Human smooth muscle cell subpopulations differentially accumulate cholesteryl ester when exposed to native and oxidized lipoproteins
Human smooth muscle cell subpopulations differentially accumulate cholesteryl ester when exposed to native and oxidized lipoproteins
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DOI：
10.1161/01.atv.0000131260.80316.37
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发表时间：
2004-07-01
影响因子：
8.7
通讯作者：
Huff, MW
中科院分区：
文献类型：
--
作者：
Argmann, CA;Sawyez, CG;Huff, MW
背景-血管平滑肌细胞（SMC）表现出不同的表型，新的证据表明这是由固有的不同SMC亚型引起的。最近，Li等人（《循环研究》，2001年，第89期：517 - 525）成功地克隆了2个独特的响应SMC亚群从一个单一的人动脉，我们使用这个独特的资源来测试的假设，不同的SMC亚型是泡沫细胞形成的差异前体。（HTG-VLDL）时，较大的、生长较慢的、梭形的HITB 5 SMC克隆比较小的、生长较快的上皮样形状的HITA 2 SMC克隆积累了更多的胆固醇酯（CE）和甘油三酯（TG）（10 μ g CE/mg细胞蛋白[PN]和60 μ g TG/mg PN与7 μ g TG/mg PN，P < 0.05）。脂蛋白脂酶（LPL）是参与脂蛋白摄取的关键酶，被鉴定为改变HITA 2 SMCs脂质蓄积倾向的差异表达蛋白。尽管HITB 5 SMC分泌的LPL显著多于HITA 2 SMC（0.7对0.2 U/mL培养基，P < 0.05），但向HITA 2 SMC添加牛乳LPL显著增加了天然和氧化HTG-VLDL诱导的脂质蓄积。此外，环境可以影响SMC亚群对致动脉粥样硬化脂蛋白的反应。
Background - Vascular smooth muscle cells (SMCs) manifest diverse phenotypes and emerging evidence suggests this is caused by inherently distinct SMC subtypes. Recently, Li et al (Circ Res 2001; 89: 517 - 525) successfully cloned 2 uniquely responsive SMC subpopulations from a single human artery and we used this unique resource to test the hypothesis that distinct SMC subtypes are differential precursors of foam cell formation.Methods and Results - When challenged with human atherogenic native or oxidized hypertriglyceridemic very-low-density lipoprotein (HTG-VLDL), the larger, slower-growing, spindle-shaped HITB5 SMC clone accumulated significantly more cholesteryl ester (CE) and triglyceride (TG) than the smaller, faster-growing epithelioid-shaped HITA2 SMC clone (10 versus 2 mug CE/mg cell protein [PN] and 60 versus 7 mug TG/mg PN, P < 0.05). Lipoprotein lipase (LPL), a key enzyme involved in lipoprotein uptake, was identified as one differentially expressed protein that altered the predisposition of HITA2 SMCs for lipid accumulation. Although HITB5 SMCs secreted significantly more LPL than did HITA2 SMCs (0.7 versus 0.2 U/mL media, P < 0.05), the addition of bovine milk LPL to HITA2 SMCs, significantly increased native and oxidized HTG-VLDL - induced lipid accumulation.Conclusions - Inherently distinct SMC subsets are differentially predisposed to lipoprotein-induced lipid accumulation. Moreover, the environment can influence the response of SMC subsets to atherogenic lipoproteins.