Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction.
Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome.
Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., 26-1, Muraoka-Higashi 2chome, Fujisawa, Kanagawa 251-8555, Japan.
Makoto
M
Asahina
Fumi
F
Shimizu
Masayuki
M
Ohta
Michiyasu
M
Takeyama
Ryuichi
R
Tozawa
D000818:Animals; D053299:Apolipoprotein B-100 / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D006946:Hyperinsulinism / Q000235:genetics; D006949:Hyperlipidemias / Q000209:etiology; D006973:Hypertension / Q000235:genetics; D007249:Inflammation; D007674:Kidney Diseases / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D050356:Lipid Metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics; D009765:Obesity / Q000235:genetics; D018384:Oxidative Stress; D011507:Proteinuria / Q000235:genetics; D055647:Rats, Transgenic; D017208:Rats, Wistar; D012598:Sclerosis
C569471:APOB protein, human; D053299:Apolipoprotein B-100