Influence Of Statins Research Articles

Influence of statin use on progression of postoperative fatty infiltration in the arthroscopic rotator cuff repair.

The purpose of this study was to determine the influence of hyperlipidemia and statin (hydroxyl-methylglutaryl-coenzyme-A reductase inhibitors) use on fatty infiltration (FI) of the rotator cuff muscle after arthroscopic rotator cuff repair (ARCR). The presence or absence of statin use and type of statins used (type 1 naturally derived statins and type 2 synthetic statins) were examined. This was a retrospective review of 620 cases (620 shoulders) who underwent arthroscopic rotator cuff repair. Total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG) levels, and statin use were reviewed with the medical records. FI of the cuff muscles and repair integrity were assessed by MRI. A generalized linear model was used to analyze the progression of fatty infiltration. Repair integrity was determined according to the Sugaya classification, with types 4 and 5 as retears. The mean age was 66.9 years (272, females). The overall retear rate was 16.1%. There was no significant difference in retears between statin use and non-use with a trend toward higher retear rates in the type 2 statins. FI progressed postoperatively, and multivariate regression showed that type 2 statin use was a significant risk factor (p = 0.006). Other significant risk factor were large-to-massive tear (p = 0.02) and retear (p < .0001). The progression of FI after ARCR was observed. The new generation of strong statins (type 2 statins) was a significant risk factor for the progression of postoperative fatty infiltration, while neither serum lipid level (TC, LDL, and TG) was significant.

Simvastatin exerts neuroprotective effects post-stroke by ameliorating endoplasmic reticulum stress and regulating autophagy/apoptosis balance through pAMPK/LC3B/ LAMP2 axis

Statins have evident neuroprotective role in acute ischemic stroke(AIS). The pleiotropic effect by which statin exerts neuroprotective effects, needs to be explored for considering it as one of the future adjunctive therapies in AIS. Endoplasmic reticulum(ER) assists cellular survival by reducing protein aggregates during ischemic conditions. ER-stress mediated apoptosis and autophagy are predominant reasons for neuronal death in AIS. Statin exerts both anti-apoptotic and anti-autophagic effect in neurons under ischemic stress. Although the influence of statin on autophagic neuroprotection has been reported with contradictory results. Thus, in our study we have attempted to understand its influence on autophagic protection while inhibiting upregulation of autophagic death(autosis). Previously we reported, statin can alleviate apoptosis via modulating cardiolipin mediated mitochondrial dysfunction. However, the clearance of damaged mitochondria is essential for prolonged cell survival. In our study, we tried to decipher the mechanism by which statin leads to neuronal survival by the mitophagy mediated cellular clearance. Simvastatin was administered to Sprague Dawley(SD) rats both as prophylaxis and treatment. The safety and efficacy of the statin was validated by assessment of infarct size and functional outcome. A reduction in oxidative and ER-stress were observed in both the prophylactic and treatment groups. The influence of statin on autophagy/apoptosis balance was evaluated by molecular assessment of mitophagy and cellular apoptosis. Statin reduces the post-stroke ER-stress and predominantly upregulated autophagolysosome mediated mitophagy than apoptotic cell death by modulating pAMPK/LC3B/LAMP2 axis. Based on the above findings statin could be explored as an adjunctive therapy for AIS in future.

Influence of Statins and Fibrates Drugs on Bone Health and Regeneration

Influence of Statins and Fibrates Drugs on Bone Health and Regeneration

P119 - Influence of statins in mCRPC patients treated with new antiandrogen therapies

P119 - Influence of statins in mCRPC patients treated with new antiandrogen therapies

Some pleiotropic effects of statins on hepatocellular carcinoma cells: Comparative study on atorvastatin, rosuvastatin and simvastatin

