Journal article

Pharmacological inhibition of the NLRP3 inflammasome reduces blood pressure, renal damage, and dysfunction in salt-sensitive hypertension

SM Krishnan, YH Ling, BM Huuskes, DM Ferens, N Saini, CT Chan, H Diep, MM Kett, CS Samuel, BK Kemp-Harper, AAB Robertson, MA Cooper, K Peter, E Latz, AS Mansell, CG Sobey, GR Drummond, A Vinh

Cardiovascular Research | OXFORD UNIV PRESS | Published : 2019

Abstract

Aims Renal inflammation, leading to fibrosis and impaired function is a major contributor to the development of hypertension. The NLRP3 inflammasome mediates inflammation in several chronic diseases by processing the cytokines pro-interleukin (IL)-1β and pro-IL-18. In this study, we investigated whether MCC950, a recently-identified inhibitor of NLRP3 activity, reduces blood pressure (BP), renal inflammation, fibrosis and dysfunction in mice with established hypertension. Methods and results C57BL6/J mice were made hypertensive by uninephrectomy and treatment with deoxycorticosterone acetate (2.4 mg/day, s.c.) and 0.9% NaCl in the drinking water (1K/DOCA/salt). Normotensive controls were uni..

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University of Melbourne Researchers

Grants

Awarded by European Commission


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia (APP1143674 to G.R.D., A.M., C.S., and A.V.; APP1062721 to G.R.D., C.S., A.M. and E.L.; APP1006017 to G.R.D.; APP1079467 to C.G.S.; APP1079492 to K.P.; and APP1041766 to C.S.S.), the European Research Council InflammAct (616777 to E.L.) and the TRR57 grant by the Deutsche Forschungsgemeinschaft (to E.L.).