Sleep Disorders: Sleep Disorders III |

Inhibition of Rho-Kinase Attenuates Left Ventricular Remodeling in Chronic Intermittent Hypoxia-Induced Rats by Suppressing Myocardial Inflammation and Apoptosis FREE TO VIEW

Zhihua Wang, MA
Author and Funding Information

Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A585. doi:10.1016/j.chest.2016.02.610
Text Size: A A A
Published online

SESSION TITLE: Sleep Disorders III

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: Chronic intermittent hypoxia (CIH), the hallmark of obstructive sleep apnea (OSA), has been reported to play a key role in the development of obstructive sleep apnea-associated cardiovascular diseases including cardiac hypertrophy. RhoA/ROCK pathway could also induce myocardial remodeling, but the exact mechanisms are not fully elucidated. The current study’s purpose is to investigate the influence of hydroxyfasudil, a selective ROCK inhibitor, on CIH-induced left ventricular remodeling in rats and its possible mechanisms.

METHODS: Adult male SD rats were subjected to chronic intermittent hypoxia or normoxia and were treated with hydroxyfasudil (10 mg/kg/day intraperitoneal injection) or the vehicle for 6 weeks. The morphological features of cardiac remodeling were observed using light and electron microscopy. The mRNA expression of TNF-a, IL-6, MCP-1, TGF-b1 and NF-kB p65 was assessed with RT-PCR. The phosphorylation of MYPT1, as well as the protein levels of RhoA, NF-kB p65, Bax, cleaved-caspase3 were evaluated using Western blotting. The extent of cardiomyocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL).

RESULTS: In this study, hydrofasudil treatment significantly protected against intermittent hypoxia-induced histopathologic and ultrastructural changes in rat myocardium. Moreover, hydroxyfasudil effectively inhibited RhoA/ROCK signaling activation and simultaneously down-regulated NF-kB activity, which was accompanied by reduced NF-kB downstream inflammatory genes and up-regulated Bax and cleaved-caspasee3 protein expressions.

CONCLUSIONS: These results suggest that hydroxyfasudil attenuates myocardial remodeling in chronic intermittent hypoxia-induced rats, at least partly by suppressing activation of NF-kB.

CLINICAL IMPLICATIONS: Inhibition of the RhoA/ROCK pathway could become an important therapeutic target in the prevention of Obstructive sleep apnea-related cardiomyopathy.

DISCLOSURE: Zhihua Wang: University grant monies: fund grant

No Product/Research Disclosure Information




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543