PurposeFor many years, statins have been the most commonly used drugs in cholesterol-lowering therapy. In addition to these therapeutic effects, statins exhibit other, pleiotropic effects that can be beneficial, but also harmful to cells and tissues. The aim of this research was to determine and compare the pleiotropic effects of structurally different statins: atorvastatin, simvastatin and rosuvastatin at different concentrations on hepatocellular carcinoma (HepG2) cells. Materials and methodsThe MTT assay was used to determine the cytotoxic effects of statins. The influence of statins on the production of reactive oxygen species (ROS) was determined by measuring fluorescent response of 2,7-dichlorofluorescein diacetate (DCFH-DA). The effect of statins on glucose production and excretion was determined with glucose production assay. ResultsThe obtained results confirmed that all tested statins exhibit cytotoxic effects, increase the production of ROS as well as the production and excretion of glucose from HepG2 cells. It was observed that all the mentioned effects are more pronounced with lipophilic statins, atorvastatin and simvastatin compared to hydrophilic rosuvastatin. ConclusionThe less pronounced pleiotropic effects of rosuvastatin on HepG2 cells are probably due to differences in structure and solubility compared to atorvastatin and simvastatin. Transporter-dependent and a slower influx of rosuvastatin into cells compared to the tested lipophilic statins probably lead to a weaker accumulation of rosuvastatin in HepG2 cells, which results in less pronounced pleiotropic effects compared to lipophilic atorvastatin and simvastatin.

Statins influence the relationship between ATP-binding cassette A1 membrane transporter-mediated cholesterol efflux capacity and coronary atherosclerosis in rheumatoid arthritis

ObjectivesCholesterol efflux capacity (CEC) is the main antiatherogenic function of high-density lipoprotein (HDL). ATP-binding-cassette A1 (ABCA1) membrane transporter initiates cholesterol export from arterial macrophages to pre-β HDL particles fostering their maturation; in turn, those accept cholesterol through ABCG1-mediated export. Impaired pre-β HDL maturation may disrupt the collaborative function of the two transporters and adversely affect atherosclerosis. Statins exert atheroprotective functions systemically and locally on plaque. We here evaluated associations between ABCA1-CEC, coronary atherosclerosis and cardiovascular risk and the influence of statins on those relationships in rheumatoid arthritis (RA). MethodsEvaluation with computed tomography angiography was undertaken in 140 patients and repeated in 99 after 6.9 ± 0.3 years. Events comprising cardiovascular death, acute coronary syndromes, stroke, claudication, revascularization and heart failure were recorded. ABCA1-CEC and ABCG1-CEC were evaluated in J774A.1 macrophages and Chinese hamster ovary (CHO) cells respectively and expressed as percentage of effluxed over total intracellular cholesterol. Covariates in all cardiovascular event risk and plaque outcome models included atherosclerotic cardiovascular disease (ASCVD) risk score and high-density lipoprotein cholesterol. ResultsABCA1-CEC negatively correlated with ABCG1-CEC (r = −0.167, p = 0.049). ABCA1-CEC associated with cardiovascular risk (adjusted hazard ratio 2.05 [95%CI 1.20–3.48] per standard deviation [SD] increment). There was an interaction of ABCA1-CEC with time-varying statin use (p = 0.038) such that current statin use inversely associated with risk only in patients with ABCA1-CEC below the upper tertile. ABCA1-CEC had no main effect on plaque or plaque progression; instead, ABCA1-CEC (per SD) associated with fewer baseline total plaques (adjusted rate ratio [aRR] 0.81, [95%CI 0.65–1.00]), noncalcified plaques (aRR 0.78 [95%CI 0.61–0.98]), and vulnerable low-attenuation plaques (aRR 0.41 [95%CI 0.23–0.74]) in statin users, and more low-attenuation plaques (aRR 1.91 [95%CI 1.18–3.08]) in nonusers (p-for-interaction = 0.018, 0.011, 0.025 and < 0.001 respectively). Moreover, ABCA1-CEC (per SD) associated with greater partially/fully-calcified plaque progression (adjusted odds ratio 3.07 [95%CI 1.20–7.86]) only in patients not exposed to statins during follow-up (p-for-interaction = 0.009). ConclusionIn patients with RA, higher ABCA1-CEC may reflect a proatherogenic state, associated with enhanced cardiovascular risk. Statin use may unmask the protective impact of ABCA1-mediated cholesterol efflux on plaque formation, progression and cardiovascular risk.

