HDL action on the vascular wall: is the answer NO?

Shaul, Philip W.; Mineo, Chieko

doi:10.1172/jci200421072

Cited by 46 publications

(22 citation statements)

References 31 publications

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“…32 Here, we show that HDL modified with HOCl concentrations that are easily achieved under acute inflammation 13,33 caused a marked, sustained, concentration-dependent, and timedependent decrease of NO production in stimulated HUVECs as measured by the conversion of L-arginine to L-citrulline ( Figure 1A to 1C). To confirm the functional significance of these findings, we assessed the effects of HOCl-HDL on the production of cGMP, a second messenger formed via activation of soluble guanylate cyclase by NO.…”

Section: Resultsmentioning

confidence: 62%

2-Chlorohexadecanal Derived From Hypochlorite-Modified High-Density Lipoprotein–Associated Plasmalogen Is a Natural Inhibitor of Endothelial Nitric Oxide Biosynthesis

Marsche

Heller

Fauler

et al. 2004

ATVB

104

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Objective-Myeloperoxidase, a heme enzyme that is present and active in human atherosclerotic lesions, provides a source for the generation of proinflammatory chlorinated reactants contributing to endothelial dysfunction. Modification of high-density lipoprotein (HDL) by hypochlorous acid/hypochlorite (HOCl/Oce Ϫ )-generated in vivo by the myeloperoxidase-hydrogen peroxide-chloride system of activated phagocytes-forms a proatherogenic lipoprotein particle that binds to and is internalized by endothelial cells. Methods and Results-Here we show that HDL, modified with physiologically relevant HOCl concentrations, attenuates the expression and activity of vasculoprotective endothelial nitric oxide synthase. HOCl-HDL promotes dislocalization of endothelial nitric oxide synthase from the plasma membrane and perinuclear location of human umbilical venous endothelial cells. We could identify 2-chlorohexadecanal as the active component mediating this inhibitory activity. This chlorinated fatty aldehyde is formed during HOCl-mediated oxidative cleavage of HDL-associated plasmalogen. Conclusion-2-Chlorohexadecanal, produced by the myeloperoxidase-hydrogen peroxide-chloride system of activated phagocytes may act as a mediator of vascular injury associated with ischemia-reperfusion injury, glomerulosclerosis, and atherosclerosis. Key Words: myeloperoxidase Ⅲ 2-chlorinated fatty aldehyde Ⅲ atherosclerosis Ⅲ modified lipids Ⅲ glomerulosclerosis Ⅲ neutrophils A nimal experimentation and clinical studies have provided convincing evidence that the known risk factors for cardiovascular disease can elicit a localized inflammatory response in the vasculature. The changes are most pronounced in endothelial cells and include oxidative stress, increased activation of endothelial signaling pathways, and the consequent adhesion, activation, and degranulation of leukocytes. The myeloperoxidase (MPO)-hydrogen peroxidesystem of stimulated leukocytes, primarily neutrophils, generates hypochlorous acid/hypochlorite (HOCl/Oce Ϫ ), a potent bacterial oxidant in vivo. 1 MPO and HOCl are emerging as critical modulators of vascular injury by promoting inflammatory arterial pathology and subsequent formation of mature plaques. MPO is present and active in human lesion material. 2 HOCl reacts with a wide range of biological substrates, including antioxidants, amines, sulfides, nucleotides, DNA, lipids, and (lipo)proteins. [3][4][5] HOCl-modified (lipo)proteins are present in human 6 -8 and rabbit lesions, 9,10 and disease stage-dependent accumulation of HOCl-modified (lipo)proteins has been reported. 7 Elevated levels of plasma high-density lipoprotein (HDL) protect against atherosclerotic vascular disease. A broad spectrum of potent antioxidant and anti-inflammatory activities has been ascribed to native HDL. 11,12 However, oxidation/modification by HOCl alters the physicochemical and metabolic properties of anti-atherogenic HDL. [13][14][15] In vivo, apolipoprotein A-I, the major apolipoprotein of HDL, represents a selective target for MPO-catalyz...

