Anti-inflammatory statins

Furthermore, there is some evidence for pleiotrophic effects (e.g., effects on hemostasis, vascular function, anti-inflammatory effects, and stabilizing effects on atherosclerotic plaques) of statins. The clinical relevance of this (and the potential difference between the various statins) is at present uncertain but subject to intense investigation. 

Other agents, including selenium, vitamin E, lycopene, green tea, nonsteriodal anti-inflammatory agents, isoflavones, and statins, are under investigsation for prostate cancer and show promise. Selenium is a naturally occurring trace element that is an essential nutrient in the human diet.8 However, none of these agents is currently recommended for routine use outside a clinical trial. 

Weitz-Schmidt G. Statins as anti-inflammatory agents. Trends Pharmacol Sci 2002 23(10) 482—486. 

Blanco-Colio LM et al (2003) Anti-inflammatory and immunomodulatory effects of statins. Kidney Int 63 (1) 12—23... 

The exact mechanism of these drugs is unclear, but they probably work by binding to a specific nuclear receptor known as the peroxisome proliferator activated receptor.52,141 This receptor, found primarily in the liver and adipose tissues, affects the transcription of genes that affect lipid metabolism.89 Fibrates activate this receptor, thereby mediating several changes at the nuclear level that ultimately cause a decrease in triglycerides and other beneficial changes in plasma lipid metabolism.30,52 In a manner similar to the statins, fibrates may also exert anti-inflammatory, antioxidant, and other beneficial effects in addition to their positive effects on plasma lipids.42,49... 

There is evidence that cholesterol contributes to AD by enhancing Ab synthesis. This provides a theoretical basis for the use of statins to lower the blood cholesterol concentration. There is also recent evidence that the statins have unexpected anti-inflammatory properties by reducing the adhesion and activation of leucocytes which may contribute to the moderate improvement in the cognition scores which have been observed in a placebo-controlled trial. 

Clinical efficacy of anti-inflammatory properties has been shown in several trials independent of their lipid-lowering effects (18,19). Statins reduce CRP levels and it is known that elevated CRP levels are associated with restenosis. Counter intuitively, however, several trials tested statins for restenosis prevention and were disappointing (20-23). The only trial that showed reduction in restenosis was the REGRESS trial (24), which used pravastatin 40 mg once daily for a period of two years. In this study, the binary restenosis assessed at two... 

A number of drugs should be avoided in HF including antiar-rhythmic agents, calcium channel blockers, antipsychotics, antihistamines, corticosteriods, and nonsteroidal anti-inflammatory drugs. Metformin and thiazolidinediones should be used with caution in HF with diabetes. Trials of statins have generally excluded patients with symptomatic HF but two studies with morbidity and mortality outcomes in HF are now under way. 

Dietary compounds are represented in a number of highly successful drugs such as lovastatin 31 and salicylic acid, the archetypal statin and non-steroid anti-inflammatory drugs, respectively. Lovastatin occurs in the red yeast of rice Monascus ruber),91 an ingredient of Eastern cuisine used to give a red colour to the Pekinese duck, while salicylic acid is ubiquitous in plants.92 Other important dietary drug candidates are curcumin 32 from turmeric and capsaicin from hot pepper 33,93 while traces of pharmaceutical benzodiazepines (including diazepam) occur in common edible plants such as potatoes and cherries.5... 

PUFAs are potent inhibitors of the HMG-CoA reductase enzyme and similar to statins are useful in the treatment of hyperlipidemias (99-102). Statins enhance plasma AA levels and decrease the ratio of EPA to AA significantly (100). This finding suggests that PUFAs mediate many actions of statins (103) and that this could be one mechanism by which they lower cholesterol levels. Statins and PUFAs have many overlap actions such as the inhibition of IL-6 and TNF-a production and NF-kB activation plus the ability to enhance eNO production thus, both possess anti-inflammatory actions and both are useful in atherosclerosis, coronary heart disease, osteoporosis, stroke, Alzheimer s disease, and inflammatory conditions such as lupus and cancer (3, 4, 94, 104-121). These similar and overlap actions strongly indicate that the molecular mechanisms of actions of statins and PUFAs are similar, if not identical. Furthermore, when a combination of statins and PUFAs are given together, a synergistic beneficial effect was seen in patients with combined hyperlipemia (122). 

For subarachnoid hemorrhage surgical clipping of the causative aneurysm or resection of the arteriovenous malformation is the mainstay of treatment. Endovascular coiling of the aneurysm can also be performed. Post-operative infection (either brain or respiratory) is an uncommon complication and not believed to be any more common than after other invasive surgical procedures. Hypervolemic-hemodilution and hypertensive (HHH) therapy is used to prevent spasm. There may be a role for anti-inflammatory measures for the prevention of vasospasm and delayed cerebral ischemia, as shown in a recent pilot study of patients treated with statins (Lynch et al., 2005). 

The mechanism of how lowering cholesterol affects beta amyloid production is still unclear studies have demonstrated that statins do not alter beta amyloid morphology (Hoglund et al., 2004). It may be that the neuroprotective properties of statins are due to antioxidant and anti-inflammatory effects. 

NMDA receptor modulators (47-50)], monoamine oxidase B (MAO B) inhibitors (51-55), antioxidants (52, 56-59), nootropics (41, 60), lipid-lowering agents (e.g., statins) (61), insulin (62), anti-inflammatory agents (63-67), and estrogen supplementation (63, 65, 66, 68, 69). Because several other reviews are available that compare these therapeutic approaches (70-77), the remainder of the present chapter focuses on ion channel modulation approaches to cognition enhancement. 

In the patient with chronic angina, the drugs commonly used seem to offer important myocardial protection Thus, (3-blockers, ACE inhibitors and most probably angiotensin receptor blockers, statins, Ca2+ channel blockers, all are in their way cardioprotective. Nitrates and more importantly nicorandil are worthwhile options. Trimetazidine and drugs producing a shift towards preferential glucose oxidation would also be a consideration. A number of studies stress that they may produce an improvement in ischemic cardiomyopathy, probably through an anti-inflammatory action.261... 

The value of statins has already been described. Recent work shows that they may reduce infarct size through an anti-inflammatory effect.265 Their action in heart failure is... 

An interesting aspect of the use of biomarkers as surrogates is exemplified by the statins, which lower serum low-density lipoprotein cholesterol. It has recently been shown that their contribution to improved prognosis in patients with cardiovascular disease is not entirely due to lowering of cholesterol and may be related to anti-inflammatory activity. Thus, the apparently obvious surrogate turns out to be an inadequate biomarker for predicting outcome. 

Much of the prior discussion has focused upon statin effects on cholesterol pathways. However, recent data suggest statin benefit in AD may occur via mechanisms completely independent of cholesterol lowering. For example, samples are known to modulate isoprenylation pathways and have potentially very potent anti-inflammatory activities [161]. Indeed, inhibition of proteins that are dependent upon isoprenylation, such as the Ras GT-Pase superfamily, has been suggested to be an import step in the inhibition of iNOS stimulated cytokine release [161]. In order to better understand... 

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