Metabolic and structural changes in the myocardium of rats with hypercholesterolemia after prolonged administration of simvastatin

BACKGROUND: The use of statins in cardiovascular pathologies in some cases is associated with the risk of developing statin-induced myopathy, the mechanisms of which are not fully understood. Only a few studies of molecular changes in the myocardium in statin myopathy are presented in the literature. However, the myocardium, as a type of muscle tissue, can also be involved in the pathological process. In this regard, in our opinion, it is advisable to analyze the biochemical changes in the rat myocardium against the background of the use of simvastatin.&#x0D; AIM: To analysis of the dynamics of changes in the end products of glycolysis and the isoform composition of the giant protein titin in the heart muscle in animals with experimental hypercholesterolemia on the background of long-term administration of simvastatin.&#x0D; MATERIALS AND METHODS: The study was carried out on outbred male rats divided into 3 groups: control group (35 individuals) intact animals; comparison group (35 animals) intact animals treated with simvastatin for two months; experimental group divided into: subgroup 1 (35 individuals) animals with induced alimentary hypercholesterolemia, subgroup 2 (35 individuals) animals with induced alimentary hypercholesterolemia, which were administered simvastatin for two months. During the experiment, the content of the giant sarcomere protein titin, as well as changes in the concentration of pyruvate and lactic acid in the myocardium of the animals of the studied groups were studied.&#x0D; RESULTS: In animals with a physiological course of metabolic processes, the administration of simvastatin caused the accumulation of lactic acid in the myocardium. Under conditions of alimentary hypercholesterolemia under the influence of simvastatin, a decrease in the elevated level of pyruvate and lactic acid was revealed, which is obviously due to a decrease in pathobiochemical shifts in energy metabolism. The determination of the isoform composition of titin made it possible to establish that the administration of simvastatin under conditions of alimentary hypercholesterolemia contributed to the appearance of early dystrophic changes in the myocardium, which is consistent with the results of earlier studies of impaired myocardial contractile activity under the influence of statins.&#x0D; CONCLUSIONS: The results obtained indicate the need for a more thorough study of statins in terms of their safe use in patients with cardiovascular pathology.

Statins Lower Lipid Synthesis But Promote Secretion of Cholesterol-Enriched Extracellular Vesicles and Particles.

Lipid droplets are lipid-rich cytosolic organelles that play roles in cell signaling, membrane trafficking, and many other cellular activities. Recent studies revealed that lipid droplets in cancer cells have various biological functions, such as energy production, membrane synthesis, and chemoresistance, thereby fostering cancer progression. Accordingly, the administration of antilipemic agents could improve anti-cancer treatment efficacy given hydrophobic chemotherapeutic drugs could be encapsulated into lipid droplets and then expelled to extracellular space. In this study, we investigated whether statins could promote treatment efficacy of lipid droplet-rich ovarian SKOV-3 cells and the potential influences on generation and composition of cell-derived extracellular vesicles and particles (EVP). Our studies indicate that statins can significantly lower lipid biosynthesis. Moreover, statins can inhibit proliferation, migration, and invasion of SKOV-3 cells and enhance chemosensitivity in vitro and in vivo. Furthermore, statins can lower EVP secretion but enforce the release of cholesterol-enriched EVPs, which can further lower lipid contents in parental cells. It is the first time that the influence of statins on EVP generation and EVP-lipid composition is observed. Overall, we demonstrated that statins could inhibit lipid production, expel cholesterol to extracellular space via EVPs, and improve chemosensitivity.

Influence of statins in metastatic castration-resistant prostate cancer patients treated with new antiandrogen therapies: a systematic review and meta-analysis.

