Apolipoprotein Signature of HDL and LDL from Atherosclerotic Patients in Relation with Carotid Plaque Typology: A Preliminary Report.

Francesco Finamore,Marilena Formato,Rita Spirito,Gabriele Nieddu,Anna Guarino,Antonio Junior Lepedda,Silvia Rocchiccioli

doi:10.3390/biomedicines9091156

Abstract

In the past years, it has become increasingly clear that the protein cargo of the different lipoprotein classes is largely responsible for carrying out their various functions, also in relation to pathological conditions, including atherosclerosis. Accordingly, detailed information about their apolipoprotein composition and structure may contribute to the revelation of their role in atherogenesis and the understanding of the mechanisms that lead to atherosclerotic degeneration and toward vulnerable plaque formation. With this aim, shotgun proteomics was applied to identify the apolipoprotein signatures of both high-density and low-density lipoproteins (HDL and LDL) plasma fractions purified from healthy volunteers and atherosclerotic patients with different plaque typologies who underwent carotid endarterectomy. By this approach, two proteins with potential implications in inflammatory, immune, and hemostatic pathways, namely, integrin beta-2 (P05107) and secretoglobin family 3A member 2 (Q96PL1), have been confirmed to belong to the HDL proteome. Similarly, the list of LDL-associated proteins has been enriched with 21 proteins involved in complement and coagulation cascades and the acute-phase response, which potentially double the protein species of LDL cargo. Moreover, differential expression analysis has shown protein signatures specific for patients with “hard” or “soft” plaques.

Highlights

Plaque rupture/erosion leading to atherothrombosis is the underlying pathology responsible for major acute events in cardiovascular disease, such as stroke, acute coronary syndrome, and peripheral artery occlusion [1,2]
It was shown that coronary artery disease (CAD) risk-lowering therapy with statin/niacin partially reverts the changes in HDL proteome observed in CAD subjects [24]
LDL and HDL fractions were purified from pooled plasma samples from patients undergoing carotid endarterectomy with either soft or hard plaques and from healthy normolipidemic volunteers

Summary

Introduction

Plaque rupture/erosion leading to atherothrombosis is the underlying pathology responsible for major acute events in cardiovascular disease, such as stroke, acute coronary syndrome, and peripheral artery occlusion [1,2]. In the past twenty years, with the improvement of proteomic tools, large-scale technologies have been applied to elucidate pathways of atherosclerotic degeneration and identify new circulating markers to be utilized either as early diagnostic traits or as targets for new drug therapies [5]. It is becoming increasingly clear that the HDL protein cargo, rather than HDL-cholesterol levels, is crucial for its vascular function, even turning HDL from anti-atherogenic to pro-atherogenic in cardiovascular disease [19,20,21,22] In this respect, we have evidence of increased levels of acute-phase serum amyloid A protein in HDL as well as VLDL and LDL plasma fractions purified from patients undergoing carotid endarterectomy [23]. It was shown that coronary artery disease (CAD) risk-lowering therapy with statin/niacin partially reverts the changes in HDL proteome observed in CAD subjects [24]

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