Impaired endothelial function in systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) patients suffer from excess cardiac deaths due to accelerated atherosclerosis. Endothelial dysfunction is a marker of early atherosclerosis. We tested the hypothesis that SLE patients have impaired endothelial function and assessed the relationship between endothelial function and clinical outcome over the subsequent five years. Thirty-six female SLE patients were compared with 22 healthy age and sex matched controls. Endothelial dependent vasodilatation (EDD) was assessed at the brachial artery in response to shear stress. Endothelium-independent dilatation induced by glyceryl trinitrate was also measured. Patients were followed for up to five years and the development of damage in the cardiovascular and other systems recorded. SLE patients showed significantly impaired endothelial function (median EDD 5.6%, IQR 3.1-7.2%) compared with healthy controls (median EDD 8.0%, IQR 6.3-9.3%; P = 0.001). Endothelium independent dilatation did not differ between the two groups. Endothelial function was significantly worse in postmenopausal compared with premenopausal women (median EDD 6.6%, IQR 3.9-7.8% versus 3.1%, IQR 2.6-5.1%; P = 0.016). Total cholesterol was inversely correlated with endothelial function in SLE patients (Spearman correlation r = -0.422, P = 0.025). There was no relationship between endothelial function and the development of damage in any organ system, including the cardiovascular system during patient follow-up. Patients with SLE have impaired endothelial Lupus (2007) 16, 84-88.

Atorvastatin therapy improves endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8 weeks controlled trial

“…The effect of atorvastatin on FMD in our study was independent on baseline serum lipids levels, corroborating previous studies in patients with hypertension [31], diabetes mellitus [32] and dyslipidaemia [33], and supporting the notion that the endothelial benefits of atorvastatin are independent of the reduction in serum lipids levels. In the present study we also confirmed previous findings of reduced FMD in SLE patients as compared to healthy controls, suggesting significant endothelial dysfunction in SLE patients [14,34,35].…”

Nitric oxide – the endothelium-derived relaxing factor and its role in endothelial functions

“…(Katušic and Vanhoutte 1986;Rubanyi and Vanhoutte 1986 a,b;Rubanyi 1988;Yanagishawa et al 1988;Lüscher et al 1992). It participates and plays a substantial role in the generation of various diseases like atherosclerosis (Ross 1993(Ross , 1999Heitzer et al 1996;Besler et al 2008;Heistad 2008), essential hypertension (Lüscher 1988;Vanhoutte 1992;Taddei et al 1995;Besler et al 2008), diabetes mellitus and diabetic vasculopathies (Makimattila et al 1996;Bakker et al 2009;Nathanson and Nyström 2009), chronic obstructive pulmonary disease -COPD (Peinado et al 2008), rheumatoid arthritis (Hansel et al 2003;Szekanecz and Koch 2008), psoriatic arthritis (Gonzalez-Juanatey et al 2007), osteoarthritis (Miller et al 2007), ankylosing spondylitis (Sari et al 2006), systemic lupus erythematosus (Piper et al 2007), cancer metastasis (Johansson et al 2010;Takala et al 2010), migraine and stroke (Besler et al 2008;Elliott 2008), anaphylactic and traumatic shock (Menardi et al 2006;Shi et al 2007;Nakashidze 2009), systemic inflammatory response syndrome (Neary and Redmond 1999;Hingorani et al 2000;Menardi et al 2006), NO-induced vasoplegia in sepsis (Stawicki et al 2008;Funk et al 2009) and cardiac surgery …”

“…Due to microangiopathy, ophthalmologic, neurologic and nephrologic complications may occur. Microangiopathies are characterized by roughed-up basal membrane, proliferation, focal desquamation and alteration in endothelium cell shape, stack of granulocytes and adherence of platelets to the endothelium (Pieper and Gross 1991). The wall of small blood vessels becomes so thick and weak that they bleed, leak protein, and reduce blood flow.…”

“…The mechanisms of the effects of high glucose concentrations on endothelium-dependent vascular reactivity are not clear yet. It has been suggested that decreased production of PGI 2 and PGE 1 , increased formation of vasocontractile prostaglandins and ROS, protein glycosylation, reduced output and impact of NO, activation of the renin-angiotensin system, as well as changes in α-adrenergic receptors might be involved in these mechanisms (Baynes 1991;Pieper and Gross 1991;Getz 1993;Tesfamariam 1994;Muscogiuri et al 2008). …”

Endothelial Dysfunction in Systemic Lupus Erythematosus: Evaluation with 13N-Ammonia PET

“…Endothelial dysfunction has been demonstrated in SLE using brachial artery Doppler ultrasound (7). However, such measurements are unable to detect subclinical atherosclerosis.…”