ABSTRACTObjective To evaluate whether the addition of statins to the new antiandrogens (enzalutamide or abiraterone) affects overall survival in patients with metastatic castration-resistant prostate cancer.Methods We searched studies in English language including the keywords statins, overall survival, and metastatic castration-resistant prostate cancer, at PubMed® (MEDLINE®), Embase and Cochrane databases.Results A total of 195 articles were initially identified, but only four met the inclusion criteria and were selected for the meta-analysis. A total of 955 patients, 632 on the new antiandrogens only group, and 323 on the new antiandrogens + statins group, were analyzed. In all four studies the combination therapy (new antiandrogens + statin) was well tolerated, regardless of which new antiandrogens were used. Neither the type of statin nor the doses and duration of use were well specified in the studies. The combination therapy in metastatic castration-resistant prostate cancer was associated with an overall survival improvement, and a 46% reduction in death (hazard ratio of 0.54; 95%CI 0.34-0.87; p<0.01) in multivariate analysis.Conclusion There seems to be a clinical benefit with the association of statins to the new antiandrogens in patients with metastatic castration-resistant prostate cancer, suggesting longer overall survival with no important collateral effect. However, due to fragility of the studies available in the literature, we are not yet capable of recommending this combination of drugs in the clinical practice. Further randomized prospective studies are warranted to confirm these beneficial outcomes.

The impact of statins on wound healing: an ally in treating the highly comorbid patient.

To identify the impact that HMG-CoA reductase inhibitors (statins) use has on wound healing outcomes in patients with comorbidities. A retrospective chart review evaluating all new patients presenting to our tertiary wound care centre in 2013 with lower extremity wounds. Patients were divided into two groups depending on whether they took statins or not. Data on wound healing outcomes and wound/patient characteristics were collected. Primary outcomes included healing rate and progression to complete wound healing. Patients were excluded if they had incomplete data or were lost to follow-up before healing status could be confirmed. A total of 194 patients met the inclusion criteria and were allocated to either the statin group (n=89) or to the non-statin group (n=105). Median initial wound size was 0.6cm3 (Interquartile range (IQR): 0.15-2.4) (p=0.684). In the statin group, 54 (60.6%) patients progressed to complete wound healing compared with 47 (44.7%) in the non-statin group (p=0.027). Median rate of wound healing was 6.7×10-3cm3/day (IQR: 1.5×10-3-2.6×10-2) compared with 3.8×10-3cm3/day (IQR: 1.7×10-3-1.3×10-2) in the non-statin group (p=0.773). Increased age and a higher number of comorbidities were reported in the statin group (p<0.001), respectively). A total of seven patients required amputation: five patients in the statin group and two patients in the non-statin group (p=0.250). This study revealed increased progression to wound healing in patients who were taking statins. The influence of statins on wound healing is promising, but future trials are needed to justify use of this medication class independent of cardiovascular benefit and exclusively for wound healing.

Individual Response to Radiation of Individuals with Neurofibromatosis Type I: Role of the ATM Protein and Influence of Statins and Bisphosphonates.

Neurofibromatosis type 1 (NF1) is a disease characterized by high occurrence of benign and malignant brain tumours and caused by mutations of the neurofibromin protein. While there is an increasing evidence that NF1 is associated with radiosensitivity and radiosusceptibility, few studies have dealt with the molecular and cellular radiation response of cells from individuals with NF1. Here, we examined the ATM-dependent signalling and repair pathways of the DNA double-strand breaks (DSB), the key-damage induced by ionizing radiation, in skin fibroblast cell lines from 43 individuals with NF1. Ten minutes after X-rays irradiation, quiescent NF1 fibroblasts showed abnormally low rate of recognized DSB reflected by a low yield of nuclear foci formed by phosphorylated H2AX histones. Irradiated NF1 fibroblasts also presented a delayed radiation-induced nucleoshuttling of the ATM kinase (RIANS), potentially due to a specific binding of ATM to the mutated neurofibromin in cytoplasm. Lastly, NF1 fibroblasts showed abnormally high MRE11 nuclease activity suggesting a high genomic instability after irradiation. A combination of bisphosphonates and statins complemented these impairments by accelerating the RIANS, increasing the yield of recognized DSB and reducing genomic instability. Data from NF1 fibroblasts exposed to radiation in radiotherapy and CT scan conditions confirmed that NF1 belongs to the group of syndromes associated with radiosensitivity and radiosusceptibility.

