Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunction without affecting blood pressure in angiotensin II-high salt-induced hypertension. J Hypertens 2015 Jan;33(1):144-52
Date
10/12/2014Pubmed ID
25304471Pubmed Central ID
PMC4256143DOI
10.1097/HJH.0000000000000358Scopus ID
2-s2.0-84916897951 (requires institutional sign-in at Scopus site) 84 CitationsAbstract
OBJECTIVE: Inflammation has been proposed as a key component in the development of hypertension and cardiac remodeling associated with different cardiovascular diseases. However, the role of the proinflammatory cytokine interleukin-6 in the chronic stage of hypertension is not well defined. Here, we tested the hypothesis that deletion of interleukin-6 protects against the development of hypertension, cardiac inflammation, fibrosis, remodeling and dysfunction induced by high salt diet and angiotensin II (Ang II).
METHODS: Male C57BL/6J and interleukin-6-knock out (KO) mice were implanted with telemetry devices for blood pressure (BP) measurements, fed a 4% NaCl diet, and infused with either vehicle or Ang II (90 ng/min per mouse subcutaneously) for 8 weeks. We studied BP and cardiac function by echocardiography at baseline, 4 and 8 weeks.
RESULTS: Myocyte cross-sectional area (MCSA), macrophage infiltration, and myocardial fibrosis were also assessed. BP increased similarly in both strains when treated with Ang II and high salt (Ang II-high salt); however, C57BL/6J mice developed a more severe decrease in left ventricle ejection fraction, fibrosis, and macrophage infiltration compared with interleukin-6-KO mice. No differences between strains were observed in MCSA, capillary density and MCSA to capillary density ratio.
CONCLUSION: In conclusion, absence of interleukin -6 did not alter the development of Ang II-high salt-induced hypertension and cardiac hypertrophy, but it prevented the development of cardiac dysfunction, myocardial inflammation, and fibrosis. This indicates that interleukin-6 plays an important role in hypertensive heart damage but not in the development of hypertension.
Author List
González GE, Rhaleb NE, D'Ambrosio MA, Nakagawa P, Liu Y, Leung P, Dai X, Yang XP, Peterson EL, Carretero OAAuthor
Pablo Nakagawa PhD Assistant Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AlbuminsAngiotensin II
Animals
Blood Pressure
Cardiomegaly
Echocardiography
Fibrosis
Heart
Heart Rate
Hypertension
Inflammation
Interleukin-6
Macrophages
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardium
Myocytes, Cardiac
Phenotype
Sodium Chloride, Dietary
