Abstract 15299: Role of Leptin on Plaque Stability: Insights From the Opal (OPtimized management of Atherosclerosis in various Localizations) Carotid Endarterectomy Study
The link between leptin and carotid plaque stability remains unclear. In the present study, we investigated the potential link between leptin concentrations, as measured in serum and in plaque, and plaque phenotype in patients with carotid artery disease. One hundred and forty six consecutive patients scheduled for carotid endarterectomy were included in the OPAL study and underwent blood and plaque sampling. Plaque-related symptoms (recent history of stroke or transient ischemic attack) were recorded for each patient: 75 were classified as symptomatic and 71 as asymptomatic. Leptin was assessed in serum (9.70 [4.60-19.9] ng/mL) and plaques (0.075 [0.040-0.163] ng/mg protein). Plaque stability was assessed by collagen to macrophage ratio (1.86 [1.32-2.25]). The effect of leptin (0-100 ng/mL) on human vascular smooth muscle cells (VSMCs) proliferation and migration was investigated in cell culture. Leptin and its receptor were co-localized with plaque VSMCs by immunofluorescence. Serum and intra-plaque leptin levels were positively correlated to each other (p<0.001, r=0.73) and were significantly lower in symptomatic vs. asymptomatic patients (8.5 [4.2-13.9] vs 13.4 [5.9-28.6] ng/mL, p=0.0068; 0.059 [0.035-0.123] vs 0.104 [0.055-0.289] ng/mg protein, p=0.03; respectively). After adjustment for confounding risk factors (age, male sex, BMI, smoking, diabetes mellitus, arterial hypertension, dyslipidemia, statin and CRP), serum leptin level was independently and negatively associated with plaque-related symptoms (ß=-1.74; 95%CI [-3.381;-0.115]; p=0.03). Serum and intra-plaque leptin were strongly correlated with a high collagen to macrophage ratio (r=0.54, p=0.03; r=0.79, p=0.05; respectively). When human VSMCs were exposed in vitro to leptin at low concentrations (0 to 20 ng/ml) a strong signal of migration was observed, followed by a signal of proliferation at higher concentrations (20 to 100 ng/ml).
Conclusion: These results demonstrate, for the first time, that leptin is associated with plaque stability and could, via its migratory and proliferative effects on human VSMCs, play an active role in this process.
- © 2011 by American Heart Association, Inc.