High-Density Lipoproteins, Endothelial Function, and Mendelian Randomization

Westerterp, Marit; Wang, Nan; Tall, Alan R.

doi:10.1161/circresaha.116.309116

Cited by 5 publications

(3 citation statements)

References 22 publications

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“…28, 29 It will be of substantial interest to determine whether carriers of these variants had even better outcomes with anacetrapib in the REVEAL trial. Further analysis of CETP inhibitor clinical trial data, new assays of HDL functionality, 30, 31 as well as clinical outcomes studies based on infusion of reconstituted HDL particles that are highly active in promoting cholesterol efflux 32 may provide additional insights into the complex relationship of HDL to atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

Trials and Tribulations of CETP Inhibitors

Tall

Rader

2018

Circulation Research

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226

153

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The development of CETP inhibitors has had a long and difficult course with three compounds failing in phase III clinical trials. Finally, the REVEAL trial has shown that the CETP inhibitor anacetrapib decreased coronary heart disease when added to statin therapy. While the result is different to earlier studies, this is likely related to the size and duration of the trial. The benefit of anacetrapib appears to be largely explained by lowering of non-HDL cholesterol, rather than increases in HDL cholesterol. Although the magnitude of benefit for CHD appeared to be moderate, in part this may have reflected aspects of the trial design. Anacetrapib treatment was associated with a small increase in BP, but was devoid of major side effects and was also associated with a small reduction in diabetes. Treatment with CETP inhibitors, either alone or in combination with statins, could provide another option for patients with coronary disease who require further reduction in LDL and/or non-HDL cholesterol

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Section: Introductionmentioning

confidence: 99%

Trials and Tribulations of CETP Inhibitors

Tall

Rader

2018

Circulation Research

Self Cite

226

153

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“…These data highlight ABCG1 as a potential therapeutic target in diabetes. Moreover, ABCG1 promotes cholesterol efflux to HDL during reverse cholesterol transport and therefore is considered a critical regulator in various cardiovascular diseases (38). Increasing HDL levels can improve EPC availability in patients with type 2 diabetes mellitus (39).…”

Section: Discussionmentioning

confidence: 99%

Elevating ATP‐binding cassette transporter G1 improves re‐endothelialization function of endothelial progenitor cells via Lyn/Akt/eNOS in diabetic mice

Shi

Liu

et al. 2018

The FASEB Journal

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Endothelial progenitor cell (EPC) dysfunction contributes to diabetes‐induced delay in endothelium repair after vessel injury, prominently associated with diabetic cardiovascular complications such as neointima formation. ATP‐binding cassette transporter G1 (ABCG1) promotes cholesterol efflux to HDL, which may favorably affect EPC function. However, whether ABCG1 improves EPC function, especially in diabetes, remains unknown. Here we investigated the role of ABCG1 in EPCs by using Tie2‐mediated ABCG1 transgenic (Tie2‐ABCG1Tg)mice. Mice were injected with streptozotocin to induce diabetes mellitus. As compared with wild‐type (WT) mice, in Tie2‐ABCG1Tg mice, diabetes‐impaired EPC migration and tube formation were reversed. In vitro gain‐of‐function and loss‐of‐function studies further revealed that ABCG1‐overexpressing EPCs showed increased migration and tube formation and differentiation via the Lck/Yes‐related novel protein tyrosine kinase /Akt/endothelial NO synthase pathway by enhancing cellular cholesterol efflux. Finally, type 1 and type 2 diabetic mouse models with arterial injury were intravenously injected with labeled EPCs from WT or Tie2‐ABCG1Tg mice. Re‐endothelialization in diabetic mice was improved to a greater extent by injection of ABCG1‐overexpressing than WT EPCs. Our study demonstrated that ABCG1 in EPCs improved repair after vascular injury in diabetes by increasing EPC function such as migration, tube formation and differentiation, and subsequent re‐endothelialization. ABCG1 might be a promising therapeutic target for diabetes‐associated vascular diseases.—Shi, Y., Lv, X., Liu, Y., Li, B., Liu, M., Yan, M., Liu, Y., Li, Q., Zhang, X., He, S., Zhu, M., He, J., Zhu, Y., Zhu, Y., Ai, D. Elevating ATP‐binding cassette transporter G1 improves re‐endothelialization function of endothelial progenitor cells via Lyn/Akt/eNOS in diabetic mice. FASEB J. 32, 6525–6536 (2018). htto://www.fasebj.org

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“…An explanation that comes at first hand is the role of HDL in the activation of endothelial Nitric Oxide Synthetase (eNOS). The HDL/Apo A-1 complex directly stimulates nitric oxide production by direct eNOS activation and prevention of eNOS uncoupling 12. As Apo A-1 was also shown to be present in the HDL-4 subfraction, this may suggest that the increase in the HDL-4 subfraction of lipoproteins serves as an endogenous vasodilator that delays disease progression.…”

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confidence: 98%