Anti-inflammatory Properties Of Statins Research Articles

Antioxidant Effects of Statins by Modulating Nrf2 and Nrf2/HO-1 Signaling in Different Diseases.

Statins are competitive inhibitors of hydroxymethylglutaryl-CoA (HMG-CoA) reductase and have been used to treat elevated low-density lipoprotein cholesterol (LDL-C) for almost four decades. Antioxidant and anti-inflammatory properties which are independent of the lipid-lowering effects of statins, i.e., their pleiotropic effects, might be beneficial in the prevention or treatment of many diseases. This review discusses the antioxidant effects of statins achieved by modulating the nuclear factor erythroid 2 related factor 2/ heme oxygenase-1 (Nrf2/HO-1) pathway in different organs and diseases. Nrf2 and other proteins involved in the Nrf2/HO-1 signaling pathway have a crucial role in cellular responses to oxidative stress, which is a risk factor for ASCVD. Statins can significantly increase the DNA-binding activity of Nrf2 and induce the expression of its target genes, such as HO-1 and glutathione peroxidase) GPx, (thus protecting the cells against oxidative stress. Antioxidant and anti-inflammatory properties of statins, which are independent of their lipid-lowering effects, could be partly explained by the modulation of the Nrf2/HO-1 pathway.

Effect of statins on the plasma/serum levels of inflammatory markers in patients with cardiovascular disease; a systematic review and meta-analysis of randomized clinical trials.

The anti-inflammatory properties of statins have been suggested by several researches. However, clinical trials have reported incongruous findings regarding the effect of statins on the levels of inflammatory markers other than high-sensitive C-reactive protein. Therefore, a systematic review and meta-analysis of randomized clinical trials were conducted to illuminate the effect of statins on serum levels of TNF-α, MCP-1, VCAM1, and IL-6 in patients with cardiovascular diseases (CVDs). To find eligible studies, a systematic literature search of the main databases were conducted up to July 2021. The calculation of the effect sizes was conducted by standardized mean difference (SMD) and 95% confidence intervals (CI). The pooled analyses revealed that statins significantly reduced the TNF-α concentration (SMD = -0.99pg/mL; 95% CI -1.43 to -0.55pg/mL; P < 0.001). Regarding dosage, high intensity (SMD = -0.65pg/mL; 95% CI -1.19 to -0.10, P = 0.02) and moderate/low (SMD = -1.16pg/mL; 95% CI -1.84 to -0.47, P = 0.001) intensity statins significantly decreased TNF-α levels. Moderate/low intensity statins administration in < 10weeks treatment duration decreased serum level of TNF-α (SMD = -0.91pg/mL; 95% CI -1.38 to -0.44, P < 0.001). Lipophilic statins with high intensity dosage significantly decreased level of TNF-α (SMD = - 0.73pg/mL; 95% CI - 1.43 to - 0.03, P = 0.04). Statins did not change serum levels of MCP-1, VCAM1, and IL-6 in CVD patients. The analyses indicated that statins have beneficial effects in decreasing serum levels of TNF-α in patients with CVDs.

Abstract TP146: The Effect Of Statins On Thrombus Composition Retrieved By Mechanical Thrombectomy In Acute Ischemic Stroke

