Beneficial Effects Of Rosuvastatin Research Articles

Targeting the TLR4/NF-κΒ Axis and NLRP1/3 Inflammasomes by Rosuvastatin: A Role in Impeding Ovariectomy-Induced Cognitive Decline Neuropathology in Rats.

Postmenopausal hormone-related cognitive decline has gained an immense interest to explore the underlying mechanisms and potential therapies. The current work aimed to study the possible beneficial effect of rosuvastatin (ROS) on the cognitive decline induced by ovariectomy in rats. Four groups were used as follows: control group, control + rosuvastatin, ovariectomy, and ovariectomy + rosuvastatin. After sham operation or ovariectomy, rats were given saline or oral dosages of ROS (2mg/kg) every day for 30days. The cognitive functions were assessed using the Morris water maze paradigm, Y-maze test, and new object recognition test. After rat killing, TLR4, caspase-8, and NLRP mRNA expression and protein levels of ASC, AIM2, caspase-1, NLRP1, and PKR were measured in hippocampus. This was complemented by the estimation of tissue content of NF-κΒ, IL-1β, and IL-18 and serum lipid profile quantification. Rosuvastatin showed a promising potential for halting the cognitive impairments induced by estrogen decline through interfering with the TLR4/NF-κΒ/NLRP1/3 axis and inflammasomes activation and the subsequent pyroptosis. This was complemented by the amendment in the deranged lipid profile. Rosuvastatin may exert a beneficial role in attenuating the inflammatory and apoptotic signaling mechanisms associated with postmenopausal cognitive decline. Further investigations are needed to unveil the relationship between deranged plasma lipids and cognitive function.

Short Communication: The Effect of Rosuvastatin on Vascular Disease Differs by Smoking Status in Treated HIV Infection.

Smoking is an important contributor to cardiovascular disease risk and is highly prevalent in the HIV population. In the Stopping Atherosclerosis and Treating Unhealthy Bone with Rosuvastatin in HIV trial (SATURN-HIV), a 96-week, randomized placebo-controlled study testing the effect of rosuvastatin on subclinical vascular disease and immune activation in HIV-infected adults, rosuvastatin improved immune activation and arrested common carotid artery intima media thickness (CCA IMT) progression. In this exploratory analysis, ANOVA was used to test for effect modification by smoking. One-hundred forty-seven adults were included (72 in rosuvastatin group; 75 in placebo group). Groups were similar at baseline. Overall, mean ± SD age was 45.4 ± 9.9 years, 115 (78%) were men and 100 (68%) were African American. Ninety-three (63%) were current smokers (mean ± SD 0.6 ± 0.44 packs/day) and another 24 (16%) were smokers in the past. There were statistically significant randomization group by smoking status interactions for 0-24 (p = .01) and 0-48 (p < .01) week changes in proportion of activated CD4+ T cells and for 0-48 (p < .01) and 0-96 (trend only; p = .06) week changes in CCA IMT. No effect modification by smoking was detected for changes in markers of inflammation or monocyte activation. The beneficial effect of rosuvastatin on CCA IMT was not apparent in smokers although T cell activation improved to a greater degree in this subgroup.

Baseline Vitamin D Deficiency Decreases the Effectiveness of Statins in HIV-Infected Adults on Antiretroviral Therapy.

