Inhibition of Arterial Thrombus Formation by ApoA1 Milano

Li, Dayuan; Weng, Sharon; Yang, Baichun; Zander, Dani S.; Saldeen, Tom; Nichols, Wilmer W.; Khan, Saeed R.; Mehta, Jawahar L.

doi:10.1161/01.atv.19.2.378

Cited by 139 publications

(105 citation statements)

References 38 publications

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“…Close to 2 decades ago, Li et al introduced the concept that apoA‐I Milano inhibits arterial thrombus formation through inhibition of thrombin activity,49 and recent data have shown an inhibitory effect of isolated human apoA‐I on human platelet activation and murine arterial/venous thrombosis 50. Recently, it has been shown that, in vivo, apoA‐I deficiency abrogates flow restriction–induced thrombosis in a mouse model of deep vein thrombosis, and intravenous human apoA‐I infusion in wild‐type mice decreases thrombi prevalence from 55% in vehicle‐infused mice to 0% 51.…”

Section: Resultsmentioning

confidence: 99%

Apolipoprotein A‐I Modulates Atherosclerosis Through Lymphatic Vessel‐Dependent Mechanisms in Mice

Milasan

Jean

Dallaire

et al. 2017

JAHA

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BackgroundSubcutaneously injected lipid‐free apoA‐I (apolipoprotein A‐I) reduces accumulation of lipid and immune cells within the aortic root of hypercholesterolemic mice without increasing high‐density lipoprotein–cholesterol concentrations. Lymphatic vessels are now recognized as prerequisite players in the modulation of cholesterol removal from the artery wall in experimental conditions of plaque regression, and particular attention has been brought to the role of the collecting lymphatic vessels in early atherosclerosis‐related lymphatic dysfunction. In the present study, we address whether and how preservation of collecting lymphatic function contributes to the protective effect of apoA‐I.Methods and ResultsAtherosclerotic Ldlr −/− mice treated with low‐dose lipid‐free apoA‐I showed enhanced lymphatic transport and abrogated collecting lymphatic vessel permeability in atherosclerotic Ldlr −/− mice when compared with albumin‐control mice. Treatment of human lymphatic endothelial cells with apoA‐I increased the adhesion of human platelets on lymphatic endothelial cells, in a bridge‐like manner, a mechanism that could strengthen endothelial cell–cell junctions and limit atherosclerosis‐associated collecting lymphatic vessel dysfunction. Experiments performed with blood platelets isolated from apoA‐I‐treated Ldlr −/− mice revealed that apoA‐I decreased ex vivo platelet aggregation. This suggests that in vivo apoA‐I treatment limits platelet thrombotic potential in blood while maintaining the platelet activity needed to sustain adequate lymphatic function.ConclusionsAltogether, we bring forward a new pleiotropic role for apoA‐I in lymphatic function and unveil new potential therapeutic targets for the prevention and treatment of atherosclerosis.

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Section: Resultsmentioning

confidence: 99%

Apolipoprotein A‐I Modulates Atherosclerosis Through Lymphatic Vessel‐Dependent Mechanisms in Mice

Milasan

Jean

Dallaire

et al. 2017

JAHA

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“…HDL has also been shown to exert antithrombotic effects by inhibiting platelet activation. The administration of reconstituted HDL to humans or the infusion of apoA-I Milano into rats inhibits platelet aggregation ( 176,192 ). HDL may regulate platelet function by downregulating the release of platelet-activating factor or by upregulating endothelial NO synthesis and release ( 185,193 ).…”

Section: Effects Of Hdl On Endothelial Thrombotic Activationmentioning

confidence: 99%

High density lipoproteins and endothelial functions: mechanistic insights and alterations in cardiovascular disease

Riwanto

Landmesser

2013

Journal of Lipid Research

141

123

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“…132 Intravenous injection of apoA-I Milano into rats resulted in significantly delayed time to thrombus formation and decreased thrombus weight. 144 …”

Section: Anti-inflammatory Effectsmentioning

confidence: 99%

High-Density Lipoproteins

Annema

Eckardstein

2013

Circ J

144

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Low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risks of coronary artery disease (CAD). HDL particles exert many effects in vitro and in vivo that may protect arteries from chemical or biological harm or facilitate repair of injuries. Nevertheless, HDL has not yet been successfully exploited for therapy. One potential reason for this shortfall is the structural and functional complexity of HDL particles, which carry more than 80 different proteins and more than 200 lipid species as well as several microRNAs and other potentially bioactive molecules. This physiological heterogeneity is further increased in several inflammatory conditions that increase cardiovascular risk, including CAD itself but also diabetes mellitus, chronic kidney disease, and rheumatic diseases. The quantitative and qualitative modifications of the proteome and lipidome, as well as the resulting loss of functions or gain of dysfunctions, are not recovered by the biomarker HDL-cholesterol. As yet the relative importance of the many physiological and pathological activities of normal and dysfunctional HDL, respectively, for the pathogenesis of atherosclerosis is unknown. The answer to this question, as well as detailed knowledge of structure-function-relationships of HDL-associated molecules, is a prerequisite to exploit HDL for the development of anti-atherogenic drugs as well as of diagnostic biomarkers for the identification, personalized treatment stratification, and monitoring of patients at increased cardiovascular risk. 2433Multifunctional but Vulnerable HDL munication of results. 15 As yet, clinical and epidemiological studies have come to discrepant and inconsistent conclusions on the prognostic performance of HDL subclasses differentiated by size. 14,20-24 Sometimes the associations of cardiovascular risk with the various HDL subclass concentrations were not stronger than with HDL-C, 20,21 and even if so, the associations with size were discrepant: significant associations with risk of cardiovascular events or stroke were found for small HDL in some studies, 22,23 but for medium-sized HDL 21,23 or large HDL 14,20,21,24 in others.Previous proteomic, lipidomic, and transcriptomic studies revealed a much greater structural complexity of HDLs: 80 different proteins, 25,26 more than 200 lipid species, 27,28 and several microRNAs 29,30 have been identified in HDL isolated from plasma by either ultracentrifugation, gel filtration, or immunoaffinity chromatography (Figure 1). Among the proteins, apoA-II is present in HDLs at the highest concentration after that of apoA-I and has been investigated for its cardiovascular risk association by several studies. In contrast to initial findings, large prospective studies did not find any significant differences in the risk association between apoA-II-containing and apoA-II-free HDL. [15][16][17] Despite their much lower concentrations relative to the 2 major proteins apoA-I and apoA-II and relative to the major lipids, many quantitatively minor componen...

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Inhibition of Arterial Thrombus Formation by ApoA1 Milano

Cited by 139 publications

References 38 publications

Apolipoprotein A‐I Modulates Atherosclerosis Through Lymphatic Vessel‐Dependent Mechanisms in Mice

Apolipoprotein A‐I Modulates Atherosclerosis Through Lymphatic Vessel‐Dependent Mechanisms in Mice

High density lipoproteins and endothelial functions: mechanistic insights and alterations in cardiovascular disease

High-Density Lipoproteins

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