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. 2023 Jul 29;13(8):1187.
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

Katharine A Kott  1   2 , Elijah Genetzakis  1 , Michael P Gray  1   2 , Peter Hansen  2 , Helen M McGuire  3   4 , Jean Y Yang  5 , Stuart M Grieve  6   7 , Stephen T Vernon  1   2 , Gemma A Figtree  1   2
Affiliations

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

Katharine A Kott et al. Biomolecules. .

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).

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Conflict of interest statement

GAF reports personal consulting fees from CSL and grants from Abbott Diagnostic unrelated to the submitted work. In addition, GAF has a patent for Biomarkers and Oxidative Stress awarded, USA May 2017 (US9638699B2), issued to Northern Sydney Local Health District. The other authors have no disclosures. The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Study design for sLOX-1 biomarker analysis in the BioHEART biobank.
Figure 2
Figure 2
CAD scoring systems used to assess disease burden.
Figure 3
Figure 3
Scatter bar graphs of serum sLOX-1 levels of the 968 patients in the CTCA cohort by disease phenotype subgroup, with comparison to ACS as a positive control. ACS: acute coronary syndrome; sLOX-1: soluble lectin-like oxidized low-density lipoprotein receptor-1. **** p < 0.001, ns = not significant.
Figure 4
Figure 4
Comparison of model R2 values for multi-variable linear regression models, showing differences between models using risk factors (age, sex, body mass index, hypertension, hyperlipidemia, diabetes mellitus, significant smoking history, and significant family history of ischemic heart disease) and models using risk factors plus serum sLOX-1 values; SMuRFless subgroup analysis shown in blue shades. CACS: coronary artery calcium score; SPS: soft-plaque score; sLOX-1: soluble lectin-like oxidized low-density lipoprotein receptor-1. * p < 0.05, ** p < 0.01, *** p < 0.001, ns = not significant.
Figure 5
Figure 5
Odds ratios for the incidence of disease for all patients in the CTCA cohort as defined by the presence of any CAD (Gensini score > 0, blue), moderately obstructive CAD (stenosis in any vessel > 50%, green), or severely obstructive CAD (stenosis in any vessel > 75%, black) from multivariable logistic regression models.
Figure 6
Figure 6
Bivariate correlations between sLOX-1 and the three disease scores: CACS, Gensini, and SPS, for all patients (top panel) and SMuRFless patients (bottom panel). CACS: coronary artery calcium score; SPS: soft-plaque score; sLOX-1: soluble lectin-like oxidized low-density lipoprotein receptor-1.
Figure 7
Figure 7
Scatter bar graphs demonstrating significant differences in serum sLOX-1 levels in those with a history of (A) peripheral arterial disease or (B) a significant smoking history in the CTCA cohort, and (C) scatter plot of sLOX-1 vs. age, with trend line demonstrating the bivariate correlation between sLOX-1 and age. * p < 0.05.
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