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Review
. 2022 Feb 21;118(3):716-731.
doi: 10.1093/cvr/cvab017.

Relationship between lipoproteins, thrombosis, and atrial fibrillation

Wern Yew Ding  1 , Majd B Protty  2 , Ian G Davies  3 , Gregory Y H Lip  1   4
Affiliations
Review

Relationship between lipoproteins, thrombosis, and atrial fibrillation

Wern Yew Ding et al. Cardiovasc Res. .

Abstract

The prothrombotic state in atrial fibrillation (AF) occurs as a result of multifaceted interactions, known as Virchow's triad of hypercoagulability, structural abnormalities, and blood stasis. More recently, there is emerging evidence that lipoproteins are implicated in this process, beyond their traditional role in atherosclerosis. In this review, we provide an overview of the various lipoproteins and explore the association between lipoproteins and AF, the effects of lipoproteins on haemostasis, and the potential contribution of lipoproteins to thrombogenesis in AF. There are several types of lipoproteins based on size, lipid composition, and apolipoprotein category, namely: chylomicrons, very low-density lipoprotein, low-density lipoprotein (LDL), intermediate-density lipoprotein, and high-density lipoprotein. Each of these lipoproteins may contain numerous lipid species and proteins with a variety of different functions. Furthermore, the lipoprotein particles may be oxidized causing an alteration in their structure and content. Of note, there is a paradoxical inverse relationship between total cholesterol and LDL cholesterol (LDL-C) levels, and incident AF. The mechanism by which this occurs may be related to the stabilizing effect of cholesterol on myocardial membranes, along with its role in inflammation. Overall, specific lipoproteins may interact with haemostatic pathways to promote excess platelet activation and thrombin generation, as well as inhibiting fibrinolysis. In this regard, LDL-C has been shown to be an independent risk factor for thromboembolic events in AF. The complex relationship between lipoproteins, thrombosis and AF warrants further research with an aim to improve our knowledge base and contribute to our overall understanding of lipoprotein-mediated thrombosis.

Keywords: Atrial fibrillation; Haemostasis; High-density lipoprotein; Incidence; Lipids; Lipoprotein(a); Lipoproteins; Low-density lipoprotein; Oxidized lipoprotein; Stroke; Thromboembolism; Thrombosis; Very low-density lipoprotein.

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Figures

Figure 1
Figure 1
Representative schematic of lipid subtypes. Example structures from each LIPID MAPS category of lipids are shown in this figure highlighting their structural features. Fatty acids (FA), which may be saturated or unsaturated, form the basic building blocks of lipids, with each class having specific defining feature. Chemical structures are from PubChem and LIPID MAPS.
Figure 2
Figure 2
Lipoprotein types and structures. Representative description of typical diameter, content and apolipoprotein constituents of different lipoprotein classes. Created using Biorender.com. ApoB-100, apolipoprotein B100; CE, cholesterol ester; GPL, glycerophospholipids; HDL, high-density lipoprotein; IDL, intermediate-density lipoprotein; LDL, low-density lipoprotein; Lp(a), lipoprotein(a); TG, triglycerides; VLDL, very low-density lipoprotein.
Figure 3
Figure 3
Effects of lipoproteins on haemostasis. Created using Biorender.com. HDL, high-density lipoprotein; LDL, low-density lipoprotein; Lp(a), lipoprotein(a); PAI-1, plasminogen activator inhibitor-1; TF, tissue factor; TG, triglycerides; tPA, tissue plasminogen activator; VLDL, very low-density lipoprotein.
Figure 4
Figure 4
Pathogenic role of VLDL in metabolic syndrome-related atrial cardiomyopathy. Created using Biorender.com. MetS, metabolic syndrome; NFAT, nuclear factor of activated T cells; SOCE, store-operated calcium entry; VLDL, very low-density lipoprotein.
See this image and copyright information in PMC

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