What does HDL do? A new mechanism to slow atherogenesis – But a new problem in type 2 diabetes mellitus

Williams, Kevin Jon

doi:10.1016/j.atherosclerosis.2012.06.023

Cited by 9 publications

(6 citation statements)

References 36 publications

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“…42 The most widely accepted role of HDL is in promoting cholesterol efflux from foam cells, 42 but previous studies have indicated that HDL could also be atheroprotective by outcompeting LDL retention 30,31 or by blocking enzymatic modification of LDL. 43 However, HDL retention might also be unimportant for atherogenesis, as indicated by several Mendelian randomization studies of gene variants affecting HDL levels.…”

Section: Discussionmentioning

confidence: 99%

Disturbed Laminar Blood Flow Vastly Augments Lipoprotein Retention in the Artery Wall

Steffensen

Mortensen

Kjølby

et al. 2015

ATVB

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Objective— Atherosclerosis develops initially at branch points and in areas of high vessel curvature. Moreover, experiments in hypercholesterolemic mice have shown that the introduction of disturbed flow in straight, atherosclerosis-resistant arterial segments turns them highly atherosclerosis susceptible. Several biomechanical mechanisms have been proposed, but none has been demonstrated. In the present study, we examined whether a causal link exists between disturbed laminar flow and the ability of the arterial wall to retain lipoproteins. Approach and Results— Lipoprotein retention was detected at natural predilection sites of the murine thoracic aorta 18 hours after infusion of fluorescently labeled low-density lipoprotein. To test for causality between blood flow and the ability of these areas to retain lipoproteins, we manipulated blood flow in the straight segment of the common carotid artery using a constrictive collar. Disturbed laminar flow did not affect low-density lipoprotein influx, but increased the ability of the artery wall to bind low-density lipoprotein. Concordantly, disturbed laminar flow led to differential expression of genes associated with phenotypic modulation of vascular smooth muscle cells, increased expression of proteoglycan core proteins associated with lipoprotein retention, and of enzymes responsible for chondroitin sulfate glycosaminoglycan synthesis and sulfation. Conclusions— Blood flow regulates genes associated with vascular smooth muscle cell phenotypic modulation, as well as the expression and post-translational modification of lipoprotein-binding proteoglycan core proteins, and the introduction of disturbed laminar flow vastly augments the ability of a previously resistant, straight arterial segment to retain lipoproteins.

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Section: Discussionmentioning

confidence: 99%

Disturbed Laminar Blood Flow Vastly Augments Lipoprotein Retention in the Artery Wall

Steffensen

Mortensen

Kjølby

et al. 2015

ATVB

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“…In the context of the response-to-retention hypothesis, roles for HDL in every step have been hypothesized. (48) Those roles include interfering with the irreversible binding of plasma LDL to arterial wall proteoglycans (49)(50)(51), blocking SMase-induced aggregation of LDL (52,53), removing toxic lipids and resolving the maladaptive inflammatory infiltrate (54)(55)(56)(57)(58). Along these lines, the apoA-I mimetic peptide 4F was recently shown to block SMaseinduced LDL aggregation and the increase in binding of the modified LDL particles to human aortic proteoglycans.…”

Section: Lipoproteins Apolipoproteins and Atherosclerosismentioning

confidence: 99%

Advanced in Molecular Mechanisms of Atherosclerosis: From Lipids to Inflammation

2018

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BACKGROUND: Atherosclerosis is a leading cause of vascular disease worldwide. During the past several decades, landmark discoveries in the field of vascular biology have evolved our understanding of the biology of blood vessels and the pathobiology of local and systemic vascular disease states and have led to novel disease-modifying therapies for patients. This review is made to understand the molecular mechanism of atherosclerosis for these future therapies.CONTENT: Advances in molecular biology and -omics technologies have facilitated in vitro and in vivo studies which revealed that blood vessels regulate their own redox milieu, metabolism, mechanical environment, and phenotype, in part, through complex interactions between cellular components of the blood vessel wall and circulating factors. Dysregulation of these carefully orchestrated homeostatic interactions has also been implicated as the mechanism by which risk factors for cardiopulmonary vascular disease lead to vascular dysfunction, structural remodeling and, ultimately, adverse clinical events.SUMMARY: Atherosclerosis is a heterogeneous disease, despite a common initiating event of apoB-lipoproteins. Despite of acute thrombotic complications, an adequate resolution response is mounted, where efferocytosis prevents plaque necrosis and a reparative scarring response (the fibrous cap) prevents plaque disruption. However, a small percentage of developing atherosclerotic lesions cannot maintain an adequate resolution response, which leading to the formation of clinically dangerous plaques that can trigger acute lumenal thrombosis and tissue ischemiaand infarction.KEYWORDS: atherosclerosis, oxidative stress, inflammation, efferocytosis, foam cells, thrombosis

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“…L-amino acids are less toxic in the circulation however they are not resistant to enzymatic degradation via oral administration. Both have been used previously in biological studies with reported potent anti-inflammatory and antioxidant effects [7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein-AI mimetic peptides D-4F and L-5F decrease hepatic inflammation and increase insulin sensitivity in C57BL/6 mice

McGrath

Twigg

et al. 2020

PLoS ONE

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Background Apolipoprotein-AI (apo-AI) is the major apolipoprotein found in high density lipoprotein particles (HDLs). We previously demonstrated that apo-AI injected directly into high-fat diet fed mice improved insulin sensitivity associated with decreased hepatic inflammation. While our data provides compelling proof of concept, apoA-I mimetic peptides are more clinically feasible. The aim of this study was to test whether apo-AI mimetic peptide (D-4F and L-5F) treatment will emulate the effects of full-length apo-AI to improve insulin sensitivity.

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What does HDL do? A new mechanism to slow atherogenesis – But a new problem in type 2 diabetes mellitus

Cited by 9 publications

References 36 publications

Disturbed Laminar Blood Flow Vastly Augments Lipoprotein Retention in the Artery Wall

Disturbed Laminar Blood Flow Vastly Augments Lipoprotein Retention in the Artery Wall

Advanced in Molecular Mechanisms of Atherosclerosis: From Lipids to Inflammation

Apolipoprotein-AI mimetic peptides D-4F and L-5F decrease hepatic inflammation and increase insulin sensitivity in C57BL/6 mice

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