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

Jacob Schneiderman*, Amos J. Simon, Marco R. Schroeter, Moshe Y. Flugelman, Stavros Konstantinides, Katrin Schaefer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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 ObRlong and ObRcommon isoforms, VEGF165, 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 ObRlong and ObRcommon 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 ObRcommon may be linked with histologic features of carotid plaque instability, which are associated with cerebral ischemic symptoms.

Original languageEnglish
Pages (from-to)1146-1155
Number of pages10
JournalJournal of Vascular Surgery
Issue number5
StatePublished - Nov 2008
Externally publishedYes


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