Vitamin D deficiency is common in HIV. Statins may increase vitamin D, and it is unknown whether vitamin D modifies the effect of statins on cardiovascular disease. SATURN-HIV was a 96-week, randomized, placebo-controlled trial designed to evaluate the effect of rosuvastatin on immune activation and subclinical vascular disease in HIV-infected adults on antiretroviral therapy. This analysis focuses on the prespecified secondary endpoint 25-hydroxyvitamin D [25(OH)D] concentrations. Mixed effects linear modeling and analysis of variance were used to assess the rosuvastatin effect on plasma 25(OH)D concentrations over time and to determine whether baseline vitamin D modifies the rosuvastatin effect on changes in outcomes over the trial. Hundred forty-seven adults were randomized (72 to rosuvastatin and 75 to placebo); 78% were men, 68% African American, with a mean age of 45 years. Baseline 25(OH)D concentrations were similar (overall mean 18 ng/mL) with 65% of participants below 20 ng/mL. Changes in 25(OH)D at 96 weeks were small and not significant within- or between-rosuvastatin and placebo groups. There were significant group by vitamin D status interactions for changes in low-density lipoprotein-cholesterol, proportion of patrolling monocytes expressing tissue factor (CD14dimCD16+TF+), lipoprotein-associated phospholipase A2, and common carotid artery intima media thickness at most time points. For each of these outcomes, the beneficial effects of rosuvastatin were either not apparent or attenuated in participants with 25(OH)D <20 ng/mL. Although 25(OH)D did not change with rosuvastatin, baseline vitamin D deficiency decreased the effectiveness of rosuvastatin. Vitamin D supplementation may be warranted for deficient patients initiating statin therapy.

Relationship between inflammation and benefits of early high-dose rosuvastatin on contrast-induced nephropathy in patients with acute coronary syndrome: the pathophysiological link in the PRATO-ACS study (Protective Effect of Rosuvastatin and Antiplatelet Therapy on Contrast-Induced Nephropathy and Myocardial Damage in Patients With Acute Coronary Syndrome Undergoing Coronary Intervention).

This study sought to investigate whether the beneficial impact of high-dose rosuvastatin against contrast-induced acute kidney injury (CI-AKI) in acute coronary syndrome (ACS) patients varied in relation to baseline high-sensitivity C-reactive protein (hs-CRP) levels. High-dose rosuvastatin administered on admission has been shown to prevent CI-AKI and improve short- and mid-term clinical outcome in ACS patients. All 504 statin-naïve ACS patients enrolled in the PRATO-ACS (Protective Effect of Rosuvastatin and Antiplatelet Therapy on Contrast-Induced Acute Kidney Injury and Myocardial Damage in ACS Patients) study were stratified into baseline hs-CRP tertiles: <2.7 mg/l, ≥2.7 to <7.5 mg/l, and ≥7.5 mg/l. The primary endpoint was CI-AKI occurrence (creatinine ≥0.5 mg/dl or ≥25% above baseline within 72 h). Logistic regression models were used to evaluate the relationship between hs-CRP levels and effects of rosuvastatin. Patients with higher baseline hs-CRP values presented a significantly higher incidence of CI-AKI (5.4%, 8.7%, and 18.3% in the first, second, and third tertiles, respectively; p = 0.0001). The beneficial effect of rosuvastatin was markedly significant in the third hs-CRP tertile (odds ratio: 0.20; 95% confidence interval: 0.07 to 0.54; p = 0.002). Statin-treated patients in the third tertile presented a significantly lower rate of adverse events at 30 days (7.2% vs. 17.4%, p = 0.043) with a trend toward better outcome at 6 months (6.02% vs. 13.04%, p = 0.12). High-dose rosuvastatin administered on admission appears to exert more effective kidney protection in ACS subjects with higher baseline hs-CRP levels resulting in better short- and mid-term clinical outcome. (Protective Effect of Rosuvastatin and Antiplatelet Therapy on Contrast-Induced Nephropathy and Myocardial Damage in Patients With Acute Coronary Syndrome Undergoing Coronary Intervention [PRATO-ACS]; NCT01185938).

Rosuvastatin may reduce the incidence of cardiovascular events in patients with acute coronary syndromes receiving percutaneous coronary intervention by suppressing miR-155/SHIP-1 signaling pathway.