Influence of statins on cartilage homeostasis after traumatic impact and during chondrocyte re-differentiation

Influence of statins on cartilage homeostasis after traumatic impact and during chondrocyte re-differentiation

Abstract PS11-12: Statin use significantly improves outcome in luminal B relative to luminal A breast cancers

Abstract Cholesterol and statins may have a role in breast cancer progression where statins have been found to associate with reduced breast cancer recurrence risk in early breast cancer patients. Links between breast cancer progression and intra-tumoural cholesterol metabolism have been described, indicating possible underlying cancer biology. Here we set out to explore whether statin use correlated with differences in baseline tumour characteristics including biological tumour sub-type and whether outcomes were impacted by statin use, both overall and within sub-types. Two cohorts of invasive breast cancer patients from a single institution in Western Australia were studied; one comprised of cases across all sub-types (n=417) and one of hormone receptor positive cases only (n=1766), with available data on tumour biology, statin use, and relapse. Statin prescription data was available on 2183 patients, of whom 454 were taking a statin at some point from diagnosis through the end of the follow-up period. Of the patients where statin type was known, 38% were taking a hydrophilic and 62% a lipophilic statin. Although tumour stage did not vary by statin usage, those on a statin had less frequent high grade tumours (12.7 v 18.7%, p=0.025), and were more frequently estrogen receptor positive (96.1 v 93.1, p=0.022) although other receptor expressions did not differ. Finally, luminal A tumours were more common in statin users, at the expense of luminal B and HER2-enriched cancers (81.4 v 74.0, p=0.018) (Table 1). Overall breast cancer events were more common in statin non-users compared to users (16.7 v 9.3%, HR 1.80, p&amp;lt;0.0001). Due to the influence of the larger hormone receptor positive cohort, the majority of patients had luminal tumours. Looking to the influence of statins on events within sub-types, users compared to non-users experienced substantially less breast cancer events in luminal B cancers (8.8% v 22.3%, p=0.012 ) and modestly reduced events in luminal A cancers (8.3 v 12.6%, p=0.0326). Considering HER2 positive luminal B cancers relative to those afforded luminal B status by virtue of being high grade, the former group showed significantly less events in statin users v non-users (0 v 19.9%, p=0.0047) whereas no significant protection was observed in the latter (18.2 v 24.6%, p=0.294). Low numbers of HER2 positive hormone receptor negative cases precluded analyzing whether protection extended to all HER2 positive tumours, although none of these patients relapsed. No significant differential effect was found by statin type. In conclusion, statin usage after early breast cancer afforded substantial protection to HER2 positive hormone receptor positive patients, an effect that may extend to all HER2 positive cases. Further validation is warranted. Such patients could be considered for trials exploring statins as agents protecting against relapse. Table 1: Breast tumour demographics comparing statin users to non-users.Statin UseCasesCasesMedian sizeLN positiveLN positiveInvasive GradeInvasive gradeInvasive GradeER +iveER +ivePR -ivePR -iveHER2 +iveHER2 +iveSub-typeSub-typeSub-typen%mmn%n%n%n%n%n%lum A1117(74.0)Grade 144827.6Lum B336(22.3)NO1729(79.0)18607/1787(34.0)Grade 286753.51601/1719(93.1)1348/1565(86.1)144/1498(9.6)HER2 enrich7(0.5)Grade 330718.9TNBC50(3.3).lum A337(81.4)Grade 113130.2lum B68(16.4)YES454(21.0)17151/475(31.8)Grade 224757.0440/458(96.1)363/428(84.8)32/421(7.6)HER2 enrich1(0.2)Grade 35512.7TNBC8(1.9).p (Fishers)NS0.3820.0250.0220.4820.2510.018 Citation Format: Andrew David Redfern, Lisa J Spalding, Robin L Anderson, Hilary Martin. Statin use significantly improves outcome in luminal B relative to luminal A breast cancers [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-12.

