Prevention and reversal of cardiac hypertrophy by soluble epoxide hydrolase inhibitors.

Prevention and reversal of cardiac hypertrophy by soluble epoxide hydrolase inhibitors. Research Abstract Details 

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Prevention and reversal of cardiac hypertrophy by soluble epoxide hydrolase inhibitors. Abstract Text:

Danyan Xu,Ning Li,Yuxia He,Valeriy Timofeyev,Ling Lu,Hsing-Ju Tsai,In-Hae Kim,Dipika Tuteja,Robertino Karlo P Mateo,Anil Singapuri,Benjamin B Davis,Reginald Low,Bruce D Hammock,Nipavan Chiamvimonvat,

Sustained cardiac hypertrophy represents one of the most common causes leading to cardiac failure. There is emerging evidence to implicate the involvement of NF-kappaB in the development of cardiac hypertrophy. However, several critical questions remain unanswered. We tested the use of soluble epoxide hydrolase (sEH) inhibitors as a means to enhance the biological activities of epoxyeicosatrienoic acids (EETs) to treat cardiac hypertrophy. sEH catalyzes the conversion of EETs to form the corresponding dihydroxyeicosatrienoic acids. Previous data have suggested that EETs may inhibit the activation of NF-kappaB-mediated gene transcription. We directly demonstrate the beneficial effects of several potent sEH inhibitors (sEHIs) in cardiac hypertrophy. Specifically, we show that sEHIs can prevent the development of cardiac hypertrophy using a murine model of pressure-induced cardiac hypertrophy. In addition, sEHIs reverse the preestablished cardiac hypertrophy caused by chronic pressure overload. We further demonstrate that these compounds potently block the NF-kappaB activation in cardiac myocytes. Moreover, by using in vivo electrophysiologic recordings, our study shows a beneficial effect of the compounds in the prevention of cardiac arrhythmias that occur in association with cardiac hypertrophy. We conclude that the use of sEHIs to increase the level of the endogenous lipid epoxides such as EETs may represent a viable and completely unexplored avenue to reduce cardiac hypertrophy by blocking NF-kappaB activation.

Prevention and reversal of cardiac hypertrophy by soluble epoxide hydrolase inhibitors. Publishing Authors By Initials

D Xu,N Li,Y He,V Timofeyev,L Lu,HJ Tsai,IH Kim,D Tuteja,RK Mateo,A Singapuri,BB Davis,R Low,BD Hammock,N Chiamvimonvat,

For similar natural sciences: chemistry: chemistry, physical: solubility research abstracts see: natural sciences: chemistry: chemistry, physical: solubility research

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Prevention and reversal of cardiac hypertrophy by soluble epoxide hydrolase inhibitors. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 103

Page Numbers: 18733-8

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 27

MONTH: 11

YEAR: 2006

Prevention and reversal of cardiac hypertrophy by soluble epoxide hydrolase inhibitors. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Prevention and reversal of cardiac hypertrophy by soluble epoxide hydrolase inhibitors. Keywords Mesh Terms:

KEYWORDS: Solubility

MESH TERMS: antagonists & inhibitors

Chemical & Substance for Abstract: Prevention and reversal of cardiac hypertrophy by soluble epoxide hydrolase inhibitors. Information

Substance Name: Epoxide Hydrolases

Registry Number: EC 3.3.2.3

Grant and Affiliation Information for Prevention and reversal of cardiac hypertrophy by soluble epoxide hydrolase inhibitors.

AFFILIATION: Division of Cardiovascular Medicine, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA.

Country: United States

AGENCY: United States NIEHS

GRANT: R37 ES 02710

ACRONYM: ES

MEDLINETA: Proc Natl Acad Sci U S A

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