The beneficial effect of rosuvastatin against percutaneous coronary intervention (PCI) related procedural myocardial injury has been determined mostly in patients with acute coronary syndromes (ACS). However, the detailed therapeutic mechanism has not been well studied. Patients with ACS receiving PCI (n = 159) were randomized to control group (placebo treatment) or to rosuvastatin group (20 mg 12 h before PCI, and a further 20 mg 2 h preprocedure dose). Levels of INF-γ, TNF-α, IL-6, miR-155/SHIP-1, and CD4(+)FoxP3(+)Treg in peripheral blood were detected before PCI and 24 h after PCI. Clinical data of these patients were also collected in this prospective study. Compared with placebo, rosuvastatin treatment significantly reduced the incidence of periprocedural myocardial infarction (PMI) and levels of cardiac troponin I (cTnI) associated with decreased relative expression of serum miR-155, levels of inflammatory cytokines (INF-γ, TNF-α, and IL-6), increased SHIP-1 expression and CD4(+)FoxP3(+)Treg percentage values (P < 0.05). In addition, patients with rosuvastatin pretreatment also reduced incidence of 30 days major adverse cardiac events (MACE) compared to the patients with placebo treatment (16 patients vs. 28 patients, P = 0.038). Our study suggests that high loading dose rosuvastatin pretreatment may reduce the incidence of cardiovascular events and levels of inflammatory markers in patients with ACS receiving PCI, which may be explained at least in part, by mechanism involving suppression of miR-155/SHIP-1 signaling pathway.

The beneficial effects of rosuvastatin are independent of zinc supplementation in patients with atherosclerosis

BackgroundStatins have multiple antiatherosclerotic effects, but can reduce blood plasma concentrations of minerals, including zinc. As zinc possesses antiinflammatory and antioxidant effects, low zinc status can promote injuries or inadequate tissue repair in endothelial cells. Metallothionein (MT) expression might modulate responses induced by statins in patients with atherosclerosis. However, research regarding mineral status and the use of statins is scarce. This study evaluated the effects of zinc supplementation on zinc status and expression of the zinc-dependent MT1F and MT2A genes in patients with atherosclerosis treated with rosuvastatin. MethodsA double-blind, randomized clinical trial was performed with 54 participants treated with 10mg rosuvastatin for 4 months with or without zinc supplementation (30mg/day). Diet, lipid profile, high-sensitivity reactive protein C (hs-CRP), plasma and erythrocyte zinc concentrations, erythrocyte superoxide dismutase (SOD) activity, and MT1F and MT2A genes expression were analyzed before and after intervention. ResultsRosuvastatin therapy was effective in reducing low- and non-high-density lipoprotein, total cholesterol, triglycerides, and hs-CRP levels, independent of zinc supplementation. Additionally, zinc treatment had no effect on SOD enzyme activity (P=0.201), plasma (P>0.671) and erythrocyte (P>0.123) zinc concentrations, or the pattern of MT1F and MT2A genes expression (P=0.088 and P=0.229, respectively). ConclusionsThe effectiveness of rosuvastatin treatment is independent of the effects of zinc supplementation. Moreover, rosuvastatin treatment did not have a significant impact on zinc status or MT1F and MT2A genes expression in patients with atherosclerosis.

Valsartan augments the beneficial effect of rosuvastatin with respect to lipid profile, oxidative stress, and the nitric oxide pathway in high-fat diet-induced hypercholesterolemic rats

