<i>SCARB1</i>
            Gene Variants Are Associated With the Phenotype of Combined High High-Density Lipoprotein Cholesterol and High Lipoprotein (a)

Yang, Xiaoping; Sethi, Amar A.; Yanek, Lisa R.; Knapper, Cathy; Nordestgaard, Børge G.; Tybjærg‐Hansen, Anne; Becker, Diane M.; Mathias, Rasika A.; Remaley, Alan T.; Becker, Lewis C.

doi:10.1161/circgenetics.116.001402

Cited by 31 publications

(24 citation statements)

References 54 publications

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“…For example, SR-BI mostly leads to the selective uptake of neutral lipids, such as cholesteryl esters from the Lp(a) core, but may not significantly alter the plasma clearance of apo(a) (23). The physiologic relevance of these observations on the interaction of Lp(a) with SR-BI in humans is not clear, but patients with heterozygous loss of function mutations in SR-BI show increased plasma levels of Lp(a) (24). LRP1 may contribute to Lp(a) clearance via its affinity for apoB or Lp(a) and the different affinities for apoE isoforms.…”

Section: Specific Research Priorities and Recommendationsmentioning

confidence: 99%

NHLBI Working Group Recommendations to Reduce Lipoprotein(a)-Mediated Risk of Cardiovascular Disease and Aortic Stenosis

Tsimikas

Fazio

Ferdinand

et al. 2018

Journal of the American College of Cardiology

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374

289

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Pathophysiological, epidemiological, and genetic studies provide strong evidence that lipoprotein(a) [Lp(a)] is a causal mediator of cardiovascular disease (CVD) and calcific aortic valve disease (CAVD). Specific therapies to address Lp(a)-mediated CVD and CAVD are in clinical development. Due to knowledge gaps, the National Heart, Lung, and Blood Institute organized a working group that identified challenges in fully understanding the role of Lp(a) in CVD/CAVD. These included the lack of research funding, inadequate experimental models, lack of globally standardized Lp(a) assays, and inadequate understanding of the mechanisms underlying current drug therapies on Lp(a) levels. Specific recommendations were provided to facilitate basic, mechanistic, preclinical, and clinical research on Lp(a); foster collaborative research and resource sharing; leverage expertise of different groups and centers with complementary skills; and use existing National Heart, Lung, and Blood Institute resources. Concerted efforts to understand Lp(a) pathophysiology, together with diagnostic and therapeutic advances, are required to reduce Lp(a)-mediated risk of CVD and CAVD.

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Section: Specific Research Priorities and Recommendationsmentioning

confidence: 99%

NHLBI Working Group Recommendations to Reduce Lipoprotein(a)-Mediated Risk of Cardiovascular Disease and Aortic Stenosis

Tsimikas

Fazio

Ferdinand

et al. 2018

Journal of the American College of Cardiology

Self Cite

374

289

View full text Add to dashboard Cite

show abstract

“…Human SCARB1 gene variants have been shown to be associated with abnormal lipids in women with coronary artery disease (132), and analysis of common genetic variations near the SCARB1 locus shows significant association with plasma HDL-C levels (133), as well as with combined high HDL-C and high lipoprotein (a) (134). Intestinal SR-B1 is upregulated in the insulin-resistant state and is associated with overproduction of intestinal apoB48-containing lipoproteins (135).…”

Section: Sr-b1 Function In Other Pathophysiological Conditionsmentioning

confidence: 99%

SR-B1: A Unique Multifunctional Receptor for Cholesterol Influx and Efflux

Shen

Azhar²,

Kraemer³

2018

Annu. Rev. Physiol.

284

253

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The scavenger receptor, class B type 1 (SR-B1), is a multiligand membrane receptor protein that functions as a physiologically relevant high-density lipoprotein (HDL) receptor whose primary role is to mediate selective uptake or influx of HDL-derived cholesteryl esters into cells and tissues. SR-B1 also facilitates the efflux of cholesterol from peripheral tissues, including macrophages, back to liver. As a regulator of plasma membrane cholesterol content, SR-B1 promotes the uptake of lipid soluble vitamins as well as viral entry into host cells. These collective functions of SR-B1 ultimately affect programmed cell death, female fertility, platelet function, vasculature inflammation, and diet-induced atherosclerosis and myocardial infarction. SR-B1 has also been identified as a potential marker for cancer diagnosis and prognosis. Finally, the SR-B1-linked selective HDL-cholesteryl ester uptake pathway is now being evaluated as a gateway for the delivery of therapeutic and diagnostic agents. In this review, we focus on the regulation and functional significance of SR-B1 in mediating cholesterol movement into and out of cells.

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“…However, the observation that their platelets have increased cholesterol content and are prothrombotic[14] suggests that their HDL has less cholesterol efflux capacity. As in mice, recent studies have demonstrated that human carriers of loss of function SCARBI variants have increased plasma Lp(a) suggesting that hepatic SR-BI also mediates clearance of proatherogenic Lp(a) in humans[34]. However, future studies need to address whether hepatic SR-BI also contributes to the clearance of atherogenic remnant lipoproteins in humans.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the in vivo clearance of Lp(a) was decreased in SR-BI deficient mice and overexpression of hepatic SR-BI markedly increased the clearance of Lp(a)[33]. Importantly, studies showed that human carriers of 6 different SCARB1 gene variants had increased plasma levels of Lp(a), and the variants had reduced ability to mediate the uptake of Lp(a) CE[34]. …”

Section: Effects Of Hepatic Sr-bi On Atherosclerosis and Plasma Lipopmentioning

confidence: 99%

SR-BI: A Multifunctional Receptor in Cholesterol Homeostasis and Atherosclerosis

Linton

Huan

Linton

et al. 2017

Trends in Endocrinology & Metabolism

164

141

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The HDL receptor scavenger receptor class B type I (SR-BI) plays crucial roles in cholesterol homeostasis, lipoprotein metabolism and atherosclerosis. Hepatic SR-BI mediates reverse cholesterol transport (RCT) by the uptake of HDL cholesterol for routing to the bile. Through the selective uptake of HDL lipids, hepatic SR-BI modulates HDL composition and preserves HDL atheroprotective functions of mediating cholesterol efflux and minimizing inflammation and oxidation. Macrophage and endothelial cell SR-BI inhibits the development of atherosclerosis by mediating cholesterol trafficking to minimize atherosclerotic lesion foam cell formation. SR-BI signaling also helps limit inflammation and cell death c 2017 Published by Elsevier Ltd. and mediates efferocytosis of apoptotic cells in atherosclerotic lesions thereby preventing vulnerable plaque formation. SR-BI is emerging as a multifunctional therapeutic target to reduce atherosclerosis development.

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SCARB1 Gene Variants Are Associated With the Phenotype of Combined High High-Density Lipoprotein Cholesterol and High Lipoprotein (a)

Abstract: Lp(a) is a proatherogenic lipoprotein particle containing one mole of apolipoprotein(a) (apo(a)) and a mole of LDL. 15,16

Cited by 31 publications

References 54 publications

NHLBI Working Group Recommendations to Reduce Lipoprotein(a)-Mediated Risk of Cardiovascular Disease and Aortic Stenosis

NHLBI Working Group Recommendations to Reduce Lipoprotein(a)-Mediated Risk of Cardiovascular Disease and Aortic Stenosis

SR-B1: A Unique Multifunctional Receptor for Cholesterol Influx and Efflux

SR-BI: A Multifunctional Receptor in Cholesterol Homeostasis and Atherosclerosis

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