sLOX-1 May Predict Coronary Artery Disease in Patients with Psoriasis

Elizabeth M Florida, BASc

Credit: ResearchGate

High soluble extracellular domain of the receptor (sLOX‐1) and high-sensitivity C-reactive protein (CRP) levels increased the coronary plaque burden linked to atherosclerotic plaque progression, independent of biologic and systemic treatment, in patients with psoriasis, according to a study published in Journal of the American Heart Association.¹ Therefore, investigators theorized sLOX-1 could be a potential marker in estimating coronary artery disease risk in addition to common risk factors.

“Inflammation is a well‐established player in the pathogenesis of both psoriasis and coronary artery disease,” wrote lead investigator Elizabeth M Florida, BASc, research fellow at the National Heart, Lung, and Blood Institute, as well as the National Institutes of Health, and colleagues. “Increased levels of proinflammatory cytokines, such as tumor necrosis factor‐α, interleukin‐1β, and interleukin‐17, have been associated with psoriasis severity and shown to increase cellular expression of the LOX‐1 receptor for excessive oxidized low-density lipoprotein (oxLDL) uptake.”

LOX-1, which is highly expressed by endothelial cells during hyperlipidemia and chronic inflammatory conditions, is believed to induce disease progression by producing endothelial cell activation and dysfunction.² It also plays a role in creating atherosclerotic plaque rupture due to the induction of macrophage transformation into foam cells and proliferation of the vascular smooth muscle cell.

To better understand the relationship between inflammation, sLOX-1, and coronary plaque progression in this patient population, investigators measured the sLOX-1 levels of 327 patients with psoriasis who completed clinical, biochemical blood, and sLOX‐1 assessment at baseline, 1 year, and 4 years using an ELISA-based assay. Investigators hypothesized patients with elevated high-sensitivity CRP and sLOX-1 levels would exhibit an increased risk of coronary artery disease.

High-sensitivity CRP ≥4.0 mg/L was found in 81 patients who had coronary plaque phenotyping and were then followed longitudinally by coronary computed tomography angiography. Patients with high-sensitivity CRP were mostly men (54.3%), middle aged (51.47 years), and had moderate psoriasis disease severity (6.60 [interquartile range, 3.30 – 13.40]).

sLOX-1 was positively associated with high-risk coronary plaque features in patients with increased inflammation, which was was observed in noncalcified plaque burden (rho = .286; P = .02), fibro-fatty burden (rho = 0.346; P = .004), and necrotic burden (rho= .394; P = .002). Particularly, a link between sLOX-1 was strongly linked in fully adjusted models at both baseline and during the 1- and 4-year follow-up period regarding noncalcified burden (β = .19; P = .03), and fibro‐fatty burden (β = .29; P= .003). Coronary plaque features progressed over a 1-year period regardless of systemic or biologic treatment in this patient population with high sLOX-1.

Investigators noted the observational nature of the study as a limitation due to the potential for selection bias and confounders. Therefore, future research should focus on additional in vitro experiments and larger in vivo studies. Further, results may not be generalizable to all patients with psoriasis because of the small number of patients with elevated high-sensitivity CRP and moderate to severe psoriasis. Future studies including a larger cohort with a greater variety of disease may be beneficial.

“The reported data support the potential use of sLOX‐1 as a marker of coronary plaque progression as measured by coronary computed tomography angiography and for cardiovascular disease risk estimation in patients with chronic inflammatory conditions, including psoriasis,” investigators concluded.

References

1. ^{Florida EM, Li H, Hong CG, et al. Relationship of Soluble Lectin-Like Low-Density Lipoprotein Receptor-1 (sLOX-1) With Inflammation and Coronary Plaque Progression in Psoriasis [published online ahead of print, 2023 Nov 20]. J Am Heart Assoc. 2023;e031227. doi:10.1161/JAHA.123.031227}
2. ^{Kattoor AJ, Goel A, Mehta JL. LOX‐1: regulation, signaling and its role in atherosclerosis. Antioxidants (Basel). 2019; 8:8. doi: 10.3390/antiox8070218}