BackgroundThe renin-angiotensin system contributes considerably to a variety of cardiovascular diseases and is the target of angiotensin receptor blockers (ARBs). Recent studies have reported that in experimental models, as well as some human studies, ARBs had shown the ability to affect lipid metabolism in a modest but significant way. In addition to their primary mode of action, statins and ARBs have common additional properties such as restoration of endothelial activity and antioxidant properties. These properties may potentially aid the improvement treatment of cardiovascular disease.ObjectiveThe present study was designed to evaluate the possible beneficial effects of both therapies valsartan (ARB) and rosuvastatin (3-hydroxy-methylglutaryl coenzyme reductase inhibitor) beyond their blood pressure-lowering and cholesterol-lowering effects, and the possibility that valsartan may enhance the beneficial effects of rosuvastatin in high-fat diet-induced hypercholesterolemic (HC) rats with respect to lipid profile, oxidative stress, and the nitric oxide pathway.Materials and methodsHC was induced in male albino Wistar rats by a daily gavage of a cocktail containing 1 l peanut oil, 100 g cholesterol, and 100 g cholic acid over a period of 21 days. These animals were assigned randomly to the following groups: HC, HC/rosuvastatin, HC/valsartan, and HC/rosuvastatin+valsartan.ResultsDaily gavage of the cocktail for 3 weeks induced a significant increase in plasma total cholesterol (TC), triglyceride (TG), and low-density lipoprotein and a significant reduction in high-density lipoprotein (HDL), but did not induce any significant changes in arterial blood pressure and heart rate. Meanwhile, the plasma nitric oxide level was reduced to 17.49% of its normal level and the plasma malondialdehyde level was significantly increased by 32.53%. Coadministration of valsartan with rosuvastatin normalized plasma HDL, significantly decreased plasma TC and low-density lipoprotein to a greater extent than monotherapy with each drug as well as ameliorated the effect of HC diet on the plasma TG level in HC rats. Moreover, the combined treatment induced a significant increase in the plasma nitrate+nitrite level compared with the corresponding HC value and normalized the plasma malondialdehyde level with respect to the effect of rosuvastatin or valsartan alone. In addition, histopathological and morphometric studies of the aorta and liver showed marked improvement after combined treatment with rosuvastatin and valsartan when compared with the HC group.ConclusionConclusively, coadministration of rosuvastatin and valsartan in high-fat diet-induced HC rats conferred a greater degree of protection as it ameliorated the increase in the plasma TC and TG and restored HDL to its normal value, improved the endothelial function, and reduced oxidative stress, together with improvement in the histopathological features in rats that had previously received a high-fat diet.

Beneficial Effects of Rosuvastatin in Heart of C57Bl/6 Mice with Diet- Induced Metabolic Syndrome - A Preliminary Study

Background: There is a significant association between the prevalence of cardiovascular disease and metabolic syndrome. Evidence shows that obesity is associated with structural and functional changes in the heart. Estatin drugs can reduce the endogenous synthesis of cholesterol and possess properties that are independent of their effects on lipids, the so-called pleiotropic effects. The present work aims to study the effects of rosuvastatin on the heart of mice with diet-induced metabolic syndrome, such as tissue remodeling and ultrastructural changes. Methods: In this work we studied the effects of rosuvastatin treatment on the body mass, blood lipids, blood pressure, cardiac remodeling and structure, as well as the ultrastructural changes on the heart of the C57BL/6 male mice fed with a high-fat diet. Results: The rosuvastatin treatment reduced levels of blood lipids, blood pressure and body mass of high-fat mice. Furthermore, the cardiac remodeling was attenuated, with a decrease of the interstitial and perivascular fibrosis and the preservation of the integrity of mitochondrial morphology. Conclusion: Thus, our work concludes that rosuvastatin has a beneficial effect on the heart of C57Bl/6 mice fed high fat diet being an important tool in the treatment and/or on the prevention of heart disease.

Rosuvastatin Alleviates Diabetic Cardiomyopathy by Inhibiting NLRP3 Inflammasome and MAPK Pathways in a Type 2 Diabetes Rat Model

Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is important in inflammation of several diabetic complications. However, the potential role of NLRP3 inflammasome in the inflammatory process of diabetic cardiomyopathy (DCM) remains unclear. Although rosuvastatin (RSV) has an anti-inflammatory effect on some cardiovascular diseases, its influence on DCM is incompletely understood. We aimed to explore the effect on and underlying mechanism of RSV in DCM, and whether NLRP3 is a target for RSV. Type 2 diabetes was induced in rat. The characteristics of type 2 DCM were evaluated by metabolic tests, echocardiography and histopathology. The expression of factors was determined by real-time RT-PCR and western blot. Eight-week RSV treatment and NLRP3 gene silencing were used to investigate the effect and underlying target of RSV in DCM. Compared with controls, diabetic rats showed severe metabolic disorder, cardiac dysfunction, fibrosis, disorganized ultrastructure, and excessive activation of thioredoxin interacting/inhibiting protein (TXNIP, p < 0.05), NLRP3 inflammasome (NLRP3, p < 0.01; apoptosis-associated speck-like protein containing a caspase recruitment domain [ASC], p < 0.05; caspase-1, p < 0.01), interleukin-1β (p < 0.01) and mitogen-activated protein kinases (MAPKs, all p < 0.01). Compared with diabetes alone, RSV ameliorated the overexpression of NLRP3 inflammasome (NLRP3, p < 0.05; ASC, p < 0.05; pro-caspase-1 p < 0.05, caspase-1 p20, p < 0.01) and MAPKs (all p < 0.05), which paralleled the cardiac protection of RSV. Silencing NLRP3 ameliorated cardiac remodeling and dysfunction. The beneficial effects of RSV in vehicle-treated rats were all abrogated in NLRP3-silenced rats. The beneficial effect of RSV on DCM depended on inhibited NLRP3 inflammasome, and correlated with suppression of the MAPKs.

