Dysregulation of IL-33/ST2 signaling and myocardial periarteriolar fibrosis
| Autor: | Jessica C. Garbern, Peter Libby, Jason B. Williams, Benjamin Gaeta, Ana Vujic, Inbal Rachmin, Nafis Ahmed, Amy C. Kristl, Alyyah Malick, Richard T. Lee |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.medical_treatment Heart Ventricles Diastole IL1RL1 030204 cardiovascular system & hematology Article 03 medical and health sciences Mice 0302 clinical medicine Fibrosis Internal medicine medicine Animals Humans Molecular Biology Pressure overload Heart Failure business.industry Myocardium medicine.disease Interleukin-33 Interleukin-1 Receptor-Like 1 Protein Interleukin 33 Disease Models Animal 030104 developmental biology Cytokine Endocrinology Gene Expression Regulation Myocardial fibrosis Cardiology and Cardiovascular Medicine business Heart failure with preserved ejection fraction Signal Transduction |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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