses pathological remodeling by PPAR-γ agonistic activities independent of its antihypertensive effects.

*Department of Cardiovascular Medicine, Tokyo Medical and Dental University

Department of Advanced Clinical Science and Therapeutics, University of Tokyo, Bunkyo-ku, Tokyo

NB Health Laboratory, Kamiaoki, Saitama

§Department of Cardiovascular Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Reprints: Jun-ichi Suzuki, MD, PhD, Department of Advanced Clinical Science and Therapeutics, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan (e-mail: junichisuzuki-circ@umin.ac.jp).

The authors declare no conflicts of interest.

Received February 8, 2012

Accepted April 5, 2012

© 2012 Lippincott Williams & Wilkins, Inc.