Beneficial effects of rosuvastatin on insulin resistance, adiposity, inflammatory markers and non-alcoholic fatty liver disease in mice fed on a high-fat diet

The aim of the present study was to evaluate the effects of ST (rosuvastatin) and GZ (rosiglitazone) on IR (insulin resistance) and on liver as well as adipose tissue in mice fed on an HF (high-fat) diet. Our data show that treatment with ST resulted in a marked improvement in insulin sensitivity characterized by enhanced glucose clearance during the insulin tolerance test and a 70% decrease in the HOMA-IR (homoeostasis model assessment of insulin resistance) index level (P=0.0008). The ST-treated mice exhibited lower gains in BM (body mass; -8%; P<0.01) and visceral fat pad thickness (-60%; P<0.01) compared with the untreated HF group. In comparison with HF-diet-fed mice, HF+ST-treated mice showed a significant reduction in hepatomegaly and liver steatosis (-6%, P<0.05; and -21%, P<0.01 respectively). In HF+ST-treated mice, the hepatic TAG (triacylglycerol) levels were reduced by 58% compared with the HF group (P<0.01). In addition, the expression of SREBP-1c (sterol-regulatory-element-binding protein-1c) was decreased by 50% in the livers of HF+ST-treated mice (P<0.01) relative to the HF-diet-fed mice. The levels of resistin were lower in the HF+ST-treated group compared with the HF group (44% less, P< 0.01). In conclusion, we demonstrated that ST treatment improved insulin sensitivity and decreased liver steatosis in mice fed on an HF diet. Furthermore, ST reduced BM gains, improved the circulating levels of plasma cholesterol and TAG, and reduced hepatic TAG, which was concomitant with lower resistin levels.

Rosuvastatin beneficially alters the glomerular structure of kidneys from spontaneously hypertensive rats (SHRs)

The incidence of chronic renal diseases is increasing worldwide, and there is a great need to identify therapies capable of arresting or reducing disease progression. The current treatment of chronic nephropathies is limited to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, but increasing clinical and experimental evidence suggests that statins could play a therapeutic role. Ultrastructural studies have shown the presence of gap junctions within all the cells of the glomerulus and podocytes have been found to contain primarily connexin-43. The present study aims to observe the beneficial effects of rosuvastatin on structural and ultrastructural renal morphology and on glomerular connexin-43 expression in normotensive rats and spontaneously hypertensive rats (SHR). Rats were randomly allocated into four groups: WKY-C: normotensive animals no receiving rosuvastatin; WKY-ROS: normotensive animals receiving rosuvastatin; SHR-C: hypertensive animals no receiving rosuvastatin; SHR-ROS: hypertensive animals receiving rosuvastatin. Our results show no differences in blood urea, creatinine, uric acid and creatine phosphokinase levels between the groups, however, there was an decreasing of 24-h protein excretion in SHR-ROS. Capsular area in SHR-ROS was decreased, however, there was no alteration in urinary space. By transmission electron microscopy the slit diaphragm and podocyte foot processes were more preserved in SHR-ROS. By scanning electron microscopy the podocyte foot processes were more preserved in SHR-ROS. Increased connexin-43 immunofluorescence was observed in glomeruli of WKY-ROS and SHR-ROS. In conclusion, we hypothesize that renal pleiotropic effect of rosuvastatin can be a therapeutic tool for improving kidney ultrastructure and, consequently, renal function in hypertensive individuals.

