Lentivirus mediated IL-17R blockade improves diastolic cardiac function in spontaneously hypertensive rats

• Published in: Experimental and molecular pathology Vol. 91; no. 1; pp. 362 - 367
• Main Authors: Liu, Wei, Wang, Xueting, Feng, Weiwei, Li, Shuqing, Tian, Wendan, Xu, Tengfei, Song, Yunyan, Zhang, Zhiyi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.08.2011; Elsevier
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiac fibrosis; Cardiology. Vascular system; Collagen Type III - metabolism; Diastolic function; Disease Models, Animal; Disease Progression; Electrocardiography; Fibrosis - etiology; Fibrosis - pathology; Fibrosis - physiopathology; Heart - physiopathology; Heart Failure - prevention & control; Heart Ventricles - metabolism; Heart Ventricles - pathology; Heart Ventricles - physiopathology; Hemodynamics; Humans; Hypertension - metabolism; Hypertension - physiopathology; IL-17RA; Interleukin-17 - metabolism; Investigative techniques, diagnostic techniques (general aspects); Lentivirus - genetics; Male; Matrix Metalloproteinases - metabolism; Medical sciences; Myocardium - metabolism; Myocardium - pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Interleukin-17 - antagonists & inhibitors; Receptors, Interleukin-17 - genetics; Receptors, Interleukin-17 - metabolism; SHR; Tissue Inhibitor of Metalloproteinases - metabolism; Transfection; Diastolic function; Cardiac fibrosis; SHR; IL-17RA; Heart; Hypertension; Cardiac performance; Rat; Rodentia; Cytokine; Retroviridae; Cardiovascular disease; Lentivirus; Virus; Vertebrata; Anatomic pathology; Mammalia; Animal; Fibrosis; Circulatory system
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1016/j.yexmp.2011.04.003

Hypertension 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. Eight-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. Both 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. IL-17/IL-17RA signaling plays an important role in myocardial collagen metabolism in hypertension-induced diastolic dysfunction.