Serum Soluble Lectin-like Oxidized Low-Density Lipoprotein Receptor-1 (sLOX-1) Is Associated with Atherosclerosis Severity in Coronary Artery Disease

Katharine A Kott; Elijah Genetzakis; Michael P Gray; Peter Hansen; Helen M McGuire; Jean Y Yang; Stuart M Grieve; Stephen T Vernon; Gemma A Figtree

doi:10.3390/biom13081187

Serum Soluble Lectin-like Oxidized Low-Density Lipoprotein Receptor-1 (sLOX-1) Is Associated with Atherosclerosis Severity in Coronary Artery Disease

Biomolecules. 2023 Jul 29;13(8):1187. doi: 10.3390/biom13081187.

Authors

Katharine A Kott^{1

2}, Elijah Genetzakis¹, Michael P Gray^{1

2}, Peter Hansen², Helen M McGuire^{3

4}, Jean Y Yang⁵, Stuart M Grieve^{6

7}, Stephen T Vernon^{1

2}, Gemma A Figtree^{1

2}

Affiliations

¹ Cardiovascular Discovery Group, Kolling Institute of Medical Research, University of Sydney, St Leonards, NSW 2065, Australia.
² Department of Cardiology, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
³ School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2006, Australia.
⁴ Ramaciotti Facility for Human Systems Biology, University of Sydney, Camperdown, NSW 2006, Australia.
⁵ School of Mathematics and Statistics, University of Sydney, Camperdown, NSW 2006, Australia.
⁶ Imaging and Phenotyping Laboratory, Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2006, Australia.
⁷ Department of Radiology, Royal Prince Alfred Hospital, Camperdown, NSW 2006, Australia.

Abstract

Risk-factor-based scoring systems for atherosclerotic coronary artery disease (CAD) remain concerningly inaccurate at the level of the individual and would benefit from the addition of biomarkers that correlate with atherosclerosis burden directly. We hypothesized that serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) would be independently associated with CAD and investigated this in the BioHEART study using 968 participants with CT coronary angiograms, which were scored for disease burden in the form of coronary artery calcium scores (CACS), Gensini scores, and a semi-quantitative soft-plaque score (SPS). Serum sLOX-1 was assessed by ELISA and was incorporated into regression models for disease severity and incidence. We demonstrate that sLOX-1 is associated with an improvement in the prediction of CAD severity when scored by Gensini or SPS, but not CACS. sLOX-1 also significantly improved the prediction of the incidence of obstructive CAD, defined as stenosis in any vessel >75%. The predictive value of sLOX-1 was significantly greater in the subgroup of patients who did not have any of the standard modifiable cardiovascular risk factors (SMuRFs). sLOX-1 is associated with CAD severity and is the first biomarker shown to have utility for risk prediction in the SMuRFless population.

Keywords: atherosclerosis; biomarker; computed tomography coronary angiography (CTCA); coronary artery disease (CAD); soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arteries
Atherosclerosis*
Coronary Angiography
Coronary Artery Disease* / diagnosis
Humans
Scavenger Receptors, Class E

Substances

Scavenger Receptors, Class E

Grants and funding

KAK is supported by an Australian Commonwealth Government Research Training Program Stipend Scholarship. STV is supported by a University of Sydney Postgraduate Research Scholarship funded by Heart Research Australia. SMG acknowledges the support of the NHMRC, Parker-Hughes Bequest, the New South Wales Office of Health and Medical Research and the Frecker Family. GAF is supported by a National Health and Medical Research Council Practitioner Fellowship (grant number APP11359290), Heart Research Australia, and the New South Wales Office of Health and Medical Research. The BioHEART study has received support from a combination of grants including from the Ramsay Teaching and Research Foundation, BioPlatforms Australia, the Vonwiller Foundation and Heart Research Australia.