Institute for Pathophysiology, University Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany.
Basic Res Cardiol. 2010 Nov;105(6):821-32. doi: 10.1007/s00395-010-0112-5. Epub 2010 Jul 21.
High-density lipoproteins (HDL) are the major plasma carriers for sphingosine 1-phosphate (S1P) in healthy individuals, but their S1P content is unknown for patients with coronary artery disease (CAD). The aim of the study was to determine whether the S1P levels in plasma and HDL are altered in coronary artery disease. S1P was determined in plasma and HDL isolated by ultracentrifugation from patients with myocardial infarction (MI, n = 83), stable CAD (sCAD, n = 95), and controls (n = 85). In our study, total plasma S1P levels were lower in sCAD than in controls (305 vs. 350 pmol/mL). However, normalization to HDL-cholesterol (a known determinant of plasma S1P) revealed higher normalized plasma S1P levels in sCAD than in controls (725 vs. 542 pmol/mg) and even higher ones in MI (902 pmol/mg). The S1P amount contained in isolated HDL from these individuals was lower in sCAD than in controls (S1P per protein in HDL: 132 vs. 153 pmol/mg). The amount of total plasma S1P bound to HDL was lower in sCAD and MI than in controls (sCAD: 204, MI: 222, controls: 335 pmol/mL), while the non-HDL-bound S1P was, accordingly, higher (sCAD: 84, MI: 81, controls: 10 pmol/mL). HDL-bound plasma S1P was dependent on the plasma HDL-C in all groups, but normalization to HDL-C still yielded lower HDL-bound plasma S1P in patients with sCAD than in controls (465 vs. 523 pmol/mg). The ratio of non-HDL-bound plasma S1P to HDL-C-normalized HDL-bound S1P was also higher in both sCAD (0.18 mg/mL) and MI (0.15 mg/mL) than in controls (0.02 mg/mL). Remarkably, levels of non-HDL-bound plasma S1P correlated with the severity of CAD symptoms as graded by Canadian Cardiovascular Score, and discriminated patients with MI and sCAD from controls. Furthermore, a negative association was present between non-HDL-bound plasma S1P and the S1P content of isolated HDL in controls, but was absent in sCAD and MI. Finally, MI patients with symptom duration of less than 12 h had the highest levels of total and normalized plasma S1P, as well as the highest levels of S1P in isolated HDL. The HDL-C-normalized plasma level of S1P is increased in sCAD and even further in MI. This may be caused by an uptake defect of HDL for plasma S1P in CAD, and may represent a novel marker of HDL dysfunction.
高密度脂蛋白（HDL）是健康个体中鞘氨醇 1-磷酸（S1P）的主要血浆载体，但冠心病（CAD）患者的 HDL 中的 S1P 含量尚不清楚。本研究旨在确定 CAD 患者的血浆和 HDL 中的 S1P 水平是否发生改变。通过超速离心从心肌梗死（MI，n = 83）、稳定型 CAD（sCAD，n = 95）和对照组（n = 85）患者的血浆和 HDL 中分离出 S1P。在我们的研究中，sCAD 患者的总血浆 S1P 水平低于对照组（305 与 350 pmol/mL）。然而，与 HDL-胆固醇（已知的血浆 S1P 决定因素）标准化后，sCAD 患者的标准化血浆 S1P 水平高于对照组（725 与 542 pmol/mg），MI 患者的水平甚至更高（902 pmol/mg）。这些个体的分离 HDL 中所含的 S1P 量低于对照组（HDL 中每蛋白的 S1P：132 与 153 pmol/mg）。sCAD 和 MI 患者与对照组相比，总血浆 S1P 与 HDL 结合的量较低（sCAD：204，MI：222，对照组：335 pmol/mL），而非 HDL 结合的 S1P 相应较高（sCAD：84，MI：81，对照组：10 pmol/mL）。HDL 结合的血浆 S1P 在所有组中均依赖于血浆 HDL-C，但 sCAD 患者的 HDL-C 标准化的 HDL 结合的血浆 S1P 仍低于对照组（465 与 523 pmol/mg）。非 HDL 结合的血浆 S1P 与 HDL-C 标准化的 HDL 结合的血浆 S1P 比值在 sCAD（0.18 mg/mL）和 MI（0.15 mg/mL）中也高于对照组（0.02 mg/mL）。值得注意的是，非 HDL 结合的血浆 S1P 水平与加拿大心血管评分所评定的 CAD 症状严重程度相关，并将 MI 和 sCAD 患者与对照组区分开来。此外，在对照组中存在非 HDL 结合的血浆 S1P 与分离的 HDL 中的 S1P 含量之间存在负相关关系，但在 sCAD 和 MI 中不存在这种关系。最后，发病时间少于 12 h 的 MI 患者具有最高的总血浆和标准化 S1P 水平，以及分离的 HDL 中最高的 S1P 水平。sCAD 患者的 HDL-C 标准化血浆 S1P 水平升高，MI 患者的水平甚至更高。这可能是由于 CAD 患者的 HDL 对血浆 S1P 的摄取缺陷所致，可能是 HDL 功能障碍的一个新标志物。
