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Determinants of high-density lipoprotein (HDL) functions beyond proteome in Asian Indians: exploring the fatty acid profile of HDL phospholipids

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Abstract

Impaired high-density lipoprotein (HDL) functions are associated with development of coronary artery disease. In this study, we explored the quantitative differences in HDL (i.e. HDL proteome and fatty acid profile of HDL phospholipids) underlying the functional deficits associated with acute coronary syndrome (ACS). The relationship between HDL function and composition was assessed in 65 consecutive ACS patients and 40 healthy controls. Cholesterol efflux capacity (CEC) of HDL and lecithin cholesterol acyl transferase (LCAT) activity were significantly lower in patients with ACS compared to controls. In HDL proteome analysis, HDL isolated from ACS individuals was enriched in apolipoprotein C2 (inhibitor of LCAT), apolipoprotein C4 and serum amyloid A proteins and was deficient in apolipoprotein A-I and A-II. The fatty acid profile of HDL phospholipids analyzed using gas chromatography showed significantly lower percentages of stearic acid (17.4 ± 2.4 vs 15.8 ± 2.8, p = 0.004) and omega-3 fatty acids [eicosapentaenoic acid (1.0 (0.6–1.4) vs 0.7 (0.4–1.0), p = 0.009) and docosahexaenoic acid (1.5 ± 0.7 vs 1.3 ± 0.5, p = 0.03)] in ACS patients compared to controls. Lower percentages of these fatty acids in HDL were associated with higher odds of developing ACS. Our results suggest that distinct phospholipid fatty acid profiles found in HDL from ACS patients could be one of the contributing factors to the deranged HDL functions in these patients apart from the protein content and the inflammatory conditions.

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Data availability

The list of HDL associated proteins identified using mass spectrometry (ESM_1) and the normalised abundance values of the curated HDL associated proteins (ESM_2) used for analysis is included in the article as supplementary information. The raw mass spectrometry proteomics data have been deposited to the Proteome Xchange Consortium via the PRIDE partner repository with the data set identifier PXD014411.

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Acknowledgements

Young Scientist fellowship from Department of Health and Research, Ministry of Health and Family Welfare, Government of India, awarded to Himani Thakkar is gratefully acknowledged.

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No funding was received for conducting this study.

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Authors and Affiliations

  1. Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India

    Himani Thakkar, Vinnyfred Vincent, Ajay Kumar Gautam & Archna Singh

  2. Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India

    Ambuj Roy & Sandeep Singh

  3. Informatics and Big Data Unit, Council of Scientific and Industrial Research (CSIR), Institute of Genomics and Integrative Biology (IGIB), New Delhi, India

    Rintu Kutum

  4. Department of Cardiac Biochemistry, Cardiothoracic and Neurosciences Centre, All India Institute of Medical Sciences, New Delhi, India

    Lakshmy Ramakrishnan

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  1. Himani Thakkar
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by HT, VV, AKG and RK. The first draft of the manuscript was written by HT, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Archna Singh.

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The study was approved by the Institute Ethics Committee of All India Institute of Medical Sciences, New Delhi (Ethics committee reference number: IESC/T-380/17.10.2014) and certify that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

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Thakkar, H., Vincent, V., Roy, A. et al. Determinants of high-density lipoprotein (HDL) functions beyond proteome in Asian Indians: exploring the fatty acid profile of HDL phospholipids. Mol Cell Biochem 477, 559–570 (2022). https://doi.org/10.1007/s11010-021-04304-0

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