Influence of the statin therapy on cardiovascular remodeling in arterial hypertension, combined with subclinical hypothyroidism

There is a proven relation between hypothyroidism and appearance of the pronounced structural and functional changes of the heart and blood vessels as well as atherosclerosis and its related diseases progress. At the same time, there is a lack of information regarding the influence of statins on indices of the structure and function of the heart and blood vessels in patients with arterial hypertension (AH) combined with subclinical hypothyroidism (SH).Aim. To study the effect of the long-term statin therapy on the cardiac structure and function, as well as on vascular remodeling in patients with arterial hypertension combined with subclinical hypothyroidism.Material and methods. The study involved 31 patients with arterial hypertension grade 1–3, stage II, of high and very high additional cardiovascular risk, with a concomitant SH. All patients received a combination of two or three first-line antihypertensive drugs at average therapeutic daily doses and atorvastatin at a dose of 20–30 mg per day.Prior to treatment and after one year of follow-up, all patients underwent an echocardiographic examination and a carotid artery scan on My Lab Seven (Italy) device as well as a 24h-blood pressure monitoring on a bifunctional device “Cardiotechnics-04” (Inkart, St. Petersburg, RF) with the simultaneous registration of BP and ECG.Results. Under the influence of therapy, the target level of systolic blood pressure was reached in 74 % (23/31) of patients during the daytime observation period, in 65 % (20/31) of patients during the nighttime observation period; target diastolic blood pressure for the daytime observation period – in 87 % (27/31) of patients, for the nighttime observation period – in 71 % (22/31) patients. However, there was no significant change in the size of cavities of the left atrium and both ventricles, ejection fraction (before treatment 68.84 ± 5.43 %, after 67.13 ± 5.45 %), thickness of the interventricular septum and posterior wall, relative wall thickness (before treatment 0.41 ± 0.07, after 0.41 ± 0.07, P = 0.871), LV mass index (before treatment 122.29 ± 37.36 g/m2, after 118.00 ± 31.00 g/m2, P = 0.849), indices of diastolic function of the left ventricle (LV). The specific gravity of patients with eccentric LV hypertrophy after a year of treatment increased from 32 % to 39 % (P = 0.5668), with concentric hypertrophy decreased from 42 % to 39 % (P = 0.8107), with normal LV geometry – from 19 % to 16 % (P = 0.7570). The number of patients with AH with a concomitant SH with signs of a concentric LV remodeling remained unchanged – before treatment 6 %, after 6 %. The influence of the statin therapy on vascular remodeling in patients with AH with a concomitant SH was characterized by a tendency towards a decrease in the thickness of the intima-media complex of the right (0.769 ± 0.276 mm vs. 0.701 ± 0.222 mm, P = 0.512) and left (0.759 ± 0.185 mm vs. 0.745 ± 0.179 mm, P = 0.988) common carotid arteries.Conclusion. In patients with AH with a concomitant SH, the antihypertensive therapy during the year with the first-line drugs with addition of statins was associated with achievement of the target SBP level in the active period in 74 %, in the passive period – in 65 % of patients (according to the 24h-BPM data), but was not accompanied by a significant decrease in the cavity size, wall thicknesses, LV mass, improvement of LV diastolic filling, reduction in thickness of the intima-media complex.

Statins and diabetes: focus on pitavastatin

In this review, the focus is to investigate the effects of long-term statin therapy on glucose metabolism. The author analyzed the evidences of randomized clinical trials, meta-analyses, and experimental studies indicating the diabetogenic effect of the most of statins. Possible mechanisms of influence of statins on carbohydrate metabolism are presented. Particular attention is paid to the place of pitavastatin, due to its low diabetogenicity and minimal risk of drug interactions, as well as the need of taking into consideration the risk factors of diabetes and the preventive measures in patients receiving statin therapy.

