Leptin receptor is elevated in carotid plaques from neurologically symptomatic patients and positively correlated with augmented macrophage density

• Published in: Journal of vascular surgery 2008-11, Vol.48 (5), p.1146-1155
• Main Authors: Schneiderman, Jacob, MD, Simon, Amos J., PhD, Schroeter, Marco R., MD, Flugelman, Moshe Y., MD, Konstantinides, Stavros, MD, Schaefer, Katrin, MD
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; Biomarkers - analysis; Biomarkers - blood; C-Reactive Protein - analysis; Carotid Stenosis - complications; Carotid Stenosis - metabolism; Carotid Stenosis - pathology; Cerebrovascular Disorders - etiology; Cerebrovascular Disorders - metabolism; Cerebrovascular Disorders - pathology; Female; Humans; Immunohistochemistry; Interleukin-6 - blood; Leptin - blood; Macrophage-1 Antigen - analysis; Macrophage-1 Antigen - genetics; Macrophages - immunology; Macrophages - pathology; Male; Medical sciences; Middle Aged; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Neurology; Polymerase Chain Reaction; Protein Isoforms; Receptors, Leptin - analysis; Receptors, Leptin - blood; Receptors, Leptin - genetics; RNA, Messenger - analysis; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Up-Regulation; Vascular diseases and vascular malformations of the nervous system; Vascular Endothelial Growth Factor A - analysis; Vascular Endothelial Growth Factor A - genetics; Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels
• ISSN: 0741-5214; 1097-6809
• DOI: 10.1016/j.jvs.2008.06.054

Background Carotid artery lesions from symptomatic patients are characterized by inflammation and neovascularization. The adipokine leptin promotes angiogenesis and activates inflammatory cells, and the leptin receptor ( ob gene-encoded receptor), ObR, is expressed in advanced atherosclerotic lesions. The present study quantitatively analyzed ObR messenger RNA (mRNA) expression and immunoreactivity in carotid artery plaques from symptomatic and asymptomatic persons. Plaque angiogenesis, gene expression of vascular endothelial growth factor (VEGF), and macrophage density were also analyzed. Methods Carotid endarterectomy specimens were collected from 26 patients undergoing surgery for hemispheric cerebrovascular symptoms (n = 13) or progressive asymptomatic internal carotid stenosis (n = 13). A representative sample, including part of the most active site, was collected from each lesion and evaluated by real-time polymerase chain reaction analysis for ObR long and ObR common isoforms, VEGF 165 , and macrophage adhesion molecule-1 ( Mac-1) mRNA, and by immunohistochemistry for ObR, von Willebrand factor (vWF), and CD68 antigen expression. Results All plaques exhibited advanced atherosclerosis (American Heart Association class IV through VI). Transcript levels were preferentially elevated in symptomatic plaques for ObRlong ( P = .0006) and ObRcommon ( P = .033), with a simultaneous upregulation of VEGF165 ( P = .001) and Mac-1 mRNA expression ( P = .003). Immunohistochemical analysis confirmed a significant increase of ObR antigen levels ( P = .011) and CD68-positive inflammatory cells ( P = .049) in symptomatic plaques, whereas neovascularization, evident in all plaques, was similar in both groups ( P = .7). Conclusion The ObR long and ObR common genes are upregulated and their protein preferentially synthesized in clinically symptomatic carotid plaques. Moreover, ObR expression is positively correlated with augmentation of gene transcripts related to macrophage density and neovascularization. These data suggest that ObRlong and ObR common may be linked with histologic features of carotid plaque instability, which are associated with cerebral ischemic symptoms.