Beneficial effects of rosuvastatin on aortic adverse remodeling in nitric oxide-deficient rats

This study aimed to evaluate the effect of rosuvastatin upon structural and ultrastructural aortic remodeling in a rat model of hypertension induced by NO synthase blockade. Wistar rats were divided into 4 groups: Control group (C); control treated with rosuvastatin 20 mg/kg/day (CR); L-NAME group 40 mg/kg/day (LN) and L-NAME treated with rosuvastatin (LNR) (same doses). Body mass and blood pressure were measured weekly; the experiment lasted 5 weeks. L-NAME administration augmented blood pressure (BP) in the LN group in comparison to the C group (123.3 vs. 180.5 mmHg at week 5). In LNR rats, rosuvastatin slightly attenuated BP rise, but it had no effect on the BP of CR group. Intima and media thickening of the thoracic aorta were observed in the LN group, and increased elastic fiber content as well. Rosuvastatin prevented all these alterations as seen in the LNR group. Ultrastructural changes due to L-NAME intake (intracellular vesicles and altered membrane morphology in endothelial cells, extracellular matrix deposition, and cytoplasmatic projections from smooth muscle cells toward the internal elastic lamina) were also prevented by rosuvastatin. All in all, rosuvastatin administration is capable of attenuating ultrastructural aortic wall remodeling in NO-deficient rats despite small changes in blood pressure.

Rosuvastatin Prevents Conduit Artery Endothelial Dysfunction Induced by Ischemia and Reperfusion by a Cyclooxygenase-2–Dependent Mechanism

The purpose of this study was to determine whether single-dose rosuvastatin (40 mg) protects against ischemia and reperfusion (IR)-induced endothelial dysfunction in humans and whether this effect is cyclooxygenase (COX)-2 dependent. Animal studies have demonstrated that rosuvastatin can limit damage and improve recovery after IR. In a double-blind, parallel design, 20 volunteers were randomized to a single dose of oral rosuvastatin (40 mg) or placebo. Twenty-four hours later, endothelium-dependent, flow-mediated dilation (FMD) of the radial artery was measured before and after IR (15 min of upper arm ischemia followed by 15 min of reperfusion). In a separate protocol, 18 volunteers received the COX-2 inhibitor celecoxib (200 mg orally twice daily) for 5 days. On day 4, subjects were randomized to single-dose rosuvastatin (40 mg) or placebo and 24 h later underwent the same protocol as described. Pre-IR FMD was similar between groups (p = NS). IR significantly blunted FMD in the placebo group (FMD pre-IR: 6.4 +/- 1.4%; FMD post-IR: 1.1 +/- 3.8%, [p = 0.002]). Rosuvastatin prevented this impairment (FMD pre-IR: 7.5 +/- 3.1%; FMD post-IR: 6.2 +/- 3.9%, [p = NS] vs. rosuvastatin pre-IR, [p = 0.03] vs. placebo). Pre-treatment with celecoxib completely abolished rosuvastatin's protective effect (FMD pre-IR: 8.0 +/- 2.2%; FMD post-IR: 1.4 +/- 2.0%, [p < 0.001] compared with pre-IR, [p = NS] vs. placebo, [p = 0.002] vs. rosuvastatin alone). Rosuvastatin pharmacologically prevents the development of IR-induced conduit artery endothelial dysfunction. This beneficial effect of rosuvastatin is mediated by a COX-2-dependent mechanism, evidence that may also provide potential mechanistic insight into the reported cardiotoxic effects of COX-2 inhibitors.