COMPARISON OF PLASMA COAGULABILITY AFTER SHORT-TERM TREATMENT WITH ROSUVASTATIN VERSUS ATORVASTATIN IN UNSTABLE ANGINA PATIENTS

Statins are the integral medications for the management of patients with acute coronary syndrome including unstable angina (UA) with multiple pleiotropic effects. However, the influence of statins on the coagulation system is controversial. Our study aimed to explore the effects of atorvastatin and rosuvastatin in high doses on some coagulation parameters (prothrombin pool (PP) and soluble fibrin-monomer complexes (SFMC) concentration) after a 7-days follow-up period in patients with UA. We recruited 50 patients aged 55 to 70 years with progressive UA. Standard therapy according to ESC guidelines 2020 was recommended for all patients. Before treatment onset, they were divided into 2 groups: group A – 26 patients were prescribed atorvastatin, group R – 24 patients with rosuvastatin treatment. The blood samples to analyze the concentration of PP and SFMC were collected twice – before the treatment onset and 7 days after. We revealed significant decrease in PP concentration (p=0,02) and increase in SFMC concentration (p=0,01) in group A patients while there were no significant changes of investigated parameters (p=0,94, p=0,57 respectively) in group R. Additionally, we have noted significant negative correlation between baseline PP concentration and direction of PP changes (r=-0,803, p&lt;0,001) as well as PP changes direction and SFMC concentration after treatment (r=-0,655, p&lt;0,001). Thus, we may consider that atorvastatin and rosuvastatin are characterized by different influences on coagulation in patients with progressive UA with standard basic treatment. The rebound coagulation system activation after anticoagulant discontinuation is more pronounced in UA patients against a background of atorvastatin treatment in comparison with rosuvastatin.

Influence of preoperative statins and aspirin administration on biological and magnetic resonance imaging properties in patients with abdominal aortic aneurysm.

Background: Main objective of this study was to evaluate the influence of statins and/or acetylsalicylic acid on biochemical characteristics of abdominal aortic aneurysm (AAA) wall and intraluminal thrombus (ILT). Patients and methods: Fifty patients with asymptomatic infrarenal AAA were analyzed using magnetic resonance imaging on T1w sequence. Relative ILT signal intensity (SI) was determined as a ratio between ILT and psoas muscle SI. Samples containing the full ILT thickness and aneurysm wall were harvested from the anterior surface at the level of the maximal diameter. The concentration of enzymes such as matrix metalloproteinase (MMP) 9, MMP2 and neutrophil elastase (NE/ELA) were analyzed in ILT and AAA wall; while collagen type III, elastin and proteoglycan 4 were analyzed in harvested AAA wall. Oxidative stress in the AAA wall was assessed by catalase and malondialdehyde activity in tissue samples. Results: Relative ILT signal intensity (1.09±0.41 vs 0.89±0.21, p=0.013) were higher in non-statin than in statin group. Patients who were taking aspirin had lower relative ILT area (0.89±0.19 vs 1.13.±0.44, p=0.016), and lower relative ILT signal intensity (0.85 [0.73-1.07] vs 1.01 [0.84-1.19], p=0.021) compared to non-aspirin group. There were higher concentrations of elastin in AAA wall among patients taking both of aspirin and statins (1.21 [0.77-3.02] vs 0.78 (0.49-1.05) ng/ml, p=0.044) than in patients who did not take both of these drugs. Conclusions: Relative ILT SI was lower in patients taking statin and aspirin. Combination of antiplatelet therapy and statins was associated with higher elastin concentrations in AAA wall.

The influence of statins on the risk of post-stroke epilepsy.

