Cardiovascular remodeling and metabolic abnormalities in SHRSP.Z-Lepr(fa)/IzmDmcr rats as a new model of metabolic syndrome.
The purpose of this study was to evaluate whether the spontaneously hypertensive rat SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP fatty) is a useful animal model to clarify molecular mechanisms that underlie metabolic syndrome. We investigated histopathologic changes in the cardiovascular organs and metabolic characteristics of SHRSP fatty rats, which are congenic rats from a cross between SHRSP and Zucker fatty (ZF) rats. The aortic wall and cardiac, carotid, and renal arteries from SHRSP and SHRSP fatty rats were thicker than those of ZF rats. The renal cortex in SHRSP and SHRSP fatty rats showed severe glomerulosclerosis. Pancreatic islands in SHRSP fatty and ZF rats showed marked hyperplasia. Steady-state plasma glucose concentrations were higher in SHRSP fatty than in ZF rats. Non-fasting triglyceride levels in SHRSP fatty rats were higher than in ZF rats. DNA synthesis in cultured vascular smooth muscle cells (VSMCs) from SHRSP fatty and SHRSP rats was significantly higher than that in VSMCs from Wistar-Kyoto (WKY) or ZF rats. Levels of platelet-derived growth factor A-chain and transforming growth factor-beta1 mRNAs were higher in VSMCs from SHRSP fatty and SHRSP than from ZF rats. Microarray analysis identified five genes that were significantly upregulated and four genes that were significantly downregulated in visceral adipose tissue of SHRSP fatty rats compared with levels in control strains (SHRSP and ZF rats). These findings suggest that the combination of hypertension and obesity accelerates vascular remodeling, dyslipidemia, and insulin resistance in metabolic syndrome. The phenotype of SHRSP fatty is similar to that of human metabolic syndrome, and therefore, studies of these rats may help clarify the molecular mechanisms that underlie metabolic syndrome in humans.
Ueno
Takahiro
T
Division of Nephrology and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Takagi
Hiroto
H
Fukuda
Noboru
N
Takahashi
Atsuhiko
A
Yao
En-Hui
EH
Mitsumata
Masako
M
Hiraoka-Yamamoto
Junko
J
Ikeda
Katsumi
K
Matsumoto
Koichi
K
Yamori
Yukio
Y
D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002319:Cardiovascular System / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004822:Epididymis / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D011924:Rats, Zucker; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D010982:Platelet-Derived Growth Factor; D053773:Transforming Growth Factor beta1; C075278:platelet-derived growth factor A