Lutein attenuates angiotensin II- induced cardiac remodeling by inhibiting AP-1/IL-11 signaling.

Abstract

RATIONALE:

Oxidative stress plays a critical role in the development of cardiac remodeling and heart failure. Lutein, the predominant nonvitamin A carotenoid, has been shown to have profound effects on oxidative stress. However, the effect of lutein on angiotensin II (Ang II)-induced cardiac remodeling and heart failure remains unknown.

OBJECTIVE:

The aim of this study was to determine whether lutein is involved in cardiac remodeling and to elucidate the underlying molecular mechanisms.

METHODS AND RESULTS:

In vitro experiments with isolated neonatal rat cardiomyocytes (NRCMs) and cardiac fibroblasts (CFs) revealed that lutein significantly attenuated Ang II-induced collagen expression in CFs, and cardiomyocyte hypertrophy. The Ang II-induced increases in superoxide generation, inflammation and apoptosis in cultured CFs were strikingly prevented by lutein. In vivo, fibrosis, hypertrophic cardiomyocyte and superoxide generation were analyzed, and lutein was demonstrated to confer resistance to Ang II-induced cardiac remodeling in mice. Mechanistically, RNA sequencing revealed that interleukin-11 (IL-11) expression was significantly upregulated in mouse hearts in response to Ang II infusion and was significantly suppressed in the hearts of lutein-treated mice. Furthermore, IL-11 overexpression blocked the effects of lutein on fibrosis and oxidative stress in CFs and impaired the protective effect of lutein on cardiac remodeling. Notably, we discovered that lutein could reduce Ang II-induced IL-11 expression, at least partly through the regulation of activator protein (AP)-1 expression and activity.

CONCLUSIONS:

Lutein has potential as a treatment for cardiac remodeling and heart failure via the suppression of IL-11 expression.

• Authors: Youming Chen, Lan Wang, Shixing Huang, Jiangfeng Ke, Qing Wang, Zhiwen Zhou, Wei Chang
• Journal: Redox biology (Redox Biol) Vol. 44 Pg. 102020 (08 2021) ISSN: 2213-2317 [Electronic] Netherlands
• PMID: 34077894 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier B.V.

Chemical References

• Interleukin-11
• Transcription Factor AP-1
• Angiotensin II
• Lutein

Topics

• Angiotensin II
• Animals
• Cardiomegaly (pathology)
• Fibrosis
• Interleukin-11
• Lutein
• Mice
• Mice, Inbred C57BL
• Myocardium (pathology)
• Rats
• Transcription Factor AP-1
• Ventricular Remodeling