Faculty Collaboration Database

Interleukin 6 mediates myocardial fibrosis, concentric hypertrophy, and diastolic dysfunction in rats. Hypertension 2010 Aug;56(2):225-31

Date

07/08/2010

Pubmed ID

20606113

Pubmed Central ID

PMC2921860

DOI

10.1161/HYPERTENSIONAHA.109.148635

Scopus ID

2-s2.0-77955500182 (requires institutional sign-in at Scopus site)   386 Citations

Abstract

Although there is a correlation between hypertension and levels of interleukin (IL) 6, the exact role this cytokine plays in myocardial remodeling is unknown. This is complicated by the variable tissue and circulating levels of IL-6 reported in numerous experimental models of hypertension. Accordingly, we explored the hypothesis that elevated levels of IL-6 mediate adverse myocardial remodeling. To this end, adult male Sprague-Dawley rats were infused with IL-6 (2.5 microg . kg(-1) . h(-1), IP) for 7 days via osmotic minipump and compared with vehicle-infused, aged-matched controls. Left ventricular function was evaluated using a blood-perfused isolated heart preparation. Myocardial interstitial collagen volume fraction and isolated cardiomyocyte size were also assessed. Isolated adult cardiac fibroblast experiments were performed to determine the importance of the soluble IL-6 receptor in mediating cardiac fibrosis. IL-6 infusions in vivo resulted in concentric left ventricular hypertrophy, increased ventricular stiffness, a marked increase in collagen volume fraction (6.2% versus 1.7%; P<0.001), and proportional increases in cardiomyocyte width and length, all independent of blood pressure. The soluble IL-6 receptor in combination with IL-6 was found to be essential to producing increased collagen concentration by isolated cardiac fibroblasts and also played a role in mediating a phenotypic conversion to myofibroblasts. These novel observations demonstrate that IL-6 induces a myocardial phenotype almost identical to that of the hypertensive heart, identifying IL-6 as potentially important in this remodeling process.

Author List

Meléndez GC, McLarty JL, Levick SP, Du Y, Janicki JS, Brower GL

MESH terms used to index this publication - Major topics in bold

Animals
Blotting, Western
Cardiomegaly
Cardiomyopathies
Collagen
Diastole
Heart Ventricles
Interleukin-6
Male
Rats
Rats, Sprague-Dawley
Receptors, Interleukin-6
Ventricular Remodeling