title: Sex differences in platelet toll-like receptors and their association with cardiovascular risk factors.
abstract: OBJECTIVE
  Platelets contribute to thrombosis, and platelet toll-like receptors (TLRs) are central in pathogen detection, potentially mediating infection-induced vascular occlusion. Using a large community-based cohort study, we sought to examine if platelets express all known TLR transcripts and analyze their association with cardiovascular risk factors.
  
  
  RESULTS
  mRNA levels for TLRs were measured in isolated platelets by high-throughput quantitative reverse transcriptase polymerase chain reaction in 1625 participants (mean age, 66.6±9; 54% women) of the Framingham Heart Study. We measured circulating inflammatory and thrombotic markers (C-reactive protein, interleukin-6, monocyte chemoattractant protein 1, intracellular cell adhesion molecule 1, soluble tumor necrosis factor-α receptor 1, and soluble p-selectin) and analyzed TLRs and their association with sex and cardiovascular risk factors by multivariable logit regression model adjusted for confounding factors. Platelets expressed all 10 TLR transcripts, and all TLRs were coexpressed. Women had higher platelet TLR expression, which associated with different cardiovascular risk factors, compared with men. In women, TLR1, TLR3, TLR6, and TLR7 were associated with body mass index and TLR5, TLR7, and TLR10 were associated with total cholesterol to high-density lipoprotein ratio. In men, TLR1, TLR2, and TLR3 were associated with lipid and TLR8 with hypertension treatment. Similarly, TLR expression in men was more commonly associated with circulating inflammatory markers (soluble tumor necrosis factor-α receptor 1 and intracellular cell adhesion molecule 1), whereas in women, TLR expression was associated with soluble p-selectin levels.
  
  
  CONCLUSIONS
  We report the first study to demonstrate that platelets express all TLR transcripts using a large community-based observational cohort. These transcripts are more abundant in women and have distinct associations with cardiovascular risk and inflammatory biomarkers that vary by sex.
authors: From the Division of Cardiovascular Medicine, Department of Medicine (M.K., E. Mikhalev, K.T., J.E.F.) and Department of Quantitative Health Sciences (E. Mick), University of Massachusetts Medical School, Worcester; Department of Medicine (E.J.B.) and Whitaker Cardiovascular Institute (E.J.B.), Boston University School of Medicine, MA; and NHLBI and Boston University's Framingham Heart Study, MA (E.J.B.). milka.koupenova@umassmed.edu.
authors: Milka
authors: M
authors: Koupenova
authors: From the Division of Cardiovascular Medicine, Department of Medicine (M.K., E. Mikhalev, K.T., J.E.F.) and Department of Quantitative Health Sciences (E. Mick), University of Massachusetts Medical School, Worcester; Department of Medicine (E.J.B.) and Whitaker Cardiovascular Institute (E.J.B.), Boston University School of Medicine, MA; and NHLBI and Boston University's Framingham Heart Study, MA (E.J.B.).
authors: Eric
authors: E
authors: Mick
authors: From the Division of Cardiovascular Medicine, Department of Medicine (M.K., E. Mikhalev, K.T., J.E.F.) and Department of Quantitative Health Sciences (E. Mick), University of Massachusetts Medical School, Worcester; Department of Medicine (E.J.B.) and Whitaker Cardiovascular Institute (E.J.B.), Boston University School of Medicine, MA; and NHLBI and Boston University's Framingham Heart Study, MA (E.J.B.).
authors: Ekaterina
authors: E
authors: Mikhalev
authors: From the Division of Cardiovascular Medicine, Department of Medicine (M.K., E. Mikhalev, K.T., J.E.F.) and Department of Quantitative Health Sciences (E. Mick), University of Massachusetts Medical School, Worcester; Department of Medicine (E.J.B.) and Whitaker Cardiovascular Institute (E.J.B.), Boston University School of Medicine, MA; and NHLBI and Boston University's Framingham Heart Study, MA (E.J.B.).
authors: Emelia J
authors: EJ
authors: Benjamin
authors: From the Division of Cardiovascular Medicine, Department of Medicine (M.K., E. Mikhalev, K.T., J.E.F.) and Department of Quantitative Health Sciences (E. Mick), University of Massachusetts Medical School, Worcester; Department of Medicine (E.J.B.) and Whitaker Cardiovascular Institute (E.J.B.), Boston University School of Medicine, MA; and NHLBI and Boston University's Framingham Heart Study, MA (E.J.B.).
authors: Kahraman
authors: K
authors: Tanriverdi
authors: From the Division of Cardiovascular Medicine, Department of Medicine (M.K., E. Mikhalev, K.T., J.E.F.) and Department of Quantitative Health Sciences (E. Mick), University of Massachusetts Medical School, Worcester; Department of Medicine (E.J.B.) and Whitaker Cardiovascular Institute (E.J.B.), Boston University School of Medicine, MA; and NHLBI and Boston University's Framingham Heart Study, MA (E.J.B.).
authors: Jane E
authors: JE
authors: Freedman
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000737:chemistry*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D026901:Membrane Transport Proteins / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D053594:Myeloid Differentiation Factor 88 / Q000097:blood / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012737:Sex Factors; D051193:Toll-Like Receptors / Q000097:blood* / Q000235:genetics
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; C507779:MYD88 protein, human; D026901:Membrane Transport Proteins; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D051193:Toll-Like Receptors; C454130:UNC93B1 protein, human
keywords: blood platelets; epidemiology; infection; inflammation
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