Introduction: Ample evidence exists in support of the anti-inflammatory properties of statins which in turn could affect arterial thrombosis. Compositional analysis of thrombi retrieved by MT may provide us with knowledge useful for evaluating the effect of current Statin therapy on thrombus composition. Methods: Consecutive AIS-LVO patients were included. Histopathological evaluation of thrombi retrieved during MT was performed using Martius Scarlet Blue staining (MSB) and immunohistochemistry for von Willebrand Factor (vWF) and anti-citrulinated H3 (CitH3; NETs marker) and the composition of thrombi was determined using image analysis software. Thrombus was considered rich in a given composition if that composition was higher than its overall mean. We reviewed patient’s medication records and cataloged any statin therapy prior to MT. Results: 117 patients were included in this study. The mean density of red blood cells (RBCs), white blood cells (WBCs), platelets (PLT), fibrin (FIB), vWF and NETs (CitH3) in thrombi was 43.4%, 3.7%, 23.6%, 29.3%, 14.3% and 21.1% respectively. Twenty-seven patients were taking Statins at the time of MT. Statins were not associated with pre-thrombectomy IV-tPA, and stroke etiology (p values: &gt;0.05). There was no association between Statins and thrombi composition and type (p values: &gt;0.05 for all thrombus components and type). Additionally, Statins were not associated with MT outcomes including number of device passes and final mTICI score. Conclusion: Pre-stroke Statin therapy was not associated with differences in thrombus composition.

Abstract 281: A Network Meta-analysis Exploring High-intensity Atorvastatin In Contrast Induced Nephropathy

Introduction: The utility of pre-procedure statins prior to coronary angiography has been utilized as an adjunct in the prevention of contrast-induced nephropathy (CIN). This has been attributed to the pleotropic and anti-inflammatory effects of the statin. Whether there is a dose and intensity dependent effect on the prevention of CIN is unknown. Methods: We performed a hierarchical network meta-analysis on all published randomized-controlled trials up to March 2020 to determine whether high-intensity atorvastatin (40mg or 80mg) was superior to lower intensity atorvastatin (20mg or less) and high-intensity or low-intensity statins. We searched PubMed, MEDLINE, Embase, Web of Science and Cochrane database for randomized-controlled studies without restriction to language. Studies published in Chinese was translated using Google Translate. Network meta-analysis was performed using NetMetaXL version 1.6.1. Results: We analyzed 49 trials, comprised of 13,395 patients, comparing five arms of treatment: Moderate/High intensity atorvastatin, Low intensity atorvastatin, Moderate/High intensity other statin, Low intensity other statin and None. There were 1,029 events for CIN (7.68%). In pairways comparisons, Moderate/High intensity atorvastatin reduced CIN by 0.70 (95% CI: 0.54-0.91) when compared to placebo. When compared to Moderate/High intensity other statins, the difference was not statistically significant (95% CI: 0.50-1.08). Conclusion: Moderate to High Dose Atorvastatin was not superior to other statins in prevention of CIN. Further investigation into the anti-inflammatory properties of statins may be helpful in understanding the role of statins as adjunct treatment to standard of care in preventing CIN.

Antinociception induced by rosuvastatin in murine neuropathic pain.

Neuropathic pain, and subsequent hypernociception, can be induced in mice by paclitaxel (PTX) administration and partial sciatic nerve ligation (PSNL). Its pharmacotherapy has been a clinical challenge, due to a lack of effective treatment. In two models of mouse neuropathic pain (PTX and PSNL) the antinociception induced by rosuvastatin and the participation of proinflammatory biomarkers, interleukin (IL)- 1β, TBARS and glutathione were evaluated. A dose-response curve for rosuvastatin ip was obtained on cold plate, hot plate and Von Frey assays. Changes on spinal cord levels of IL-1β, glutathione and lipid peroxidation were measured at 7 and 14days in PTX and PSNL murine models. PTX or PSNL were able to induce in mice peripheral neuropathy with hypernociception, either to 7 and 14days. Rosuvastatin induced a dose dependent antinociception in hot plate, cold plate and Von Frey assays. The increased levels of IL-1β or TBARS induced by pretreatment with PTX or PSNL were reduced by rosuvastatin. The reduction of spinal cord glutathione, by PTX or PSNL, expressed as the ratio GSH/GSSG, were increased significantly in animals pretreated with rosuvastatin. The anti-inflammatory properties of statins could underlie their beneficial effects on neuropathic pain by reduction of proinflammatory biomarkers and activation of glia. The findings of this study suggest a potential usefulness of rosuvastatin in the treatment of neuropathic pain.

