title: Natriuretic Peptide Receptor-C is Up-Regulated in the Intima of Advanced Carotid Artery Atherosclerosis.
abstract: OBJECTIVE
  Natriuretic peptide receptor-C (NPR-C/NPR-3) is a cell surface protein involved in vascular remodelling that is up-regulated in atherosclerosis. NPR-C expression has not been well characterized in human carotid artery occlusive lesions. We hypothesized that NPR-C expression correlates with intimal features of vulnerable atherosclerotic carotid artery plaque.
  
  
  METHODS
  To test this hypothesis, we evaluated NPR-C expression by immunohistochemistry (IHC) in carotid endarterectomy (CEA) specimens isolated from 18 patients. The grade, location, and co-localization of NPR-C in CEA specimens were evaluated using two tissue analysis techniques.
  
  
  RESULTS
  Relative to minimally diseased CEA specimens, we observed avid NPR-C tissue staining in the intima of maximally diseased CEA specimens (65%; p=0.06). Specifically, maximally diseased CEA specimens demonstrated increased NPR-C expression in the superficial intima (61%, p=0.17), and deep intima (138% increase; p=0.05). In the superficial intima, NPR-C expression significantly co-localized with vascular smooth muscle cells (VSMCs) and macrophages. The intensity of NPR-C expression was also higher in the superficial intima plaque shoulder and cap regions, and significantly correlated with atheroma and fibroatheroma vulnerable plaque regions (β=1.04, 95% CI=0.46, 1.64).
  
  
  CONCLUSIONS
  These findings demonstrate significant NPR-C expression in the intima of advanced carotid artery plaques. Furthermore, NPR-C expression was higher in vulnerable carotid plaque intimal regions, and correlate with features of advanced disease. Our findings suggest that NPR-C may serve as a potential biomarker for carotid plaque vulnerability and progression, in patients with advanced carotid artery occlusive disease.
authors.affiliation: Department of Surgery, Section of Vascular Surgery, Washington University School of Medicine, USA and Department of Surgery, Veterans Affairs St. Louis Health Care System, USA.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Zayed
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Harring
authors.affiliation: Center for Cardiovascular Research, Department of Internal Medicine, Washington University School of Medicine, USA.
authors.forename: Dana R
authors.initials: DR
authors.lastname: Abendschein
authors.affiliation: Department of Surgery, Section of Vascular Surgery, Washington University School of Medicine, USA and Department of Surgery, Veterans Affairs St. Louis Health Care System, USA.
authors.forename: Chandu
authors.initials: C
authors.lastname: Vemuri
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, USA.
authors.forename: Dongsi
authors.initials: D
authors.lastname: Lu
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Detering
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, USA.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, USA.
authors.forename: Pamela K
authors.initials: PK
authors.lastname: Woodard
keywords: Arterial intima; Atherosclerosis; Carotid; Natriuretic peptide receptor-C; Plaque biomarker; Plaque vulnerability; Stroke