期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 128, 期 -, 页码 179-186出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2019.01.018
关键词
Interleukin-33; ST2; Myocardial fibrosis; Periarteriolar fibrosis; Pressure overload; Aging
资金
- National Institutes of Health [1R01AG047131, 1R0HL119230, HL080472]
- RRM Charitable Fund
- John S. LaDue Memorial Fellowship (Harvard Medical School)
- NIH T32 Fellowship [2T32HL007604, 5T32HL007572-33]
- European Molecular Biology Organization (EMBO) post-doctoral fellowship
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据