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Section: Resultsmentioning

confidence: 62%

2-Chlorohexadecanal Derived From Hypochlorite-Modified High-Density Lipoprotein–Associated Plasmalogen Is a Natural Inhibitor of Endothelial Nitric Oxide Biosynthesis

Marsche

Heller

Fauler

et al. 2004

ATVB

104

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“…The kinases involved include Akt (also known as protein kinase B), protein kinase A, protein kinase C, and calmodulin-dependent kinase II. 21 Previous reports showed that HDL stimulates the phosphorylation of eNOS at serine-1179, whereas HDL has no effect on the phosphorylation of threonine-497. HDL-induced phosphorylation of eNOS is mediated by Akt kinase, because the Effect of Ang II on HDL-mediated eNOS activation in HUVECs.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Scavenger Receptor Class BI Gene Expression by Angiotensin II in Vascular Endothelial Cells

Murao

Imachi

et al. 2007

Hypertension

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Abstract-High-density lipoprotein mediates a normal physiological process called reverse cholesterol transport. In this process, a scavenger receptor of the B class (SR-BI)/human homologue of SR-BI, CD36, and LIMPII analogous-1 (hSR-BI/CLA-1) facilitates the cellular uptake of cholesterol from high-density lipoprotein. 1,2 In this process, HDL particles shuttle cholesterol from extrahepatic tissues to the liver for further metabolism and excretion. 1 Enhanced reverse cholesterol transport lowers total body cholesterol and thereby reduces the risk of developing coronary artery disease. Thus, the plasma concentration of HDL is inversely related to the incidence of coronary artery disease. 3 The mouse scavenger receptor class BI (SR-BI) mediates selective uptake of HDL cholesterol ester into transfected Chinese hamster ovary cells. This finding provides an important link between a specific cell surface receptor and a pathway for the uptake of HDL. 4 Our previous reports show that human homologue of SR-BI, CD36, and LIMPII analogous-1 (hSR-BI/CLA-1), like mouse SR-BI, functions as a receptor for HDL. 5,6 However, the mechanisms by which HDL is atheroprotective are complex and not well understood.Endothelial dysfunction plays a pivotal role in the initiation and progression of atherosclerosis. In fact, the vascular endothelium modulates the vessel tone by releasing both relaxing and contractile factors, 7 regulates the adherence of mononuclear cells to its surface and the vascular permeability, 8,9 and produces substances involved in the regulation of hemostasis and tissue proliferation. 10 The release of NO by endothelial NO synthase (eNOS) is important in the regulation of cardiovascular homeostasis. Recent reports indicated that SR-BI and eNOS are colocalized in vascular endothelial cells. Thus, HDL activates eNOS via SR-BI, and the resulting

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“…We observed that in the aortas of theTie2 hABCA1 transgenic mice on a normal chow diet, but not the HFHC diet, there was increased expression of eNOS ( Fig. 6B ), which is known to have several anti-atherogenic effects ( 49,51 ). Caspase 6, Ripk1 [receptor (TNFRSF)-interacting serinethreoninekinase 1] and Tnfsf10 [tumor necrosis factor (ligand) superfamily, member 10] were found to be downregulated in the Tie2 hABCA1 transgenic mice ( Fig.…”

Section: Effect Of Hfhc Diet On Expression Of Habca1 and Endogenous Gmentioning

confidence: 94%

“…Besides the effect of HDL in promoting cholesterol effl ux, the increased HDL in the transgenic mice could also have reduced atherosclerosis by some of the other benefi cial properties of HDL ( 48 ). For example, HDL has been shown to reduce infl ammation by suppressing activation of NF-kappa B and also by decreasing the expression of adhesion proteins (48)(49)(50). We observed that in the aortas of theTie2 hABCA1 transgenic mice on a normal chow diet, but not the HFHC diet, there was increased expression of eNOS ( Fig.…”

Section: Effect Of Hfhc Diet On Expression Of Habca1 and Endogenous Gmentioning

confidence: 99%

Endothelial expression of human ABCA1 in mice increases plasma HDL cholesterol and reduces diet-induced atherosclerosis

Vaisman

Demosky

Stonik

et al. 2012

Journal of Lipid Research

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HDL action on the vascular wall: is the answer NO?

Cited by 46 publications

References 31 publications

2-Chlorohexadecanal Derived From Hypochlorite-Modified High-Density Lipoprotein–Associated Plasmalogen Is a Natural Inhibitor of Endothelial Nitric Oxide Biosynthesis

2-Chlorohexadecanal Derived From Hypochlorite-Modified High-Density Lipoprotein–Associated Plasmalogen Is a Natural Inhibitor of Endothelial Nitric Oxide Biosynthesis

Regulation of Scavenger Receptor Class BI Gene Expression by Angiotensin II in Vascular Endothelial Cells

Endothelial expression of human ABCA1 in mice increases plasma HDL cholesterol and reduces diet-induced atherosclerosis

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