Impairment of the Ability of HDL From Patients With Metabolic Syndrome but Without Diabetes Mellitus to Activate eNOS

Denimal, Damien; Monier, Serge; Brindisi, Marie‐Claude; Petit, Jean‐Michel; Bouillet, Benjamin; Nguyen, Amandine; Demizieux, Laurent; Simoneau, Isabelle; Barros, Jean‐Paul Pais de; Vergès, Bruno; Duvillard, Laurence

doi:10.1161/atvbaha.117.309287

Cited by 49 publications

(40 citation statements)

References 35 publications

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“…Table 1. Compositional and functional changes of HDL in pathological conditions ACS, CAD HDL-mediated cholesterol efflux [196]; HDL-mediated NO stimulation [94]; inhibition of superoxide production [94]; antiinflammatory properties and pro-inflammatory properties [94]; endothelial repair [94]; PON1 activity [94]; inhibition of endothelial apoptosis, pro-apoptotic pathways [135]; clusterin content [135], apoC-III content [135,214]; apoA-IV, SAA and complement C3 content [213] FH HDL-C levels; HDL-mediated cholesterol efflux [197,217]; antioxidant properties [201]; anti-inflammatory activity [201,217]; TG and sphingomyelin content [216] T2DM HDL-C levels; pre-ß1 HDL [198]; ABCA1-mediated cholesterol efflux [198]; anti-inflammatory properties of apoA-I [62] and HDL [222] HF HDL inflammatory index [239]; SAA content [239]; PON1 activity [218,239] efflux capacity [200] MetS TG content [203], S1P content [203], HDL-mediated eNOS activation [203]; anti-oxidative properties [240]; anti-apoptotic activity [206]; CE and TG content [206] Premature AMI HDL inflammatory index [220]; number of large HDL particles [220] CKD HDL2 and HDL3, LCAT and HL deficiency, CETP activity, TG and PL content, antioxidant and anti-inflammatory properties, RCT [224]; NO production [225] Autoimmune disease ...…”

Section: Discussionmentioning

confidence: 99%

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Biological Consequences of Dysfunctional HDL

Pirillo

Catapano

Norata

2019

CMC

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Epidemiological studies have suggested an inverse correlation between high density lipoprotein (HDL) cholesterol levels and the risk of cardiovascular disease. HDLs promote reverse cholesterol transport (RCT) and possess several putative atheroprotective functions, associated to the anti-inflammatory, anti-thrombotic and anti-oxidant properties as well as to the ability to support endothelial physiology. The assumption that increasing HDL-C levels would be beneficial on cardiovascular disease (CVD), however, has been questioned as, in most clinical trials, HDL-C-raising therapies did not result in improved cardiovascular outcomes. These findings, together with the observations from Mendelian randomization studies showing that polymorphisms mainly or solely associated with increased HDL-C levels did not decrease the risk of myocardial infarction, shift the focus from HDL-C levels toward HDL functional properties. Indeed, HDL from atherosclerotic patients not only exhibit impaired atheroprotective functions but also acquire pro-atherogenic properties and are referred to as "dysfunctional" HDL; this occurs even in the presence of normal or elevated HDL-C levels. Pharmacological approaches aimed at restoring HDL functions may therefore impact more significantly on CVD outcome than drugs used so far to increase HDL-C levels. Aims of this review is to discuss the pathological conditions leading to the formation of dysfunctional HDL and their role in atherosclerosis and beyond.

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Section: Discussionmentioning

confidence: 99%

“…. HDL modified in vitro as well as HDL isolated from patients with CAD, diabetes, metabolic syndrome, chronic kidney disease or acute coronary syndrome fail to stimulate endothelial eNOS-activating pathways and NO production [94,[202][203][204] (Table 1).…”

Section: Alterations Of Atheroprotective Properties Of Hdl In Cardiovmentioning

confidence: 99%

Biological Consequences of Dysfunctional HDL

Pirillo

Catapano

Norata

2019

CMC

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“…Ezetimibe did not affect the plasma concentration of high-density lipoprotein-a beneficial cholesterol with vasoprotective property of enhancing endothelial NO production through activation of eNOS. 72 Denimal et al 73 showed that this beneficial effect of high-density lipoprotein was impaired by the sphingosine-1-phosphate depletion of high-density lipoprotein in patients with metabolic syndrome. On the basis of the premise that targeting glucagon-like peptide (GLP)-1 could provide better treatment of diabetes mellitus via pleiotropic cardiovascular protective effects beyond glycemic control, many clinical trials of GLP-1-based therapies have been conducted with variable effects on cardiovascular outcomes, and others are ongoing.…”