High dose statin prophylaxis in cardiopulmonary bypass related surgery: clinical utility

BackgroundPrevious studies from our group demonstrated the anti-inflammatory properties of statins on cardiopulmonary bypass (CPB), through inhibition of neutrophil transendothelial migration. We sought to determine the utility of preoperative statin on patients undergoing cardiac surgery, to investigate any moderating effects on the systemic inflammatory response (SIRS) with CPB, and to evaluate any clinical impact on our patients.MethodsThis is a prospective, randomised controlled trial with national regulatory body approval. Eligible patients were already on oral statin therapy. They were then randomly assigned to either investigation arm (n = 15, atorvastatin 80 mg for 2 weeks before surgery) or control arm (n = 15, no change to current statin therapy). Blood and urine samples were collected at 3 timepoints. Postoperative clinical measures were documented.ResultsPatients in the investigation arm have significantly lower troponin level (p = 0.016), and lower level of urine neutrophil gelatinase-associated lipocalin (NGAL; p = 0.002); thus demonstrating a lesser degree of cardiac and renal injury in these patients. Higher level of Interleukin-8 (IL-8) at baseline (p = 0.036) and 4 h post cross-clamp removal (p = 0.035) in the investiation arm. A similar trend is also observed in Matrix Metalloproteinase-9 (MMP-9; p > 0.05). There were however no differences in clinical outcomes.ConclusionsMaximizing the dose of statin in patients waiting for cardiac surgery has measurable biological effects. There is evidence of less cardiac and renal damage. The use of preoperative statins and in particular, high dose preoperative statin therapy, may prove a useful new tool for optimal preparation of patients for cardiac surgery.Trial registrationEudraCT no. 2012-003396-20. Registered 05 November 2012

English

Antiinflammatory properties of statins and omega-3 fatty acids are well known and documented before. Present work aimed mainly to demonstrate their effects on inflammatory pattern of osteoarthritis (OA) induced in rats. Osteoarthritis was induced by single intraarticular injection of monosodium iodoacetate (MIA) in the right knee joints in a dose level of 24.6 mg/kg body weight. Omega 3 fatty acids and atorvastatin were applied topically(cream form) in a dose levels 1 g/kg and 10 mg/kg body weight respectively either individually or in combination versus diclofenac sodium in a dose level 5 mg/kg body weight for comparison. The treatment started after 24 h of OA induction, daily for 3 weeks. Collective results indicated that the drugs under study significantly decreased serum interleukine-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and total cholesterol (TC). Joint tissue contents showed significant decrease in myeloperoxidase (MPO), matrix metalloproteinase2 (MMP2) along with an increase in tissue inhibitor metalloproteinase2 (TIMP2). Combined form of atorvastatin and omega 3 fatty acids demonstrated marked effects than their individual use as compared to Diclofenac. Key words: Osteoarthritis, monosodium iodoacetate, atorvastatin, omega-3 fatty acids, diclofenac.

Adjunctive therapies for Kawasaki disease

Kawasaki disease (KD) is the most common cause of acquired heart disease in children in developed countries.(1,2) The primary goal of treatment is to prevent coronary artery aneurysms (CAA). Between 10 and 20% of KD patients are resistant to treatment with intravenous immunoglobulin (IVIG) and have an almost nine-fold increased risk of developing CAA.(3) In addition, approximately 80-90% of patients who go on to develop CAA have abnormal coronary artery dimensions on their first echocardiogram and can therefore be identified as high-risk patients. These two subsets of KD patients are candidates for adjunctive therapy, in addition to IVIG. Understanding the mechanism of action of IVIG may provide insight into IVIG resistance and guidance for choosing adjunctive therapies in KD. Therapeutic options in the treatment of refractory KD and patients with early CAA include additional IVIG, glucocorticoids, tumor necrosis factor inhibitors, calcineurin inhibitors and interleukin-1 (IL-1) blockers.(3-10) Animal studies suggest that the anti-inflammatory properties of statins may also be beneficial in blocking CAA progression.(6) It is unlikely that these therapies will be studied in large, randomized controlled trials in the future due to required sample size and funding constraints. Thus, data from the research laboratory may be helpful in guiding selection of the most promising adjunctive therapies.

