Abstract 591: Leptin receptor long Isoform is Increased and Positively Correlated with Augmented Macrophage Infiltration and Plaque Neovascularization in Carotid Plaques from Neurologically Symptomatic Patients
Objectives: Symptomatic carotid plaques are frequently characterized by increased inflammation and neovascularization. As leptin promotes plaque angiogenesis and activates inflammatory cells, and since the leptin receptor (ObR) antigen was demonstrated in advanced atherosclerotic plaques, we undertook a systematic analysis of carotid symptomatic and asymptomatic plaques, quantitatively assessing ObR mRNA expression and immunoreactivity. Moreover, parallel analyses of VEGF165, and Mac-1 transcript were performed, to account for plaque angiogenesis and macrophage density , respectively.
Methods: Carotid endarterectomy (CEA) plaques were collected from 26 patients undergoing surgery for hemispheric cerebro-vascular symptoms (13), or progressive asymptomatic internal carotid stenosis (13). A representative sample collected from each plaque was used in real-time quantitative (RQ) PCR analysis for ObRl (long), ObRc (common) isoforms, VEGF165, and Mac-1 transcripts. All plaques were classified histologically according to the AHA guidelines. Also, immunohistochemistry for von Willebrand factor (vWF) and ObR antigen were performed.
Results: All plaques exhibited advanced atherosclerosis, and AHA class V through VI were equally diagnosed in both groups. Interestingly, ObRl transcript levels were preferentially elevated in symptomatic plaques (P<0.03). A similar upregulation was demonstrated for VEGF165 (P<0.017), and Mac-1 (P<0.013). Immunohistochemical analyses also demonstrated that ObR antigen was significantly augmented in symptomatic plaques (P<0.05), and frequently colocalized with abundance of inflammatory cells. Neovascularization was evident in all plaques, and marginally increased in symptomatic plaques.
Conclusions: ObR-1 gene is preferentially upregulated, in clinically symptomatic carotid plaques, and positively correlated with simultaneous augmentation of VEGF165 and Mac-1 transcript. These data suggest that ObR-1 may be linked with histological features of plaque instability, like neovascularization and macrophage infiltration, shown to be associated with ischemic symptoms from carotid unstable plaques.