Gene Expression of Adhesion Molecules in Endothelial Cells from Patients with Peripheral Arterial Disease Is Reduced after Surgical Revascularization and Pharmacological Treatment
Atherosclerosis is an inflammatory disease characterized by immunological activity, in which endothelial dysfunction represents an early event leading to subsequent inflammatory vascular damage. We investigated gene expression of the adhesion molecules (AMs) ICAM-1, VCAM-1, and 1-integrin in endothelial cells (ECs) isolated from venous blood (circulating EC, cEC) and purified from femoral plaques (pEC) obtained from 9 patients with peripheral artery disease (PAD) submitted to femoral artery thrombendarterectomy (FEA). In addition, in peripheral blood mononuclear cells (PBMCs) of the same subjects, we investigated gene expression of IFN- , IL-4, TGF- , and IL-10. Patients were longitudinally evaluated 1 month before surgery, when statin treatment was established, at the time of surgery, and after 2 and 5 months. All AM mRNA levels, measured by means of real-time PCR, in cEC diminished during the study, up to 41–50% of initial levels at followup. AM mRNA expression was significantly higher in pEC than in cEC. During the study, in PBMCs, TGF- and IL-10 mRNA levels remained unchanged while IFN- and IL-4 levels increased; however, the ratio IFN- /IL-4 showed no significant modification. In PAD patients, FEA and statin treatment induce a profound reduction of AM expression in cEC and affect cytokine mRNA expression in PBMCs. 1. Introduction Atherosclerosis (ATH) is an inflammatory disease characterized by intense immunological activity [1] that involves the formation of lesions in the arteries and is characterized by lipid accumulation, inflammation, cell death, and fibrosis. Recruitment of monocytes and lymphocytes from the peripheral blood to the intima of the vessel wall represents the primary event in atherogenesis. Among the factors involved in ATH, the local presence of high amounts of low-density lipoproteins (LDL) has a key role [2]. Healthy endothelium is an important barrier to the free passage of LDL and immune cells to the underlying interstitium, and dysfunction of endothelial cells (EC) is considered an early step in atherogenesis. EC dysfunction results in increased activation of these cells [3], sustained by upregulation of adhesion molecules (AMs) such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). VCAM-1 expression precedes lesion formation and correlates positively with the extent of exposure to plasma cholesterol [4]. Cells can then change their shape and migrate at the surface of the endothelium to reach the junctions. Recently, we have confirmed the occurrence of extensive alteration of
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