Human apolipoprotein B transgenic SHR/NDmcr-cp rats show
exacerbated kidney dysfunction |
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Authors: | Makoto ASAHINA Fumi SHIMIZU Masayuki OHTA Michiyasu TAKEYAMA Ryuichi TOZAWA |
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Institution: | Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., 26-1, Muraoka-Higashi 2chome, Fujisawa, Kanagawa 251-8555, Japan |
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Abstract: | 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. |
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Keywords: | apolipoprotein B dyslipidemia kidney dysfunction metabolic syndrome SHR/NDmcr-cprats |
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