Effect of anti TNFalpha therapy on arterial diameter and wall shear stress and HDL cholesterol
Introduction
It has been recently described that anti-tumor necrosis factor alpha (TNFalpha) therapy improves endothelial function, measured as both flow-mediated vasodilatation (FMD) of the brachial artery and increased forearm blood flow after acetylcholine infusion, in subjects with rheumatoid arthritis (RA) and advanced heart failure. The improvement has been ascribed to increased nitric oxide (NO) synthesis/release [1], [2]. However, it has been demonstrated that TNFalpha has endothelium-dependent and endothelium-independent vasodilator properties. The mechanism underlying this effect probably involves activation of endothelial NO synthase and consequent relaxation of smooth muscle cells [3], [4], [5], [6]. On the basis of this knowledge, we investigated wall shear stress of common carotid and brachial arteries and endothelial function of brachial artery in subjects with RA, a chronic inflammatory disease associated with elevated levels of TNFalpha at baseline and after infliximab. Moreover, TNFalpha seems to interact with plasma lipoproteins. High density lipoproteins (HDL) have been reported to protect isolated rat hearts from ischaemia-reperfusion injury by reducing cardiac TNFalpha [7]. On the other hand, intravenous infliximab therapy, at least in one report, was found to reduce HDL-cholesterol levels [8]. Therefore, in the present study, we have also evaluated plasma lipoprotein modifications after infliximab therapy.
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Patients
Ten patients (four males and six females) with RA, according to the American Rheumatism Association criteria and eligible for anti-TNFalpha treatment, were enrolled from outpatient clinic [9]. All patients gave an informed consent to the study protocol and were admitted to hospital for drug infusion and endothelial function evaluation. The investigation conformed to the principles outlined in the Declaration of Helsinki. Ongoing therapy was not modified during hospitalization. Patients were
Results
Clinical and biochemical characteristics and vascular parameters of RA and control subjects are reported in Table 1. Age, blood lipids, glucose, BMI and blood pressure were comparable in the two groups. IDT of common carotid artery was higher (5.9 ± 0.2 mm versus 5.4 ± 0.2 mm; P = 0.05) and τP lower (21.1 ± 1.1 dynes/cm2 versus 26.1 ± 1.6 dynes/cm2; P = 0.03) in RA subjects compared to controls. Brachial artery parameters showed similar differences though statistical significance was not reached.
Discussion
Over the last few years, evidence is growing that inflammatory response might play a role in the pathogenesis of atherosclerosis [15]. The metabolic pathways are not well understood though several mediators have been identified. TNFalpha and other cytokines stimulate the release of adhesion molecules, inhibit endothelial antithrombotic activity, influence endothelial function, thus contributing to the development of atherogenesis [16], [17]. More recently, two studies have reported the
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