Molecular Patterns of Extreme and Persistent Cholesterol Efflux Capacity

极端和持续胆固醇流出能力的分子模式

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作者:Ayea El-Ghazali #, Sneha Deodhar #, Suzanne Saldanha, Brooke Smyth, Mark Izbrand, Anamika Gangwar, Mandana Pahlavani, Anand Rohatgi

Approach and results

CEC was previously measured in 2924 participants enrolled in the Dallas Heart Study, a multi-ethnic population-based study from 2000 to 2002. We prospectively recruited those who were below the 10th and above 90th percentile of CEC. Our study revealed that extreme low and high CEC are persistent, robust phenotypes after 15 years of follow-up. Using size exclusion chromatography, CEC to fractionated plasma depleted of apolipoprotein B (fraction-specific CEC) demonstrated significant differences in CEC patterns between persistent high and low efflux groups. Fraction-specific CEC was correlated with fraction-specific total phospholipid but not apolipoprotein A-I, cholesterol, or total protein. These correlations varied across the size distribution and differed among persistent high versus low efflux groups. Conclusions: Extreme high and low CEC are persistent and robust phenotypes. CEC patterns in fractionated plasma reveal marked variation across the size distribution. Future studies are warranted to determine specific molecular species linked to CEC in a size-specific manner.

Conclusions

Extreme high and low CEC are persistent and robust phenotypes. CEC patterns in fractionated plasma reveal marked variation across the size distribution. Future studies are warranted to determine specific molecular species linked to CEC in a size-specific manner.

Objective

Cholesterol efflux capacity (CEC), the ability of extracellular acceptors to pick-up cholesterol from macrophages, is a clinically relevant cardiovascular biomarker. CEC is inversely associated with incident atherosclerotic cardiovascular disease events. However, CEC is only modestly associated with HDL-C (high-density lipoprotein cholesterol) levels, which may explain the failure of HDL-C raising therapies to improve atherosclerotic cardiovascular disease outcomes. Determinants of variation in CEC are not well understood. Thus, we sought to establish whether extreme high and low CEC is a robust persistent phenotype and to characterize associations with cholesterol, protein, and phospholipids across the particle size distribution. Approach and

Results

CEC was previously measured in 2924 participants enrolled in the Dallas Heart Study, a multi-ethnic population-based study from 2000 to 2002. We prospectively recruited those who were below the 10th and above 90th percentile of CEC. Our study revealed that extreme low and high CEC are persistent, robust phenotypes after 15 years of follow-up. Using size exclusion chromatography, CEC to fractionated plasma depleted of apolipoprotein B (fraction-specific CEC) demonstrated significant differences in CEC patterns between persistent high and low efflux groups. Fraction-specific CEC was correlated with fraction-specific total phospholipid but not apolipoprotein A-I, cholesterol, or total protein. These correlations varied across the size distribution and differed among persistent high versus low efflux groups. Conclusions: Extreme high and low CEC are persistent and robust phenotypes. CEC patterns in fractionated plasma reveal marked variation across the size distribution. Future studies are warranted to determine specific molecular species linked to CEC in a size-specific manner.

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