Role of Integrin β4 in Lung Endothelial Cell Inflammatory Responses to Mechanical Stress.

Simvastatin, an HMG-CoA reductase inhibitor, has lung vascular-protective effects that are associated with decreased agonist-induced integrin β4 (ITGB4) tyrosine phosphorylation. Accordingly, we hypothesized that endothelial cell (EC) protection by simvastatin is dependent on these effects and sought to further characterize the functional role of ITGB4 as a mediator of EC protection in the setting of excessive mechanical stretch at levels relevant to ventilator-induced lung injury (VILI). Initially, early ITGB4 tyrosine phosphorylation was confirmed in human pulmonary artery EC subjected to excessive cyclic stretch (18% CS). EC overexpression of mutant ITGB4 with specific tyrosines mutated to phenylalanine (Y1440, Y1526 Y1640, or Y1422) resulted in significantly attenuated CS-induced cytokine expression (IL6, IL-8, MCP-1, and RANTES). In addition, EC overexpression of ITGB4 constructs with specific structural deletions also resulted in significantly attenuated CS-induced inflammatory cytokine expression compared to overexpression of wildtype ITGB4. Finally, mice expressing a mutant ITGB4 lacking a cytoplasmic signaling domain were found to have attenuated lung injury after VILI-challenge (VT = 40 ml/kg, 4 h). Our results provide mechanistic insights into the anti-inflammatory properties of statins and may ultimately lead to novel strategies targeted at ITGB4 signaling to treat VILI.

Statin use and mortality in rheumatoid arthritis: a general population-based cohort study

BackgroundDual lipid-lowering and anti-inflammatory properties of statins may lead to survival benefits in patients with rheumatoid arthritis (RA). However, data on this topic are limited, and the role of statins...

The anti-inflammatory properties of simvastatin can benefit statin-naïve rheumatoid arthritis patients with associated risks for cardiovascular disease

AbstractBackground: The anti-inflammatory properties of statins are well documented. The aim of this study was to determine if statins may offer therapeutic benefits in rheumatoid arthritis (RA) patients that are also at risk for cardiovascular disease.Methods: Patients with moderately active RA, despite being on maximum disease-modifying anti-rheumatic drugs (DMARDs) therapy, and that were at risk for cardiovascular disease, were screened for inclusion. Eligible patients were randomised into two groups. In this open-label, cross-over design patients in group 1 received simvastatin treatment (20 mg/day) for a period of 3 months in addition to their usual DMARDs, after which they stopped simvastatin treatment and were followed up for a further 3 months while on their usual DMARDs only. Those in group 2 were allowed to continue on their usual DMARDs without simvastatin treatment for the first 3 months of the study, after which they received 20 mg/day simvastatin for a period of 3 months in addition to their...

Statin Use and Osteoarthritis

The Authors’ Reply—We thank Dr Rashid for highlighting the importance our findings,1 as well as the wider generic implications that relate to common treatment pathways and shared mechanisms in the pathogenesis of chronic diseases such as cardiovascular disease and osteoarthritis. There has been much interest in the pleiotropic effects of statins, and a number of studies have provided supportive as well as contrarian evidence. For example, in a large database study, Smeeth et al. showed that for a range of outcomes, statins use was not associated with benefit.2 However, this study did not include osteoarthritis as an outcome, and the statin measure was defined simply as use or non-use, without consideration of potential dose threshold effects. The implication of these results is not that potential pleiotropic effects do or do not occur for a specific drug class such as statins, but whether they are placed within well-constructed and impartial hypotheses using the current evidence base on mechanisms. The broader and generic implications of this study on shared mechanisms are scientifically exciting, and again require a measured and clear approach. Broadly, the mechanisms for osteoarthritis in our paper focused into either anti-inflammatory properties of statins or a modification of the metabolic process. We agree that there is evidence for an inflammatory component to osteoarthritic joints, whilst the evidence on whether this can be mediated systemically in generalised osteoarthritis remains to be established clearly.3 Combined with findings from a Swedish cohort,4 our article suggests that there is a clear need for further research into the shared mechanisms in cardiovascular disease and osteoarthritis, as well as trials on the feasibility of using statins in osteoarthritis. We should also add that osteoarthritis is a ‘complex’ chronic disease that encompasses broader determinants, such as psychological status5 and mechanical factors, which means that both drug and non-drug therapeutic approaches and mechanisms may need to be delineated clearly.

