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Published on: March 15, 2022
Roles of HDL function and sphingosine-1-phosphate in vasospastic angina
Kei Sasaki1, Hirotaka Ezaki2, Yasuhiro Endo3
1Division of Anti-aging and Vascular Medicine, Department of Internal Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan.
Insights
This study reveals that reduced cholesterol uptake capacity (CUC) indicates dysfunctional high-density lipoprotein (HDL) in vasospastic angina (VSA). Elevated sphingosine-1-phosphate (S1P) levels are also linked to VSA, suggesting potential biomarkers.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Lipid Metabolism
Background:
- High-density lipoprotein cholesterol (HDL-C) is often reduced in vasospastic angina (VSA), but HDL functionality's role is unclear.
- Cholesterol uptake capacity (CUC) measures HDL functionality via cholesterol efflux.
- Sphingosine-1-phosphate (S1P), an HDL-associated lipid, has vasoprotective properties potentially relevant to VSA.
Purpose of the Study:
- To evaluate cholesterol uptake capacity (CUC) in patients with VSA.
- To assess serum levels of sphingosine-1-phosphate (S1P) in VSA patients.
- To explore the relationship between HDL functionality, S1P, and VSA pathogenesis.
Main Methods:
- Seventy-seven patients were included: 32 VSA, 21 non-VSA (undergoing acetylcholine provocation test), and 24 VSA outpatients.
- Cholesterol uptake capacity (CUC) was measured using a cell-free assay.
- Serum S1P levels were quantified and analyzed for association with VSA.
Main Results:
- VSA patients showed lower CUC compared to non-VSA patients.
- Serum S1P levels were significantly elevated in VSA patients (1.74 ± 0.76 µM vs. 1.31 ± 0.49 µM).
- Elevated S1P levels were significantly associated with VSA (OR = 3.14, p = 0.01), even after adjustment.
Conclusions:
- Reduced CUC is a novel indicator of HDL dysfunction in VSA.
- S1P is a promising biomarker for treated VSA patients.
- Cholesterol efflux pathways and sphingolipid metabolism may contribute to VSA etiology.
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).
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