Abstract 5521: Rosuvastatin Prevents Ischemia and Reperfusion-Induced Endothelial Dysfunction by a COX-2 Dependent Mechanism

BACKGROUND: Animal studies have demonstrated that rosuvastatin (RSV) can limit the damage induced by ischemia-reperfusion (IR) in the cardiac, cerebral and mesenteric circulation. It remains unknown whether this beneficial effect of RSV can also be demonstrated in humans, and by what mechanism this may occur. METHODS AND RESULTS: Twenty healthy volunteers were randomized to a single dose of oral RSV (40 mg) or placebo. 24 hours later, endothelium-dependent, flow-mediated dilation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). There was no difference in pre-IR FMD between groups (P=NS). In the placebo group, FMD was significantly blunted after IR (FMD pre-IR: 6.4+/−0.4%, post-IR: 1.1+/−1.2%, P&lt;0.01). This impairment in FMD with IR was prevented with RSV (Table ; FMD before IR: 7.5+/−1.0%; after IR: 6.2+/−1.2%, P =NS compared with RSV before IR; P&lt;0.05 vs. placebo). In a separate protocol, 18 healthy volunteers received the cyclooxygenase-2 (COX-2) inhibitor celecoxib (200mg BID p.o.) for 5 days. On day 4, subjects were randomized to a single dose of RSV (40mg) or placebo and 24 hours later underwent the same protocol as above. Pretreatment with celecoxib completely abolished RSV’s protective effect (Table ; FMD pre-IR: 8.0±2.2%, post-IR: 1.4±2.0%, P&lt;0.001 before versus after IR, P=NS vs. placebo). IR did not modify resting arterial diameter, baseline blood flow or peak hyperemic blood flow during FMD in either protocol (Table ; P=NS for all). CONCLUSIONS: The present findings demonstrate, for the first time in humans, the ability of RSV to pharmacologically prevent the development of IR-induced endothelial dysfunction. In addition, these data demonstrate the importance of COX-2 in the manifestation of this preconditioned phenotype, evidence that also provides potential mechanistic insight into the observed cardiovascular toxicity with COX-2 inhibitors.

Beneficial effect of rosuvastatin on cardiac dysfunction is associated with alterations in calcium‐regulatory proteins

The normal expression of Ca(2+)-regulatory protein is critical for efficient myocardial function. The present study tested the hypothesis that rosuvastatin treatment may attenuate left ventricular (LV) remodelling and dysfunction in the failing heart, which may be associated with alterations of Ca(2+)-regulatory protein. We investigated the change of LV remodelling and function in a rat model of cardiac dysfunction due to myocardial infarction (MI) with or without rosuvastatin (10 mg/kg/day) treatment for 10 weeks. The protein expression of sarcoplasmic reticulum Ca(2+) ATPase (SERCA)2a, phospholamban (PLB), and phospho-PLB at serine-16 (pSer16-PLB), as well as SERCA activity, interleukin (IL)-6, and IL-10 levels were evaluated. After rosuvastatin treatment, LV remodelling and dysfunction were prevented. Rosuvastatin prevented the decrease of SERCA2a and pSer16-PLB expression, increased SERCA activity, but showed no effect on PLB expression. Furthermore, rosuvastatin reduced the increased IL-6 level and further elevated IL-10 level in the peri-infarct and remote zones of MI. Serum lipid levels remained unchanged. Rosuvastatin is effective in preventing LV remodelling and dysfunction in the failing heart. The molecular mechanism may be related to normalization of SERCA2a expression, SERCA activity, and pSer16-PLB levels, as well as through cytokine alterations independent of its lipid-lowering effect.

Effect of rosuvastatin on capillary filtration of albumin and blood pressure in rats with streptozotocin-induced diabetes