Currently, statins are widely used for secondary prevention of stroke due to their pleiotropic neuroprotective effects. Epilepsy is a common complication of cerebrovascular diseases. The purpose of this study was to evaluate the effect of statin therapy on the occurrence of post-stroke epilepsy (PSE). In this prospective cohort study, patients who suffered an ischemic stroke and without history of epilepsy before stroke were enrolled. At baseline, patients were classified according to the particularities of statin therapy. Statin use onset and adherence to treatment were registered as well. After a follow-up period of 1year, we assessed the occurrence of seizures and PSE. Among the 477 patients included in our cohort, there were 91 (19.1%) patients without statins, 160 (33.5%) with simvastatin 20mg, 180 (37.7%) with simvastatin 40mg, and 46 (9.6%) with high-potency statins. Overall, PSE emerged in 53 (11.1%) patients. PSE was significantly more prevalent among those who did not receive statins and those with lower doses of simvastatin. Acute onset of statin use was associated with reduced odds of having PSE. Adequate treatment with statins after stroke may lower the risk of PSE.

The Influence of Statins on the Aerobic Metabolism of Endothelial Cells

Endothelial mitochondrial dysfunction is considered to be the main cause of cardiovascular disease. The aim of this research was to elucidate the effects of cholesterol-lowering statins on the aerobic metabolism of endothelial cells at the cellular and mitochondrial levels. In human umbilical vein endothelial cells (EA.hy926), six days of exposure to 100 nM atorvastatin (ATOR) induced a general decrease in mitochondrial respiration. No changes in mitochondrial biogenesis, cell viability, or ATP levels were observed, whereas a decrease in Coenzyme Q10 (Q10) content was accompanied by an increase in intracellular reactive oxygen species (ROS) production, although mitochondrial ROS production remained unchanged. The changes caused by 100 nM pravastatin were smaller than those caused by ATOR. The ATOR-induced changes at the respiratory chain level promoted increased mitochondrial ROS production. In addition to the reduced level of mitochondrial Q10, the activity of Complex III was decreased, and the amount of Complex III in a supercomplex with Complex IV was diminished. These changes may cause the observed decrease in mitochondrial membrane potential and an increase in Q10 reduction level as a consequence, leading to elevated mitochondrial ROS formation. The above observations highlight the role of endothelial mitochondria in response to potential metabolic adaptations related to the chronic exposure of endothelial cells to statins.

Molecular mechanisms of the cardiotoxic action of anthracycline antibiotics and statin-induced cytoprotective reactions of cardiomyocytes

The manifestation of the side cardiotoxic effect of anthracycline antibiotics limits their use in the treatment of malignant processes in some patients. The review analyzes the main causes of the susceptibility of cardiomyocytes to the damaging effect of anthracyclines, primarily associated with an increase in the processes of free radical oxidation. Currently, research is widely carried out to find ways to reduce anthracycline cardiotoxicity, in particular, the use of cardioprotective agents in the complex treatment of tumors. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) have been shown to improve the function and metabolism of the cardiovascular system under various pathological impacts, therefore, it is proposed to use them to reduce cardiotoxic complications of chemotherapy. Statins exhibit direct (hypolipidemic) and pleiotropic effects due to the blockade of mevalonic acid synthesis and downward biochemical cascades that determine their cardioprotective properties. The main point of intersection of the pharmacological activity of anthracyclines and statins is the ability of both to regulate the functioning of small GTPase from the Rho family, and their effect in this regard is the opposite. The influence of statins on the modification and membrane dislocation of Rho proteins mediates the indirect antioxidant, anti-inflammatory, endothelioprotective, antiapoptotic effect. The mechanism of statin inhibition of doxorubicin blockade of the DNA-topoisomerase complex, which may be important in preventing cardiotoxic damage during chemotherapy, is discussed. At the same time, it should be noted that the use of statins can be accompanied by adverse side effects: a provocation of increased insulin resistance and glucose tolerance, which often causes them to be canceled in patients with impaired carbohydrate metabolism, so further studies are needed here. The review also analyzes data on the antitumor effect of statins, their ability to sensitize the tumor to treatment with cytostatic drug. It has been shown that the relationship between anthracycline antibiotics and statins is characterized not only by antagonism, but also in some cases by synergism. Despite some adverse effects, statins are one of the most promising cardio- and vasoprotectors for use in anthracycline cardiomyopathy.