Proteomic Determinants of Variation in Cholesterol Efflux: Observations from the Dallas Heart Study.
Proteomic Determinants of Variation in Cholesterol Efflux: Observations from the Dallas Heart Study.
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DOI：
10.3390/ijms242115526
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发表时间：
2023-10-24
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
高密度脂蛋白（HDL）是预测和治疗动脉粥样硬化性心血管疾病（ASCVD）的有希望的靶点，因为它们介导从积聚在血管系统中的载脂巨噬细胞中清除过量胆固醇。HDL的这种功能特性，称为胆固醇流出能力（CEC），与ASCVD呈负相关。HDL在组成上是多样的，与>250种不同的蛋白质相关联，但它们对CEC的相对贡献仍然知之甚少。我们的目标是确定和定义调节人类CEC的关键HDL相关蛋白。在基于多种族人群的达拉斯心脏研究（DHS）队列中，对36名在15年内表现出持续极高（>=90th%）或极低（<=10th%）CEC的个体的血浆HDL蛋白质组特征进行了定量。在高CEC组（r分别为0.49、0.41和-0.21）和低CEC组（r分别为-0.46、-0.41和0.66）中，载脂蛋白（Apo）A-I相关ApoC-II、ApoC-III和ApoA-IV水平与CEC差异相关（异质性p（pHet）分别为0.03、0.04和0.003）。此外，我们观察到，在低CEC组中，ApoA-I、ApoC-III、补体C3（CO 3）、ApoE和纤溶酶原（PLMG）的水平与CEC呈负相关（对于具有这些蛋白质的亚种，r =-0.11至-0.25;对于缺乏这些蛋白质的亚种，r = 0.58至0.65;异质性p < 0.05）。这些发现表明，HDL上特定蛋白的富集，从而HDL的不同亚种，差异调节胆固醇从血管系统中的去除。
High-density lipoproteins (HDLs) are promising targets for predicting and treating atherosclerotic cardiovascular disease (ASCVD), as they mediate removal of excess cholesterol from lipid-laden macrophages that accumulate in the vasculature. This functional property of HDLs, termed cholesterol efflux capacity (CEC), is inversely associated with ASCVD. HDLs are compositionally diverse, associating with >250 different proteins, but their relative contribution to CEC remains poorly understood. Our goal was to identify and define key HDL-associated proteins that modulate CEC in humans. The proteomic signature of plasma HDL was quantified in 36 individuals in the multi-ethnic population-based Dallas Heart Study (DHS) cohort that exhibited persistent extremely high (>=90th%) or extremely low CEC (<=10th%) over 15 years. Levels of apolipoprotein (Apo)A-I associated ApoC-II, ApoC-III, and ApoA-IV were differentially correlated with CEC in high (r = 0.49, 0.41, and −0.21 respectively) and low (r = −0.46, −0.41, and 0.66 respectively) CEC groups (p for heterogeneity (pHet) = 0.03, 0.04, and 0.003 respectively). Further, we observed that levels of ApoA-I with ApoC-III, complement C3 (CO3), ApoE, and plasminogen (PLMG) were inversely associated with CEC in individuals within the low CEC group (r = −0.11 to −0.25 for subspecies with these proteins vs. r = 0.58 to 0.65 for subspecies lacking these proteins; p < 0.05 for heterogeneity). These findings suggest that enrichment of specific proteins on HDLs and, thus, different subspecies of HDLs, differentially modulate the removal of cholesterol from the vasculature.
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健康和疾病中的脂质和脂蛋白：专注于靶向动脉粥样硬化。
影响因子：
4.7
作者：
Lee CK;Liao CW;Meng SW;Wu WK;Chiang JY;Wu MS
通讯作者：
Wu MS
影响因子：
4.7
作者：
Florea, Gabriela;Florina Tudorache, Irina;Valeria Fuior, Elena;Ionita, Radu;Dumitrescu, Madalina;Madalina Fenyo, Ioana;Georgeta Bivol, Violeta;Violeta Gafencu, Anca
通讯作者：
Violeta Gafencu, Anca
DOI：
10.1124/jpet.110.167890
发表时间：
2010-08-10
影响因子：
3.5
作者：
Amar, Marcelo J. A.;D'Souza, Wilissa;Remaley, Alan T.
通讯作者：
Remaley, Alan T.
影响因子：
3.6
作者：
Lee JJ;Chi G;Fitzgerald C;Kazmi SHA;Kalayci A;Korjian S;Duffy D;Shaunik A;Kingwell B;Yeh RW;Bhatt DL;Gibson CM
通讯作者：
Gibson CM
DOI：
10.1161/atvbaha.113.301373
发表时间：
2013-07
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Li XM;Tang WH;Mosior MK;Huang Y;Wu Y;Matter W;Gao V;Schmitt D;Didonato JA;Fisher EA;Smith JD;Hazen SL
通讯作者：
Hazen SL