title: Soluble sortilin is released by activated platelets and its circulating levels are associated with cardiovascular risk factors.
abstract: 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.
authors.affiliation: Advanced Medical Technology and Development Division, BML Inc., Saitama 350-1101, Japan. Electronic address: ogawa-k@bml.co.jp.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Advanced Medical Technology and Development Division, BML Inc., Saitama 350-1101, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Iwasaki
authors.affiliation: Advanced Medical Technology and Development Division, BML Inc., Saitama 350-1101, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kujiraoka
authors.affiliation: Advanced Medical Technology and Development Division, BML Inc., Saitama 350-1101, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Ishihara
authors.affiliation: Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kunimoto
authors.affiliation: Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Tadateru
authors.initials: T
authors.lastname: Takayama
authors.affiliation: Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanai
authors.affiliation: Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirayama
authors.affiliation: Advanced Medical Technology and Development Division, BML Inc., Saitama 350-1101, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hattori
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000097:blood* / Q000502:physiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage; D001792:Blood Platelets / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D016466:CHO Cells; D002319:Cardiovascular System / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000097:blood*; D003412:Cricetulus; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010949:Plasma / Q000378:metabolism; D015539:Platelet Activation; D010974:Platelet Aggregation; D011994:Recombinant Proteins / Q000378:metabolism; D012307:Risk Factors; D055815:Young Adult; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D001241:Aspirin; D002097:C-Reactive Protein; D011994:Recombinant Proteins; D000099183:Sortilin
keywords: Circulating plasma factor; Coronary artery disease; Platelet activation; Risk factors; Sortilin