Put your heart into the joint benefits of statins!

نویسنده

  • Frances C Hall
چکیده

The recognition that systemic inflammatory diseases are associated with accelerated atherosclerosis offers the prospect of reducing morbidity and mortality of affected patients by attention to traditional cardiovascular risk factors. For example, in most studies of mortality in patients with rheumatoid arthritis, excess cardiovascular deaths predominate, with a risk ratio of about 2 (reviewed by Van Doornum [1]). Several recent observations indicate that not only is chronic inflammation associated with ather-osclerosis but aberrant cellular and humoral immune responses are integral to its pathogenesis (reviewed by Sherer and Shoenfeld [2]). It has become apparent that therapeutic interventions in chronic inflammatory and car-diovascular disease might be closely intertwined. Also emerging is the realisation that agents prescribed as either immunomodulators or lipid modulators might be acting in both capacities. Statins are particularly topical in this regard. Statins (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase inhibitors) are widely prescribed for individuals at increased risk from cardiovascular disease (reviewed by Singh and Mehta [3]). HMG-CoA reductase is an enzyme of the cholesterol biosynthetic pathway that catalyses the conversion of HMG-CoA to mevalonic acid. Downstream metabolites in this pathway include farnesyl pyrophosphate and geranylgeranyl pyrophosphate, which are required for post-translational prenylation of a range of moieties, including signalling intermediaries, tRNA and coenzyme Q in the electron transport chain (reviewed in Holstein et al. [4]). It follows that, in addition to decreasing cholesterol levels, statins can be expected to have diverse effects on cell physiology. In 1995 it was reported that pravastatin decreased the incidence of haemodynamically significant rejection episodes in cardiac transplant patients and that this effect was independent of the decrease in cholesterol levels [5]. Subsequent studies have revealed a wide range of statin-sensitive immunological pathways. For example, statins bind to β 2 integrin and thereby block T-cell costimulation by means of lymphocyte-function-associated antigen-1 (LFA-1) [6]. Statins inhibit interferon-γ-inducible class II transactivator (CIITA) to decrease the induction/upregula-tion of MHC class II molecules on professional and non-professional antigen-presenting cells [7]. In monocytes and/or macrophages, statins decrease chemotaxis, lipopolysaccharide (LPS)-mediated release of tumour necrosis factor-α (TNF-α) activation of NO synthase [8] and LPS-stimulated secretion of matrix metalloproteinase-9 [9]. These immunological effects indicate that statins might interfere with the initiation and amplification of immune/inflammatory responses. The appeal of statin therapy in chronic inflammatory disease is further enhanced by accumulating evidence that statins might influence bone metabolism (reviewed by Bauer [10]). Although the observation that statins prevented rejection episodes after cardiac transplant suggests …

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عنوان ژورنال:
  • Arthritis Research & Therapy

دوره 5  شماره 

صفحات  -

تاریخ انتشار 2003