Elsevier

Atherosclerosis

Volume 177, Issue 1, November 2004, Pages 113-118
Atherosclerosis

Effect of anti TNFalpha therapy on arterial diameter and wall shear stress and HDL cholesterol

https://doi.org/10.1016/j.atherosclerosis.2004.04.031Get rights and content

Abstract

It has been recently hypothesized that both TNFalpha and anti TNFalpha treatment have a stimulating effect on nitric oxide synthesis and release. Moreover, an in vitro experiment has demonstrated that HDL-cholesterol binds TNFalpha. Aims of our study were to investigate wall shear stress of peripheral arteries and endothelial function of brachial artery in subjects with Rheumatoid Arthritis (RA) at baseline and after infliximab. Moreover, we evaluated the effect of anti TNFalpha therapy on lipid profile. Ten patients with RA received infliximab therapy at weeks 0, 2 and 6. Lipids and vascular parameters were measured before and the day after each infusion. After the first treatment, FMD increased (3.7 ± 1.9% versus 17.5 ± 2.9%, P < 0.01) and common carotid and brachial artery diameters decreased (5.9 ± 0.2 mm versus 5.5 ± 0.2 mm; 3.5 ± 0.4 mm versus 3.1 ± 0.4 mm, respectively, P < 0.005). Common carotid and brachial artery wall shear stress increased (21.1 ± 1.1 dynes/cm2 versus 23.9 ± 1.4 dynes/cm2; 42.0 ± 4.7 dynes/cm2 versus 51.6 ± 5.7 dynes/cm2, P < 0.01). Similar results were observed after the second and third infusion. All these parameters returned to pre-treatment level at the following infusion. HDL-cholesterol and apolipoprotein AI significantly decreased after each treatment (1st treatment: 1.4 ± 0.05 mmol/L versus 1.2 ± 0.06 mmol/L, P < 0.01; 1.73 ± 0.05 g/L versus 1.57 ± 0.02 g/L, P < 0.03).

The present data show vasoconstriction and an increase of wall shear stress in studied arteries after infliximab. HDL cholesterol is reduced by treatment and does not seem to influence FMD.

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.

Section snippets

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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