An increase in capillary filtration of albumin (CFA) is well demonstrated in diabetes. Statins may exert a protective effect against endothelial dysfunction. The aim of this study was to test whether rosuvastatin may prevent the increase in peripheral CFA in diabetic rats and the role of blood pressure lowering. Rats with streptozotocin-induced diabetes were randomized to receive either rosuvastatin 20 mg/kg/d (group R) or both rosuvastatin 20 mg/kg/d and mevalonate 20 mg/kg/d (group RM) or no treatment (group U). CFA index was measured on a limb by a non-invasive isotopic test using technetium-labelled albumin, at three time points: at mean age of 3 months, before treatment; at 5 and 8 months, i.e. after 2 and 5 months of treatment. At 3 months, interstitial albumin retention (AR) was markedly increased in the 3 groups. From 3 to 5 months, AR increased significantly in group U, decreased in group R and in group RM. At 5 and 8 months, AR was significantly lower in groups R and RM than in group U. Systolic blood pressure (SBP) was measured at 8 months and was significantly lower in group R than in group U and RM. At 8 months, serum cholesterol levels were not different between the three groups whereas triglycerides were significantly lower in groups R and RM than in group U. In conclusion, in diabetic rats rosuvastatin prevents the increase in peripheral CFA and induces a decrease in blood pressure. The beneficial effect of rosuvastatin on endothelial function does not seem to result from blood pressure reduction nor lipid lowering effects.

The GALAXY Program: an update on studies investigating efficacy and tolerability of rosuvastatin for reducing cardiovascular risk

The GALAXY Program is a series of clinical studies investigating the efficacy and tolerability of rosuvastatin in line with the hypothesis that the statin with the greatest efficacy for improving the atherogenic lipid profile and beneficially modifying inflammatory markers will also slow progression of atherosclerosis and improve cardiovascular outcomes. Completed studies report that rosuvastatin is more effective than comparator statins in reducing low-density lipoprotein cholesterol, improving the lipid profile and enabling patients to achieve lipid goals, including revised, more stringent goals, even in high-risk patients. Studies have also reported that rosuvastatin can arrest and even regress atherosclerosis. Ongoing outcomes studies will determine whether these beneficial effects of rosuvastatin translate into reduced morbidity and mortality.

Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels

Patients with combined hyperlipidemia and low high-density lipoprotein (HDL) cholesterol levels may benefit from combination therapy with a statin and niacin; therefore, we assessed the efficacy and safety of rosuvastatin and extended-release (ER) niacin alone and in combination in 270 patients with this atherogenic dyslipidemia. Men and women ≥18 years with fasting total cholesterol levels ≥200 mg/dl, triglycerides 200 to 800 mg/dl, apolipoprotein B ≥110 mg/dl, and HDL cholesterol <45 mg/dl were randomized to 1 of 4 treatments in this 24-week, open-label, multicenter trial: rosuvastatin 10 to 40 mg; ER niacin 0.5 to 2 g; rosuvastatin 40 mg/ER niacin 0.5 to 1 g; or rosuvastatin 10 mg/ER niacin 0.5 to 2 g. Percent changes from baseline in low-density lipoprotein (LDL) cholesterol, non-HDL cholesterol, and other lipid measurements at week 24 were determined by analysis of variance, with statistical testing performed separately between the rosuvastatin monotherapy group and each remaining treatment group. Daily doses of rosuvastatin 40 mg reduced LDL and non-HDL cholesterol significantly more than either ER niacin 2 g or rosuvastatin 10 mg/ER niacin 2 g (−48% vs −0.1% and −36% for LDL cholesterol and −49% vs −11% and −38% for non-HDL cholesterol, respectively; p <0.01 for all comparisons); no additional reduction in LDL or non-HDL cholesterol was observed with the combination of rosuvastatin 40 mg/ER niacin 1.0 g (−42% and −47%; p = NS). Triglyceride reductions ranged from −21% (ER niacin monotherapy) to −39% (rosuvastatin 40 mg/ER niacin 1 g), but no observed differences were statistically significant. Compared with rosuvastatin alone, rosuvastatin 10 mg/ER niacin 2 g produced significantly greater increases in HDL cholesterol (11% vs 24%, p <0.001) and apolipoprotein A-I (5% vs 11%, p <0.017). Similar increases in HDL cholesterol and apolipoprotein A-I were noted between the monotherapy groups. Over 24 weeks, rosuvastatin alone was better tolerated than either ER niacin alone or the combinations of rosuvastatin and ER niacin.