Statins, inflammation and deep vein thrombosis: a systematic review

Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism. The 2009 JUPITER trial showed a significant decrease in DVT in non-hyperlipidemic patients, with elevated C-reactive protein (CRP) levels, treated with rosuvastatin. The effects of statins on thrombosis are unclear, prompting this literature review. A literature search was performed (1950 to February 2011) with MEDLINE, EMBASE, and PUBMED databases including the following keywords: "statins", "hydroxymethylglutaryl-CoA reductase inhibitors", "VTE", "PE", "DVT", and either "anti-coagulation" or "inflammation". Editorials, reviews, case reports, meta-analysis and duplicates were excluded. Inflammatory biomarkers of DVT, include interleukin (IL)-6, CRP, IL-8, and monocyte chemotactic protein 1 (MCP-1). Statin therapy reduces IL-6 expression of CRP and MCP-1, usually elevated in VTE. Reduction of IL-6 induced MCP-1 has been linked to vein wall fibrosis, promoting post thrombotic syndrome (PTS) and recurrent DVT in patients. Also, our review suggests that the anti-thrombotic effects are likely exhibited through the anti-inflammatory properties of statins. This work supports that statin therapy has the ability to decrease the incidence and recurrence of VTE and the potential to decrease PTS. This is mainly due to the anti-inflammatory effects of statins and may explain why normolipidemic patients, with elevated CRP, appear to have the greatest reduction in VTE. Given their low risk of bleeding, statins have the potential to serve as a safe adjunctive pharmacological therapy to current treatments in select patients with VTE, however further investigations into this concept are needed and essential.

Statin Therapy Decreases Risk of Hepatic Steatosis and Lobular Inflammation in Patients with Nonalcoholic Fatty Liver Disease

Purpose: Lipid-lowering therapies, and statins in particular, are routinely used for patients with risk factors for nonalcoholic fatty liver disease (NAFLD). There is unequivocal data that use of statins decreases cardiovascular morbidity and mortality (the leading cause of death in patients with NAFLD). Although use of statins may be safe in patients with NAFLD, the beneficial effect on histologic features of NAFLD remains unknown. The purpose of this study is to assess the histologic benefit of statin therapy in patients with biopsy-proven NAFLD. Methods: 362 patients with biopsy-proven NAFLD registered in the NAFLD Clinical Database at Duke University were analyzed. All demographical, laboratory, and concomitant medication at time of liver biopsy were reviewed. Liver histology was graded and staged for histologic features of NAFLD according to the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. Chi-square test and multiple ordinal logistic regressions were used. Results: Of the 362 patients, 60% were women, with mean age 48±11 years, and mean body mass index (BMI) 37±9. Prevalence of diabetes mellitus, hypertension, and hyperlipidemia was 29%, 59%, and 31% respectively. Statin vs. non-statin lipid lowering agent (i.e. fibrates, niacin, and/or bile-acid binding resin) use was 26% vs. 8%. In univariate analysis, statin use was inversely associated with steatosis grade (p<0.003) and a trend toward less lobular inflammation (p<0.07). After controlling for age, gender, BMI, diabetes mellitus, use of oral insulin-sensitizing agents and non-statin therapy, the use of statins was significantly associated with a 50% decreased risk of having more severe steatosis [adjusted cumulative odds ratio and 95% CI=0.5 (0.3-0.86), p=0.01] and a 45% decreased risk of having more severe lobular inflammation [adjusted cumulative odds ratio and 95% CI=0.55 (0.3-1.0), p=0.047]. No association between use of statins or non-statin lipid-lowering therapy was observed on the grade of portal inflammation, hepatocyte ballooning or fibrosis stage. Conclusion: Use of statins in patients with NAFLD is associated with decreased risk of hepatic steatosis and lobular inflammation. The anti-steatotic and antiinflammatory properties of statins in patients with NAFLD, and in those with chronic liver disease in general, warrant further prospective investigation.

