Review Endothelial dysfunction and vascular stiffness in systemic lupus erythematosus: Are they early markers of subclinical atherosclerosis? Enrico M. Zardi ⁎, Antonella Afeltra Department of Clinical Medicine, Immunology and Rheumatology, University Campus Bio-Medico of Rome, Italy abstract article info Article history: Received 12 May 2010 Accepted 19 May 2010 Available online 26 May 2010 Keywords: Systemic lupus erythematosus (SLE) Atherosclerosis (ATS) Inflammation Intima-media thickness (IMT) Endothelial dysfunction Vascular stiffness Color Doppler sonography In systemic lupus erythematosus (SLE), the risk of development of cardiovascular disease is dramatically increased. Inflammatory and immune-mediated mechanisms, favouring early alterations of the arterial wall are strongly involved in promoting the development of atherosclerosis (ATS) in young SLE patients. In SLE, sonographic measurements of carotid intima-media thickness are able to recognize clinical, but not always subclinical, ATS. On the contrary, assessment of endothelial function and vascular stiffness through sonography-based techniques may be useful to reveal or exclude subclinical ATS. More efforts should be done to find a comprehensive approach to the study of subclinical ATS in SLE patients, since an early diagnosis may have a significant value in preventing the development of major vascular diseases. © 2010 Elsevier B.V. All rights reserved. Contents 1. Pathophysiology of ATS in SLE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 684 2. Vascular stiffness and endothelial dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 685 3. Diagnostic methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 685 4. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 685 Take-home messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 686 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 686 Atherosclerosis (ATS) in SLE is a multifactorial process involving inflammatory, immune-mediated mechanisms, oxidative stress and endothelial dysfunction. Early alterations of the arterial wall in young SLE patients document the development of accelerated ATS at an early age. Here, we emphasize the importance of recognizing early vascular wall alterations to prevent the development of other cardiovascular complications. 1. Pathophysiology of ATS in SLE Immune system activation, chronic inflammation and oxidative stress favour the development of ATS in SLE [1]. Before atherosclerotic lesions arise, vascular wall permeability, elasticity and thickness are deranged due to increased endothelial dysfunction and inflammation [2]. Autoantibody production is increased in SLE [3,4] but its role in inducing accelerated ATS is debated; however, it may favour the increase of oxidative stress [5,6], endothelial cell damage [7] and apoptosis leading to accelerated atherosclerosis [8]. Immune com- plexes in the arterial wall reduce the ability of the endothelium and macrophages to catalyze the hydroxylation of cholesterol, thus favouring its build-up in the endothelial wall [9]. Circulating oxLDL/beta2GPI complexes may be uptaken by macrophage Fc-gamma receptors leading to foam cell formation [10,11] that, recruited and captured by endothelial adhesion mole- cules, favours atherogenic peroxidation; furthermore, pro-inflamma- tory cytokines directly damage the endothelium. Dysregulated immune system activation exacerbates the pro-inflammatory state (for example, HDL changes its function and turns into pro-inflamma- tory HDL), while the damaged endothelium becomes unable to counteract this situation. In some cases a severe dysregulated immune system activation combined with different stress stimuli may lead to the catastrophic multi-organic failure [12]. Autoimmunity Reviews 9 (2010) 684–686 ⁎ Corresponding author. Università “Campus Bio-Medico” Via Àlvaro del Portillo, 200 – 00128 Roma, Italy. E-mail address: e.zardi@unicampus.it (E.M. Zardi). 685 1568-9972/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.autrev.2010.05.018 Contents lists available at ScienceDirect Autoimmunity Reviews journal homepage: www.elsevier.com/locate/autrev