Triglyceride-rich lipoprotein sphingolipids are altered in primary hypertension: A pilot case-control study

BACKGROUND: Sphingolipids modulate vascular function and alterations in plasma sphingolipid profiles have been associated with hypertension. Plasma sphingolipids, such as ceramides (Cer) and sphingosine-1-phosphate (S1P), are predominantly carried by lipoproteins.

OBJECTIVE: We compared sphingolipid profiles in plasma and isolated lipoproteins of patients with primary hypertension with those of normotensive controls.

METHODS: Blood was obtained from 19 patients with hypertension and 19 age- and sex-matched normotensive controls. S1P and the 7 most abundant Cer were quantified by liquid chromatography-tandem mass spectrometry in plasma and in lipoproteins.

RESULTS: Total plasma Cer were significantly higher in patients with hypertension compared to controls (14.3 ± 1.0 vs 11.9 ± 0.7 µM; P = .047), while there were no differences in plasma S1P levels (1.8 ± 0.1 vs 2.1 ± 0.1 µM; P = .128). Total Cer carried by patient triglyceride-rich lipoproteins (TRL; ie, predominantly very low-density lipoproteins) were also significantly higher (1.33 ± 0.15 vs 0.58 ± 0.10 µM; P = .001), which held for all Cer tested. Systolic blood pressure positively correlated with plasma levels of Cer(d18:1/20:0) and Cer(d18:1/24:1), and diastolic blood pressure positively correlated with total Cer, Cer(d18:1/18:0), Cer(d18:1/20:0) and Cer(d18:1/24:0). Relative to plasma Cer(d18:1/24:0), levels of Cer(d18:1/18:0), Cer(d18:1/20:0) and Cer(d18:1/24:1) were significantly higher in patients with hypertension than in controls.

CONCLUSION: Patients with hypertension display higher plasma Cer levels than normotensive controls, which is mainly explained by elevated concentrations in TRLs. Cer levels positively correlate with systolic and diastolic blood pressure, and ratios of Cer relative to Cer(d18:1/24:0) suggest an increased cardiovascular risk.