Overexpression of interleukin-18 aggravates cardiac fibrosis and diastolic dysfunction in fructose-fed rats.
Inflammation plays an important role in the pathophysiology of the metabolic syndrome (MS). We determined whether the overexpression of interleukin (IL)-18 could aggravate left ventricular (LV) remodeling and diastolic dysfunction in fructose-fed rats (FFRs). To create an animal model for MS, male Wistar rats received 10% fructose in water for 8 months. We used an adenovirus encoding rat IL-18 to overexpress IL-18 in FFRs by intravenous administration. IL-18 overexpression led to increases in collagen volume fraction and collagen deposition. LV systolic function was unaltered. But the LV end-diastolic pressure and the time constant of isovolumic relaxation (tau) were increased. Peak negative value of time derivative of LV pressure (-dp/dt) was decreased. Isovolumic relaxation time and myocardial index, as assessed by echocardiography, were increased. Overexpression of IL-18 leads to aggravated LV remodeling and dysfunction in FFRs. Attenuation of the inflammatory process may provide a novel therapeutic strategy in treating metabolic cardiomyopathy.
Xing
Shan-Shan
SS
Department of Cardiology, QiLu Hospital, Shandong University, Jinan, China.
Bi
Xiu-Ping
XP
Tan
Hong-Wei
HW
Zhang
Yun
Y
Xing
Qi-Chong
QC
Zhang
Wei
W
D000818:Animals; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000503:physiopathology*; D004452:Echocardiography; D005355:Fibrosis / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D005632:Fructose / Q000008:administration & dosage / Q000378:metabolism; D054144:Heart Failure, Diastolic / Q000000981:diagnostic imaging / Q000503:physiopathology*; D020382:Interleukin-18 / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000503:physiopathology*; D020257:Ventricular Remodeling
D020382:Interleukin-18; D005632:Fructose