Section: Novel Therapeutic and Diagnostic Targets Agents For Metabolimentioning

confidence: 99%

Endothelial Functions

Godo

Shimokawa

2017

ATVB

394

258

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e108T he endothelium plays important roles in modulating vascular tone by synthesizing and releasing an array of endothelium-derived relaxing factors, including vasodilator prostaglandins, NO, and endothelium-dependent hyperpolarization (EDH) factors, as well as endothelium-derived contracting factors.1,2 Such redundant mechanisms, like endogenous hyperglycemic hormones, are advantageous for ensuring proper maintenance of vascular tone under pathological conditions, where one of the vasoactive factor-mediated responses is compromised favoring a vasoconstrictor, prothrombotic, and proinflammatory state. Endothelial dysfunction is mainly caused by reduced production or action of endothelium-derived relaxing factors and could be an initial step toward cardiovascular disease.1 Indeed, evaluation of endothelial functions in humans has attracted much attention in the clinical settings because it serves as an excellent surrogate marker of cardiovascular events. For instance, endothelial dysfunction, as evaluated by impaired flow-mediated dilation of the brachial artery or digital reactive hyperemia index in peripheral arterial tonometry, is associated with future cardiovascular events in patients with coronary artery disease, 3-5 and 1-SD decrease in flow-mediated dilation or reactive hyperemia index is associated with doubling of cardiovascular event risk. 6 These observations suggest that endothelial function in peripheral vascular beds could predict future cardiovascular events.In this review, we will sum up the current advances and trends in the research on endothelial functions from bench to bedside with particular focus on recent publications in Arteriosclerosis, Thrombosis, and Vascular Biology. Earlier highlights of the journal on endothelial biology are extensively summarized in some review articles. 7-9 Emerging Modulators of Endothelial Functions Shear StressAs Lüscher and Corti 10 described in an editorial, flow is the signal of life. This physical force is sensed by the endothelium lining internal surface of the whole cardiovascular system to be translated into numerous downstream signaling pathways in a moment to moment manner in response to diverse physiological demands in the body. Indeed, shear stress is one of the important physiological cues that make endothelial cells synthesize and release endothelium-derived relaxing factors to cause relaxation of underlying vascular smooth muscle and vasodilatation. In this context, novel mechanisms of endothelial mechanotransduction in health and disease have been unveiled and summarized in a review series published recently in Arteriosclerosis, Thrombosis, and Vascular Biology. 11,12 Briefly, Zhou et al 12 emphasized the distinct roles of atheroprotective laminar or pulsatile shear stress versus atheroprone oscillatory shear stress or disturbed flow and discussed in detail the underlying molecular mechanisms that are dependent on these patterns of flow. Abe and Berk 11 further reviewed the current knowledge on the dual roles of shear stress with emphasis plac...

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“…Localization and activity of eNOS are affected by lipid enrichment and enhanced kinetic stimulation of protein kinase C-meditated phosphorylation of eNOS at S1177. 81,82 Shear stress-induced PKC-mediated phosphorylation of endothelial eNOS at S1177 is also affected by glycolysis-dependent purine signaling and autophagy, 83 indicating that eNOS stimulation occurs via multiple mechanisms. Where eNOS and vasodilator-stimulated phosphoprotein (VASP) – a PKG target – have been genetically deleted in mice, inflammatory cytokines, monocyte adhesion and macrophage infiltration have been observed in adipose tissue.…”

Section: Reactive Nitrogen Speciesmentioning

confidence: 99%

Redox Control of Vascular Function

Straub

2017

ATVB

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Impairment of the Ability of HDL From Patients With Metabolic Syndrome but Without Diabetes Mellitus to Activate eNOS

Cited by 49 publications

References 35 publications

Biological Consequences of Dysfunctional HDL

Biological Consequences of Dysfunctional HDL

Endothelial Functions

Redox Control of Vascular Function

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