Inflammation: A pivotal link between autoimmune diseases and atherosclerosis☆
Section snippets
Epidemiology of cardiovascular disease in prototypic autoimmune diseases (SLE and RA)—extent of the burden
Cardiovascular (CVS) diseases secondary to accelerated atherosclerosis are now accepted as a leading cause of morbidity and mortality in patients suffering from systemic autoimmune diseases [1], [2]. Some of the most remarkable data that has come to surface linking autoimmunity and atherosclerosis stems from epidemiological studies of patients with autoimmune diseases. Patients having prototypic autoimmune disease such as SLE and RA have a significantly higher risk and increased prevalence of
Inflammation: a cardiovascular risk factor-cutting into the heart of cardiovascular affection
Epidemiological observations have linked inflammation with the cardiovascular events [10]. Clinical epidemiological observations strongly suggest that, together with classical conventional risk factors, other mechanisms (non-conventional/disease-specific factors) promote accelerated atherosclerosis in diseases like SLE and RA [7], [11]. The excess risk observed in autoimmune disease appears to be driven by systemic inflammation, directly or indirectly through its damaging effects on the
Autoimmune disease and atherosclerosis: two diseases, one pathobiology
An increasing body of evidence supports that atherosclerosis shares many similarities with other chronic inflammatory autoimmune diseases such as RA [13]. Many parallels have emerged between the paradigm of inflammation in the pathogenesis of atherosclerosis and the mechanisms of inflammation in the pathogenesis of autoimmune diseases such as RA and SLE.
When comparing atherosclerosis to RA, a bone fide autoimmune disease, an interesting pattern of similarities can be deduced (Fig. 1), in that,
Endothelial Dysfunction (ED)—a central determinant in autoimmune disease states and atherosclerosis
Endothelial dysfunction is a key event in atherogenesis appearing long before the formation of a structural atherosclerotic lesion [22]. ED is common in most inflammatory states [23]. Chronically raised levels of inflammatory mediators may drive the inflammation that subsequently contributes to endothelial damage (Fig. 2).
Chronic ED and vascular inflammation induced both by conventional risk factors and systemic inflammation are important mechanisms in atherogenesis [22].
Chronic inflammation
C-Reactive Protein (CRP): a mediator and marker of inflammation and cardiovascular risk
Systemic inflammation may be regarded as accelerating the atherosclerotic process. Systemic levels of inflammatory mediators such as CRP have been associated with CVS risk in the general population. Epidemiological and clinical studies have shown strong and consistent relationships between markers of inflammation and risk of future CVS events, the most reliable, surpassing all inflammatory and lipid markers in predicting CVS events, currently being, high-sensitivity CRP (hsCRP) [30].
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (Statins): immunomodulatory and anti-inflammatory effects
HMG-CoA reductase inhibitors, originally designed to decrease cholesterol levels have demonstrated encouraging results in lowering CVS morbidity and mortality rates in the general population and in high risk populations [36]. Accumulating evidence suggests that statins, other than lowering cholesterol levels, also influence multiple steps in the inflammatory process, including leucocyte migration and adhesion, T cell activation, nitric oxide (NO) bioavailability, generation of free radicals and
Conclusions
The increased prevalence of cardiovascular mortality in RA and other autoimmune diseases cannot be merely explained by the presence of traditional atherosclerotic risk factors. Inflammation plays a pivotal role in atherosclerosis. The premature atherosclerosis may be a consequence of the chronic inflammation that is part and parcel of autoimmune diseases like RA and SLE. Increases in CRP have been shown to predict future CVS events in the general population. Thus, one explanation for the excess
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