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181 Enrichment of Thrombin Activatable Fibrinolysis Inhibitor (TAFI), A Novel Pro-Thrombotic Protein in Lipoproteins of South Asian Patients with Coronary Artery Disease
  1. Sanjay Bhandari,
  2. Donald Jones,
  3. Leong Ng
  1. University of Leicester

Abstract

Introduction CAD is a leading cause of mortality in the UK with South Asians at heightened risk, owing to their disproportionately high prevalence of diabetes and metabolic syndrome. Simplistic notion of lipoprotein was transporters of lipids has been challenged, with a growing appreciation of their functionality, due to their carriage of low abundant proteins which are concerned with redox, inflammation and coagulation. In this study we sought to compare the lipoproteins and their associated protein cargoes between South Asian and Caucasian patients with CAD to further understand the differential risk that exists.

Methods South Asian males (n = 51, age mean ± SD 58 ± 8.6years) and Caucasian males (n = 49, age mean ± SD 64 ± 8.7years) with angiographic evidence of CAD were recruited, after fulfilling the inclusion criteria, into this single centre prospective cohort study. Blood was withdrawn from the consented patients. Lipoproteins and their associated proteins were isolated using a novel lipoaffinity resin. A bottom-up label-free unbiased lipoproteomic discovery workflow was utilised. Samples were analysed on a Waters G2S high definition ion mobility enabled mass spectrometer. Data analysis was executed using Progenesis Qi with a stringent FDR of 1%.

Results As expected South Asians were younger and had a higher prevalence of diabetes. Renal function, lipid parameters, burden of CAD and cardiovascular medication prescription were equivalent between the two ethnicities. 272 proteins were identified in both groups, of which 28 demonstrated significant differential expression (P < 0.05). South Asians were found to have enrichment of proteins concerned with acute inflammation (alpha-1 acid glycoprotein), complement activation (ficolin-2), extracellular remodelling (thrombospondin-1), endothelial dysfunction (profilin-1) and pro-thrombosis (thrombin activatable fibrinolysis inhibitor [TAFI]/carboxypeptidase B2) relative to Caucasians. South Asians had depletion of tetranectin, concerned with fibrinolysis, compared to their Caucasian counterparts. Biomarker verification revealed that plasma levels of TAFI were significantly higher in South Asian patients compared to Caucasian patients with CAD, using a single site in-house immunoassay (P = 0.045).

Conclusion CAD remodels the lipoproteins and their associated protein cargo with ethnic specific alterations, such that South Asian patients have a predominance of pro-inflammatory and pro-thrombotic proteins compared to Caucasian patients. Higher plasma levels of TAFI in the South Asian patients relative to the Caucasian patients, may contribute to a pro-thrombotic state and to their excess CAD risk.

  • Lipoproteins
  • Coronary artery disease
  • Proteomics

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