Do Statins Slow Progression of Rheumatic Mitral Stenosis

The pleiotropic anti-inflammatory properties of statins are believed to bring about the slowing in progression of calcific aortic stenosis seen in some previous studies (but not in all; see JW Cardiol Jul 15 2005). In this observational study, investigators examined the effect of …

HMG-CoA Reductase Inhibitors (Statin) Prevents Retinal Neovascularization in a Model of Oxygen-Induced Retinopathy

Retinal neovascularization (RNV) is a primary cause of blindness and involves the dysfunction of retinal capillaries. Recent studies have emphasized the beneficial effects of inhibitors of HMG-CoA reductase (statins) in preventing vascular dysfunction. In the present study, the authors characterized the therapeutic effects of statins on RNV. Statin treatment (10 mg/kg/d fluvastatin) was tested in a mouse model of oxygen-induced retinopathy. Morphometric analysis was conducted to determine the extent of capillary growth. Pimonidazole hydrochloride was used to assess retinal ischemia. Western blot and immunohistochemical analyses were used to assess protein expression levels and immunolocalization. Lipid peroxidation and superoxide radical formation were determined to assess oxidative changes. Fluvastatin treatment significantly reduced the area of the capillary-free zone (P < 0.01), decreased the formation of neovascular tufts (P < 0.01), and ameliorated retinal ischemia. These morphologic and functional changes were associated with statin effects in preventing the upregulation of VEGF, HIF-1 alpha, phosphorylated STAT3, and vascular expression of the inflammatory mediator ICAM-1 (P < 0.01). Superoxide production and lipid peroxidation in the ischemic retina were also reduced by statin treatment (P < 0.01). These data suggest the beneficial effects of statin treatment in preventing retinal neovascularization. These beneficial effects appear to result from the anti-oxidant and anti-inflammatory properties of statins.

Reduction of Heat Shock Protein Antibody Levels by Statin Therapy

Atherosclerosis is a disease whose pathogenesis involves inflammatory and immunological mechanisms, including an autoimmune reaction against heat shock proteins (Hsps). The purpose of this study was to analyze whether the antiatherogenic effect of statin therapy was not limited to its lipid lowering effect, but also included anti-inflammatory and immunomodulatory effects, paying special attention to the measurement of circulating concentrations of anti-Hsp70 and anti-Hsp60 antibodies previously related to vascular disease. Two-hundred and seventy-five subjects aged 40-60 years, randomly selected in an epidemiological study on the incidence of vascular risk factors, were studied. Laboratory tests included a complete lipid profile after a 12-h fast and measurements of glucose, C-reactive-protein, anti-Hsp70 and anti-Hsp60 antibodies. Subjects with hypercholesterolemia had significantly higher concentrations of anti-Hsp70 antibodies as compared to subjects with normal cholesterol concentrations. Statin therapy was associated with 11.63 and 15.3% reductions in total and LDL-cholesterol (P = 0.005 and 0.017, respectively) as compared to untreated subjects, and with lower concentrations of circulating anti-Hsp70 (P = 0.016) antibodies. No differences were found in C-reactive-protein values. Since statin therapy not only reduces lipid profile, but also anti-Hsp70 and anti-Hsp60 antibody concentrations, without changing C-reactive-protein values, it is suggested that such an effect could not be accounted for by the anti-inflammatory properties of statins, but by their direct immunomodulatory properties through their effects on lymphocyte function.

