title: Plasma Levels of Endothelial Microparticles Bearing Monomeric C-reactive Protein are Increased in Peripheral Artery Disease.
abstract: C-reactive protein (CRP) as an indicator of cardiovascular disease (CVD) has shown limited sensitivity. We demonstrate that two isoforms of CRP (pentameric, pCRP and monomeric, mCRP) present in soluble form or on microparticles (MPs) have different biological effects and are not all measured by clinical CRP assays. The high-sensitivity CRP assay (hsCRP) did not measure pCRP or mCRP on MPs, whereas flow cytometry did. MPs derived from endothelial cells, particularly those bearing mCRP, were elevated in peripheral artery disease (PAD) patients compared to controls. The numbers of mCRP(+) endothelial MPs did not correlate with hsCRP measurements of soluble pCRP, indicating their independent modulation. In controls, statins lowered mCRP(+) endothelial MPs. In a model of vascular inflammation, mCRP induced endothelial shedding of MPs and was proinflammatory, while pCRP was anti-inflammatory. mCRP on endothelial MPs may be both an unmeasured indicator of, and an amplifier of, vascular disease, and its detection might improve risk sensitivity.
authors.affiliation: The Division of Cardiovascular Sciences and the DeBakey Heart Center, Department of Medicine, Baylor College of Medicine and Houston Methodist Hospital, One Baylor Plaza, M.S. BCM620, Houston, TX, 77030, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Crawford
authors.affiliation: The Division of Cardiovascular Sciences and the DeBakey Heart Center, Department of Medicine, Baylor College of Medicine and Houston Methodist Hospital, One Baylor Plaza, M.S. BCM620, Houston, TX, 77030, USA. jtrial@bcm.edu.
authors.forename: JoAnn
authors.initials: J
authors.lastname: Trial
authors.affiliation: The Division of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.|The Division of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.|Center for Cardiovascular Prevention, Methodist DeBakey Heart and Vascular Center, 6565 Fannin St., Houston, TX, 77030, USA.
authors.forename: Vijay
authors.initials: V
authors.lastname: Nambi
authors.affiliation: The Division of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Ron C
authors.initials: RC
authors.lastname: Hoogeveen
authors.affiliation: The Division of Cardiovascular Sciences and the DeBakey Heart Center, Department of Medicine, Baylor College of Medicine and Houston Methodist Hospital, One Baylor Plaza, M.S. BCM620, Houston, TX, 77030, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Taffet
authors.affiliation: The Division of Cardiovascular Sciences and the DeBakey Heart Center, Department of Medicine, Baylor College of Medicine and Houston Methodist Hospital, One Baylor Plaza, M.S. BCM620, Houston, TX, 77030, USA.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Entman
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D010865:Pilot Projects; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D002097:C-Reactive Protein
keywords: CRP; Inflammation; Microparticle; Monomeric CRP; Pentameric CRP; Peripheral artery disease; hsCRP