Garbern JC, Williams J, Kristl AC, Malick A, Rachmin I, Gaeta B, Ahmed N, Vujic A, Libby P, Lee RT. 2019. Dysregulation of IL-33/ST2 signaling and myocardial periarteriolar fibrosis. Journal of molecular and cellular cardiology. 128:179-186. Pubmed: 30763587 DOI:S0022-2828(18)30888-5


Microvascular dysfunction in the heart and its association with periarteriolar fibrosis may contribute to the diastolic dysfunction seen in heart failure with preserved ejection fraction. Interleukin-33 (IL-33) prevents global myocardial fibrosis in a pressure overloaded left ventricle by acting via its receptor, ST2 (encoded by the gene, Il1rl1); however, whether this cytokine can also modulate periarteriolar fibrosis remains unclear. We utilized two approaches to explore the role of IL-33/ST2 in periarteriolar fibrosis. First, we studied young and old wild type mice to test the hypothesis that IL-33 and ST2 expression change with age. Second, we produced pressure overload in mice deficient in IL-33 or ST2 by transverse aortic constriction (TAC). With age, IL-33 expression increased and ST2 expression decreased. These alterations accompanied increased periarteriolar fibrosis in aged mice. Mice deficient in ST2 but not IL-33 had a significant increase in periarteriolar fibrosis following TAC compared to wild type mice. Thus, loss of ST2 signaling rather than changes in IL-33 expression may contribute to periarteriolar fibrosis during aging or pressure overload, but manipulating this pathway alone may not prevent or reverse fibrosis.
Copyright © 2019 Elsevier Ltd. All rights reserved.

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Jessica is focused on developing immunocompatible, mature cardiomyocytes derived from induced pluripotent stem cells for future clinical translation.

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Rich Lee seeks to understand heart failure and metabolic diseases that accompany human aging, and translate that understanding into therapies. Lee is an active clinician, regularly treating patients at Brigham and Women’s Hospital.

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