Mohamed A Zayed1, Scott D Harring2, Dana R Abendschein3, Chandu Vemuri1, Dongsi Lu4, Lisa Detering2, Yongjian Liu2, Pamela K Woodard2. 1. 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. 2. Mallinckrodt Institute of Radiology, Washington University School of Medicine, USA. 3. Center for Cardiovascular Research, Department of Internal Medicine, Washington University School of Medicine, USA. 4. Department of Pathology and Immunology, Washington University School of Medicine, USA.
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). CONCLUSION: 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.
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 humancarotid 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). CONCLUSION: 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: S Chaturvedi; A Bruno; T Feasby; R Holloway; O Benavente; S N Cohen; R Cote; D Hess; J Saver; J D Spence; B Stern; J Wilterdink Journal: Neurology Date: 2005-09-27 Impact factor: 9.910
Authors: Brian Casserly; Jeffrey M Mazer; Alexander Vang; Elizabeth O Harrington; James R Klinger; Sharon Rounds; Gaurav Choudhary Journal: Life Sci Date: 2011-07-27 Impact factor: 5.037
Authors: K Doi; T Ikeda; H Itoh; K Ueyama; K Hosoda; Y Ogawa; J Yamashita; T H Chun; M Inoue; K Masatsugu; N Sawada; Y Fukunaga; T Saito; M Sone; K Yamahara; H Kook; M Komeda; M Ueda; K Nakao Journal: Arterioscler Thromb Vasc Biol Date: 2001-06 Impact factor: 8.311
Authors: Victor H Casco; John P Veinot; Mercedes L Kuroski de Bold; Roy G Masters; Michelle M Stevenson; Adolfo J de Bold Journal: J Histochem Cytochem Date: 2002-06 Impact factor: 2.479
Authors: Yang Gu; Donna Thompson; Jie Xu; David F Lewis; John A Morgan; Danielle B Cooper; Charles E McCathran; Yuping Wang Journal: Pregnancy Hypertens Date: 2017-12-07 Impact factor: 2.899
Authors: Auston Z Miller; Alexander Satchie; Alex P Tannenbaum; Aman Nihal; James A Thomson; David T Vereide Journal: Stem Cell Reports Date: 2018-01-09 Impact factor: 7.765