Deficiency of receptor-associated protein attenuates angiotensin II-induced atherosclerosis in hypercholesterolemic mice without influencing abdominal aortic aneurysms.
Deficiency of receptor-associated protein attenuates angiotensin II-induced atherosclerosis in hypercholesterolemic mice without influencing abdominal aortic aneurysms.
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DOI：
10.1016/j.atherosclerosis.2011.11.013
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发表时间：
2012-02
期刊：
影响因子：
5.3
通讯作者：
Daugherty A
中科院分区：
文献类型：
--
作者：
Wang S;Subramanian V;Lu H;Howatt DA;Moorleghen JJ;Charnigo R;Cassis LA;Daugherty A
受体相关蛋白（RAP）最初被描述为低密度脂蛋白受体相关蛋白1 （LRP1）的调节剂，但现在已知可以调节许多蛋白质。由于RAP对血管病理的直接影响尚未研究，本研究确定RAP缺乏是否影响血管紧张素II （AngII）诱导的高胆固醇血症小鼠动脉粥样硬化和腹主动脉瘤（AAAs）。RAP +/+或-/-的雄性低密度脂蛋白受体-/-小鼠在摄入饱和脂肪丰富的饮食的同时注入AngII (500 ng/kg/min) 4周。RAP缺乏对体重或血管血管引起的收缩压升高没有影响。尽管血浆胆固醇浓度升高，但RAP缺乏减少了主动脉弓动脉粥样硬化病变的大小，而对血管损伤诱导的AAAs没有影响。RAP缺乏显著降低了巨噬细胞中LRP1蛋白的丰度，但未改变其在主动脉平滑肌细胞中的丰度。此外，RAP缺乏对巨噬细胞中LRP1或脂蛋白脂肪酶的mRNA丰度没有影响。为了确定白细胞中RAP缺乏是否影响血管粥样硬化，用RAP +/+或-/-雄性小鼠的骨髓来源细胞重新填充辐照的雄性LDL受体-/-小鼠。嵌合小鼠连续4周注射AngII (500 ng/kg/min)，同时饲喂富含饱和脂肪的饲料。骨髓源性细胞RAP缺乏不影响血浆胆固醇浓度或动脉粥样硬化病变大小。全身RAP缺乏可减轻高胆固醇血症小鼠动脉粥样硬化，但不影响灌注AngII的AAAs。抗动脉粥样硬化作用不是由于骨髓源性细胞缺乏RAP。
Receptor-associated protein (RAP) was initially described as a regulator of low density lipoprotein receptor-related protein 1 (LRP1), but is now known to regulate many proteins. Since the direct effects of RAP on vascular pathologies have not been studied, this study determined whether RAP deficiency influenced angiotensin II (AngII)-induced atherosclerosis and abdominal aortic aneurysms (AAAs) in hypercholesterolemic mice. Male LDL receptor -/- mice that were either RAP +/+ or -/- were infused with AngII (500 ng/kg/min) for 4 weeks while consuming a saturated fat-enriched diet. RAP deficiency had no effects on body weight or AngII-induced increases of systolic blood pressure. Despite increased plasma cholesterol concentrations, RAP deficiency reduced atherosclerotic lesion size in aortic arches, while having no effect on AngII-induced AAAs. RAP deficiency profoundly reduced LRP1 protein abundance in macrophages, but did not change its abundance in aortic smooth muscle cells. Also, RAP deficiency had no effects on mRNA abundance of LRP1 or lipoprotein lipase in macrophages. To determine whether RAP deficiency in leukocytes influenced AngII-induced atherosclerosis, irradiated male LDL receptor -/- mice were repopulated with bone marrow-derived cells from either RAP +/+ or -/- male mice. The chimeric mice were infused with AngII (500 ng/kg/min) for 4 weeks while fed the saturated fat-enriched diet. RAP deficiency in bone marrow-derived cells did not influence either plasma cholesterol concentrations or atherosclerotic lesion size. Whole body RAP deficiency attenuated atherosclerosis without influencing AAAs in hypercholesterolemic mice infused with AngII. The anti-atherogenic effect was not attributable to RAP deficiency in bone marrow-derived cells.
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影响因子：
3.7
作者：
Boucher, Philippe;Li, Wei-Ping;Matz, Rachel L.;Takayama, Yoshiharu;Auwerx, Johan;Anderson, Richard G. W.;Herz, Joachim
通讯作者：
Herz, Joachim
DOI：
10.1152/ajpendo.00277.2006
发表时间：
2007-05-01
影响因子：
5.1
作者：
Lu, Hong;Boustany-Kari, Carine M.;Cassis, Lisa A.
通讯作者：
Cassis, Lisa A.
DOI：
10.3791/1291
发表时间：
2009-05-15
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Daugherty, Alan;Rateri, Debra;Balakrishnan, Anju
通讯作者：
Balakrishnan, Anju
影响因子：
20.1
作者：
Owens AP 3rd;Subramanian V;Moorleghen JJ;Guo Z;McNamara CA;Cassis LA;Daugherty A
通讯作者：
Daugherty A
DOI：
10.1161/01.atv.0000249641.96896.e6
发表时间：
2006-12-01
影响因子：
8.7
作者：
Hu, L.;Boesten, L. S. M.;Tamsma, J. T.
通讯作者：
Tamsma, J. T.