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논문분류	춘계학술대회 초록집
제목	APOL1 renal risk variants promote cholesterol accumulation in tissues and cultured macrophages from APOL1 transgenic mice
저자	Jung-hwa RYU2, Alessia FORNONI3, Myung SHIN4, Maarten HOEK4, *Jeffrey b. KOPP2
출판정보	2017; 2017(1):
키워드	Apolipoprotein L1; cholesterol efflux; ATP binding cassette transporter A1; ATP binding cassette transporter G1; macrophages; foam cells
초록	Objectives : Apolipoprotein L1 (APOL1) genetic variants G1 and G2, compared to the common allele G0, are major risk factors for non-diabetic kidney disease in African descent populations. APOL1 is a minor protein component of HDL, as well as being expressed in podocytes and vascular cells. Reverse cholesterol transport involves the transport of cholesterol to HDL by cellular ATP-binding cassette; ABCA1 and ABCG1 with subsequent delivery from peripheral tissues to the liver. With impaired RCT, lipid accumulation is occurred and macrophages become foam cells, releasing inflammatory factors. We asked whether the APOL1 risk variants alter peripheral cholesterol metabolism and specifically affect macrophage cholesterol efflux. Methods : Tissues and bone marrow (BM)-derived monocytes were isolated from wild-type mice (WT) and from BAC/APOL1 transgenic (APOL1-G0, APOL1-G1, and APOL1-G2) mice, which carry a bacterial artificial chromosome that contains the human APOL1 genomic region. Monocytes were differentiated into macrophages using M-CSF, and then polarized into M1 and M2 macrophages. Cholesterol quantitation, cholesterol efflux, and ABCA1 and ABCG1 mRNA were measured. Results : Kidney, spleen, and bone marrow-derived macrophages from APOL1-G1 and -G2 mice showed increased cholesterol accumulation and decreased ABCA1 and ABCG1 mRNA levels. The BM-derived macrophages from APOL1- G1 and -G2 mice showed significantly reduced cholesterol efflux compared to WT or APOL1-G0 macrophages. Conclusions : APOL1-G1 and -G2 risk variants impaired peripheral reverse cholesterol transport through decreased expression of cholesterol efflux transporters. This process would tend to promote macrophage foam cell formation, driving inflammation in the glomerulus and renal interstitium.
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