Statins as emerging treatments for asthma and chronic obstructive pulmonary disease

Asthma and chronic obstructive pulmonary disease (COPD) represent increasingly common respiratory conditions with a clear unmet need for more effective and safer therapy. Airway inflammation is key to both asthma pathogenesis and exacerbation of symptoms in COPD. Several lines of evidence are now emerging, demonstrasting that, in addition to their established effectiveness in the treatment of atherosclerotic disease, statins also exhibit anti-inflammatory properties, which may be of relevance for the treatment of chronic lung disease, including asthma and COPD. This review will examine the diverse in vitro and in vivo anti-inflammatory properties of statins and consider the available evidence that statins represent novel therapeutic interventions for asthma and COPD.

Statins attenuate polymethylmethacrylate-mediated monocyte activation

Background Periprosthetic osteolysis precipitates aseptic loosening of components, increases the risk of periprosthetic fracture and, through massive bone loss, complicates revision surgery and ultimately is the primary cause for failure of joint arthroplasty. The anti-inflammatory properties of HMG-CoA reductase inhibitors belonging to the statin family are well recognized. We investigated a possible role for status in initiating the first stage of the osteolytic cycle, namely monocytic activation.Methods We used an in vitro model of the human monocyte/macrophage inflammatory response to poly-methylmethacrylate (PMMA) particles after pretreat-ing cells with cerivastatin, a potent member of the statin family. Cell activation based upon production of TNF-α and MCP-1 cytokines was analyzed and the intracellular Raf-MEK-ERK signal transduction pathway was evaluated using western blot analysis, to identify its role in cell activation and in any cerivastatin effects observed.Results We found that pretreatment with cerivastatin significantly abrogates the production of inflammatory cytokines TNF-α and MCP-1 by human monocytes in response to polymethylmethacrylate particle activation. This inflammatory activation and attenuation appear to be mediated through the intracellular Raf-MEK-ERK pathway.Interpretation We propose that by intervening at the upstream activation stage, subsequent osteoclast activation and osteolysis can be suppressed. We believe that the anti-inflammatory properties of statins may potentially play a prophylactic role in the setting of aseptic loosening, and in so doing increase implant longevity.

Atorvastatin treatment decreases brain Amyloid-β and serum TNF-α levels in Alzheimer’s disease transgenic mice (B214)

Abstract Alzheimer’s Disease (AD) is the most common form of dementia affecting over 14 million elderly worldwide. AD, which has no single cause, is characterized neuropathologically by deposits of Amyloid-β (Aβ) peptides, neurofibrillary tangles, reactive astrocytosis, activation of microglial cells, and deficits in the cholinergic system. Since inflammatory markers are increased markedly in AD brain, it is likely that they participate directly in the destruction of brain cells, and may predict the development of AD years before clinical symptoms appear. Non-steroidal anti-inflammatory drug (NSAID) therapies have shown clinical benefit in treating AD. Likewise, it has been hypothesized that the anti-inflammatory properties of statins may alter AD pathology, independent of their cholesterol lowering effect. In this current study, we treat huAPP R1.40 YAC transgenic mice, a model of Alzheimer’s disease, with therapeutic doses of atorvastatin. Mice either receive a control dose of vehicle, a low dose of atorvastatin or a high dose of atorvastatin via oral gavage. After 12 weeks, animals are sacrificed and levels of Aβ and inflammatory markers, such as IL-1β, IL-6 and TNF-α, were measured. We find that Aβ levels in membrane fractions of the brain are reduced while cytosol fractions show no change. In serum, TNF-α levels decrease with atorvastatin treatment.