Lentivirus mediated IL-17R blockade improves diastolic cardiac function in spontaneously hypertensive rats |
| |
Authors: | Liu Wei Wang Xueting Feng Weiwei Li Shuqing Tian Wendan Xu Tengfei Song Yunyan Zhang Zhiyi |
| |
Affiliation: | aDepartment of Cardiology, the first affiliated hospital of Harbin Medical University, Harbin 150001, China;bHarbin Children’s Hospital 150020, China;cDepartment of Rheumatology and Immunology, the first affiliated hospital of Harbin Medical University. Harbin 150001. China |
| |
Abstract: | BackgroundHypertension causes cardiac fibrosis characterized by low-grade inflammation. We hypothesized that proinflammatory cytokine, interleukin-17 (IL-17) is important in hypertensive cardiac fibrosis. The pre-ligand assembly domain (PLAD) of IL-17 receptor A (IL-17RA) mediates receptor–chain associations essential for signaling. This study was designed to explore the role of IL-17 RA PLAD in hypertension-induced cardiac fibrosis.MethodsEight-week-old male spontaneously hypertensive rats (SHRs) were divided into 2 groups, depending on receiving IL-17RA PLAD-Ig or green fluorescent protein (GFP) lentivirus. Age-matched Wistar Kyoto rats served as controls. Cardiac function was determined by echocardiography. Cardiac hypertrophy and fibrosis were histopathologically examined. Matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) expression were quantified by immunoblotting. Collagen content was quantified.ResultsBoth cardiac systolic and diastolic function and myocardial fibrosis in SHRs was improved significantly by the IL-17RA PLAD. Expression of MMP-2 and MMP-9, TIMP-1 and − 2, type I and type III collagen were statistically decreased by IL-17RA PLAD-Ig treatment. Collagen quantitation, as well as collagen concentration and collagen cross-linking, were reduced by IL-17/IL-17R signal blockade.ConclusionsIL-17/IL-17RA signaling plays an important role in myocardial collagen metabolism in hypertension-induced diastolic dysfunction. |
| |
Keywords: | IL-17RA SHR Diastolic function Cardiac fibrosis |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|