Augmented Cardiac Hypertrophy in Response to Pressure Overload in Mice Lacking the Prostaglandin I 2 Receptor

Author:

Hara Akiyoshi1,Yuhki Koh-ichi1,Fujino Takayuki1,Yamada Takehiro1,Takayama Koji1,Kuriyama Shuhko1,Takahata Osamu1,Karibe Hideji1,Okada Yuji1,Xiao Chun-Yang1,Ma Hong1,Narumiya Shuh1,Ushikubi Fumitaka1

Affiliation:

1. From the Department of Pharmacology, Asahikawa Medical College, Asahikawa (A.H., K.Y., T.F., T.Y., K.T., S.K., O.T., H.K., Y.O., C.-Y.X., H.M., F.U.), and the Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto (S.N.), Japan.

Abstract

Background— In the heart, the expressions of several types of prostanoid receptors have been reported. However, their roles in cardiac hypertrophy in vivo remain unknown. We intended to clarify the roles of these receptors in pressure overload–induced cardiac hypertrophy using mice lacking each of their receptors. Methods and Results— We used a model of pressure overload–induced cardiac hypertrophy produced by banding of the transverse aorta in female mice. In wild-type mice subjected to the banding, cardiac hypertrophy developed during the observation period of 8 weeks. In mice lacking the prostaglandin (PG) I 2 receptor (IP −/− ), however, cardiac hypertrophy and cardiomyocyte hypertrophy were significantly greater than in wild-type mice at 2 and 4 weeks but not at 8 weeks, whereas there was no such augmentation in mice lacking the prostanoid receptors other than IP. In addition, cardiac fibrosis observed in wild-type hearts was augmented in IP −/− hearts, which persisted for up to 8 weeks. In IP −/− hearts, the expression level of mRNA for atrial natriuretic peptide, a representative marker of cardiac hypertrophy, was significantly higher than in wild-type hearts. In vitro, cicaprost, an IP agonist, reduced platelet-derived growth factor–induced proliferation of wild-type noncardiomyocytes, although it could not inhibit cardiotrophin-1–induced hypertrophy of cardiomyocytes. Accordingly, cicaprost increased cAMP concentration efficiently in noncardiomyocytes. Conclusions— IP plays a suppressive role in the development of pressure overload–induced cardiac hypertrophy via the inhibition of both cardiomyocyte hypertrophy and cardiac fibrosis. Both effects have been suggested as originating from the action on noncardiomyocytes rather than cardiomyocytes.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3