Roles of HDL function and sphingosine-1-phosphate in vasospastic angina

Abstract

Background: High-density lipoprotein cholesterol (HDL-C) levels are often reduced in patients with vasospastic angina (VSA), but the relevance of HDL functionality to VSA pathogenesis remains unclear. Cholesterol uptake capacity (CUC), a novel cell-free assay reflecting HDL-mediated cholesterol efflux, offers a practical measure of HDL functionality. In parallel, sphingosine-1-phosphate (S1P), an HDL-associated bioactive sphingolipid with vasoprotective properties, may also contribute to VSA. This study aimed to evaluate CUC and vasodilatory HDL components, including S1P, in patients with VSA.

Methods and results: Seventy-seven patients, comprising 53 patients who underwent an acetylcholine (Ach) provocation test (32 VSA at diagnosis and 21 non-VSA) and an additional 24 VSA outpatients were included. Patients with VSA had higher triglyceride levels compared with non-VSA patients, but HDL-C levels were not different. Further analysis revealed that CUC was lower in VSA patients at diagnosis compared with non-VSA patients. Serum levels of sphingosine-1-phosphate (S1P), a sphingolipid associated with HDL, were elevated in the VSA group (1.74 ± 0.76 vs. 1.31 ± 0.49 µM; p < 0.01). In the VSA outpatient and Non-VSA groups, S1P levels in crude analysis were significantly associated with VSA (OR = 3.14, 95 % CI: 1.25-7.88, p = 0.01). This association remained significant across all adjusted models (Models 1-4).

Conclusions: The present study found that CUC was a novel indicator of vasospasm-related HDL dysfunctionality and that S1P is a promising biomarker for treated patients with VSA. The cholesterol efflux pathway and sphingolipid metabolism could contribute to the etiology of vasospasm.

Study registration: This clinical study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000020942).

Keywords: Cholesterol uptake capacity (CUC); HDL function; High-density lipoprotein (HDL); Sphingosine-1-phosphate (S1P); Vasospastic angina (VSA).