Atherogenesis and autoimmune disease: the model of lupus

Abstract

Accelerated atherosclerosis is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Certain 'classic' risk factors are associated with atherosclerosis risk in SLE. However, these factors alone do not fully explain the excess risk observed. Atherosclerosis is increasingly recognized as a chronic inflammatory condition and in SLE, complement activation and immune complex formation may promote atheroma development. Similarly, autoantibody production, especially those in the anticardiolipin (ACLA) family are gaining increasing attention. The role of steroids may not be completely straightforward, low doses may have a beneficial anti-inflammatory role whereas higher doses may exacerbate metabolic factors. In contrast, antimalarials have a beneficial effect on lipids as well as anti-inflammatory and anti-platelet effects. The aetiology of atherosclerosis in SLE is therefore multifactorial. A better understanding of the interface of autoimmunity and atherogenesis in the context of SLE will benefit lupus patients and will also help us better understand the pathogenesis of atherosclerosis in general.

HDAC Inhibition in Lupus Models

“…People with SLE have many different symptoms; the most common ones include extreme fatigue, painful or swollen joints (arthritis), unexplained fever, skin rashes and kidney dysfunction. The severity of these problems increases with age and disease duration (2)(3)(4)(5). In SLE, the major cause of morbidity and mortality is lupus nephritis (LN), which affects over half of all SLE patients.…”

Atherogenesis and Vascular Disease in SLE

“…Most of the patients with SLE and aPL antibodies who developed thrombosis had other thrombotic risk factors (Erkan et al, 2007). Interestingly, after adjusting for other risk factors, SLE itself remains independently associated with thrombotic events (Bruce, 2005). Thrombosis is frequent in early SLE and is associated with a significant mortality; therefore, the identification of possible modifiable risk factors and the establishment of efficacious strategies of prevention and treatment are vital.…”

“…Stroke (both ischaemic and haemorrhagic) and SLE cerebral vasculopathy are far more frequent. While ischaemic stroke in SLE is strongly associated to antiphospholipid syndrome, atherosclerosis (Bruce, 2005) and Libman-Sacks endocarditis (Moyassaki et al, 2007), factors that contribute to hemorrhagic stroke are less clear. The predominant pathology finding in CNS vessels in SLE patients is a noninflammatory small vessel vasculopathy involving small arterioles and capillaries.…”

“…A patient with SLE and cardiovascular disease has on average one less traditional risk factor than people in the general population with a similar cardiovascular condition (Bruce, 2005;Urowitz et al, 2007) and the baseline 10-year coronary heart disease and stroke risk (after adjusting for Framingham score) for all patients with SLE is 7.5-17-fold higher (Esdaile et al, 2001). This is one of the reasons why the relative importance of the individual traditional risk factors differs between patients with SLE and the general population.…”

Accelerated Atherosclerosis in Patients with Systemic Lupus Erythematosus and the Role of Selected Adipocytokines in This Process

“…Identiication of mechanisms common to inlammation and CVD might be of considerable interest especially in the context SLE, which is, potentially, a model disease for gaining a deeper insight into such mechanisms [13]. Generally, the relationship of adipokines to inlammation and coronary atherosclerosis in patients with SLE has not been fully elucidated [57]; for example, it has not been determined whether adiponectin concentrations in SLE result from metabolic disorders or inlammatory processes and nor has it been determined whether adipokine abnormalities associated with connective tissue diseases contribute to disease development or are caused by inlammation induced by other pro-inlammatory factors [58].…”