Ogawa Kazuyuki, Ueno Takahiro, Iwasaki Tadao, Kujiraoka Takeshi, Ishihara Mitsuaki, Kunimoto Satoshi, Takayama Tadateru, Kanai Takashi, Hirayama Atsushi, Hattori Hiroaki
Advanced Medical Technology and Development Division, BML Inc., Saitama 350-1101, Japan.
Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan.
Atherosclerosis. 2016 Jun;249:110-5. doi: 10.1016/j.atherosclerosis.2016.03.041. Epub 2016 Apr 1.
Sortilin is involved multilaterally in the development of atherosclerosis. Here, we examine the release of soluble sortilin (sSortilin) from platelets and assess the association between circulating levels of sSoritlin and atherothrombosis such as coronary artery disease (CAD).
sSortilin levels measured in healthy subjects were higher in serum than in plasma (38.4 ± 8.7 vs. 15.8 ± 2.9 ng/mL; p < 0.0001). Platelets were shown to contain both membrane-bound sortilin and its soluble form lacking the cytoplasmic tail. Stimulation of platelet-rich plasma with collagen induced sSortilin release concomitantly with platelet aggregation, and the release was suppressed by aspirin. In clinical evaluation, plasma sSortilin was detected at significantly higher levels in cardiovascular risk patients with hypertension, dyslipidemia, and/or diabetes without CAD (non-CAD, 18.7 ± 3.3 ng/mL) than in patients with CAD under aspirin therapy (17.1 ± 3.6 ng/mL; p < 0.01) or in healthy controls (16.8 ± 2.9 ng/mL; p < 0.01). In these patients, plasma sSortilin levels were significantly correlated with platelet counts (rs = 0.33; p = 0.0085) and showed significant positive associations with cardiovascular risk factors: low-density lipoprotein cholesterol (rs = 0.37; p = 0.0023), triglycerides (rs = 0.28; p = 0.023), and serum uric acid (rs = 0.30; p = 0.017) in non-CAD, and γ-glutamyltransferase (rs = 0.43; p = 0.020) and high-sensitivity C-reactive protein (rs = 0.33, p = 0.0022) in CAD.
Elevated plasma sSortilin levels may be associated with in vivo platelet activation and could be a risk factor for atherothrombosis.
sortilin在动脉粥样硬化的发展过程中具有多方面的作用。在此，我们研究血小板中可溶性sortilin（sSortilin）的释放情况，并评估循环中sSoritlin水平与动脉粥样硬化血栓形成（如冠状动脉疾病（CAD））之间的关联。
健康受试者血清中的sSortilin水平高于血浆（38.4±8.7对15.8±2.9 ng/mL；p<0.0001）。血小板中既含有膜结合型sortilin，也含有缺乏细胞质尾的可溶性形式。用胶原蛋白刺激富含血小板的血浆会诱导sSortilin释放，同时伴随着血小板聚集，而阿司匹林可抑制这种释放。在临床评估中，未患CAD的高血压、血脂异常和/或糖尿病心血管风险患者（非CAD，18.7±3.3 ng/mL）血浆中sSortilin的检测水平显著高于接受阿司匹林治疗的CAD患者（17.1±3.6 ng/mL；p<0.01）或健康对照者（16.8±2.9 ng/mL；p<0.01）。在这些患者中，血浆sSortilin水平与血小板计数显著相关（rs=0.33；p=0.0085），并且与心血管风险因素呈显著正相关：在非CAD患者中与低密度脂蛋白胆固醇（rs=0.37；p=0.0023）、甘油三酯（rs=0.28；p=0.023）和血清尿酸（rs=0.30；p=0.由017）相关，在CAD患者中与γ-谷氨酰转移酶（rs=0.43；p=0.020）和高敏C反应蛋白（rs=0.33，p=0.0022）相关。
血浆sSortilin水平升高可能与体内血小板活化有关，并且可能是动脉粥样硬化血栓形成的一个风险因素。
