Atherosclerosis is a chronic fibro-proliferative and immuno-inflammatory artery disease characterized by the endothelial dysfunction, local oxidation of circulating lipoproteins, their accumulation in the vascular wall and activation of proinflammatory cytokine genes. Clinical presentation of atherosclerosis is initiated by plaque destabilization due to a local inflammatory process. EL is a new member of triglyceride lipase gene family which is likely to have an important role in plaque destabilization by way of local inflammation. EL expression is increased under the influence of proinflammatory cytokines, oxidized LDL and lipopolisacharides in essential cellular agents of plaque destabilization, macrophages. On the other hand, EL promotes monocytes/macrophages adhesion and cleaves HDL-phosphatidylcholine (HDL-PC) into bioactive molecules, lysophosphatidylcholines (lyso-PC) and free fatty acids (FFA) capable to activate inflammatory cytokines, via its phospholipase A1 activity. The main objective of this study was to evaluate the relationship between the following: the expression of EL in human carotid atherosclerotic plaque and serum level of EL versus clinical presentation and degree of plaque instability. Final study population included 66 patients with proven significant (>70%) unilateral stenosis of carotid artery admitted for carotid endarterectomy (CEA). Patients were grouped as follows: 1) asymptomatic group (42 pts) and 2) symptomatic group (24 pts). The carotid stenosis was considered symptomatic if a patient had suffered a focal neurological symptom (ipsilateral stroke, transient ischemic attack or monocular blindness), sudden in onset and referable to the respective carotid artery within 4 months of CEA. Histological examination was performed in order to find features indicative of plaque vulnerability. Plaques were defined as: 1) fibrous (F) covered by a smooth luminal surface, 2) ulcerated non-complicated (UNC) with thin, fissured or ruptured cap, and 3) ulcerated-complicated (UC) with thin fissured or ruptured cap, intra plaque hemorrhage and/or thrombus. Immunohistochemistry was performed using the rabbit clonal anti-human CD163 (specific for macrophages) and rabbit anti-EL antibody. The expression of EL was evaluated on a semi-quantitative scale as follows: 1) (A) low staining (0–25% positive cells), and 2) (B) high staining (>25% positive cells). EL plasma protein levels were analyzed in 55 patients by ELISA method. ----- Results: Symptomatic patients more frequently had highly significant (95-99%) stenosis (p=0,027) and echolucent zones in plaques (p=0,039), but there was no significant difference between the groups in histological features (p=0,213). In F plaques the EL immunostaining was weak (typ A) and detected in endothelial layer and in cells within the fibrous cap. In contrary, in UC plaques the EL immunostaining was more pronounced (type B) and localized between the necrotic core and the fibrous cap where macrophages dominated. The intensity of the EL immunostaining type B was most frequently observed in UC plaques, followed by the UNC and F plaques (79:50:33%, p=0,004). EL plasma levels were significantly higher in patients with arterial hypertension (p=0,004), smokers (p=0,058), patients taking ACE inhibitors (p=0,018) and Ca blockers (p=0,05). EL plasma levels were similar in patients with the EL immunostaining A and B (p= 0,378) and were not significantly correlated with hsCRP, IL-6, HDL and LDL plasma levels. Compared to the no symptoms group the new symptoms group (symptoms present within 4 month referable to carotid artery) and the old symptoms group (other symptomatic patients) had significantly higher EL plasma level (p=0,011) whereas the two symptomatic groups of patients showed no significant difference. The confirmation of hypothesis that the EL is more expressed in carotid plaques of symptomatic patients and in vulnerable plaques proves its connection with plaque destabilization. This connection is also supported by the fact that EL is mostly expressed in region between the necrotic core and the fibrous cap of vulnerable plaques where macrophages dominate. In line with some previous studies, there was no correlation between histological type and symptoms, which suggests the lack of sensitive and specific histological criteria to confirm plaque vulnerability. The significant relationship between the EL immunostaining and histologic features as well as the EL immunostaining and symptoms suggests that EL could be used in future as one of the markers of plaque vulnerability. EL plasma levels were increased in symptomatic patients irrespective to time of occurrence and localization of symptoms. Furtermore, EL plasma levels were not associated with the intensity of EL immunostaing within carotid plaques. This suggests that EL plasma level is not significantly influenced by increased focal expression of the EL in one plaque. Rather it is influenced by global endothelial disfunction and generally increased expression in all arteries. Higher levels of EL plasma levels were found in patients with arterial hypertension and smoking as two risk factors capable of inducing endothel disfunction, the former mechanically and the latter chemically. HsCRP and IL-6 levels where higher than in healthy population, but there was noconnection to symptoms, probably due to the advanced stage of atherosclerosis. This implicates that EL plasma level is at this stage of disease probably a more sensitive marker of cerebrovascular (and possible cardiovascular) events than hsCRP.