PURPOSE OF REVIEW: Chronic inflammation has been recognized as one of the most important pathophysiological mechanisms' initiation and progression of atherosclerosis. Statins belong to most successful therapeutic agents in the prevention and treatment of atherothrombotic vascular disease. Their non-lipid related effects including suppression of inflammation have been repeatedly proven in both experimental and clinical settings. RECENT FINDINGS: Recently, the importance of inflammation in the process of atherosclerosis has been confirmed by interventions targeting inflammation selectively. Clinical trial with selective inhibitor of a principal inflammatory mediator interleukin 1-beta - canakinumab - confirmed the notion of direct vasculoprotective effects of primarily targeting inflammation. This has increased interest in the non-lipid, pleiotropic and, particularly, anti-inflammatory effects of statins. Anti-inflammatory effects of statins have been proven both experimentally and in clinical settings beyond any doubt. They comprise a direct positive effect on not only many cell types and pathways that are lipid independent but, also, some that are mediated by lipid modification. Undoubtedly, suppression of inflammatory response by statins contributes to their generally positive action in atherosclerosis and represents an important part of the vasculo- and atheroprotective effect of this drug class.

• Klíčová slova
• Atherosclerosis, Biomarkers, Cardiovascular, Endothelial function, Inflammation, Pleiotropy, Statins,
• MeSH
• ateroskleróza * farmakoterapie   prevence a kontrola   MeSH
• lidé MeSH
• statiny * terapeutické užití   MeSH
• zánět farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• statiny * MeSH

Statins are widely accepted hypolipidemics that work by inhibiting hydroxymethylglutaryl coenzyme A reductase and thereby inhibiting cholesterol synthesis. They significantly reduce cardiovascular risk. Their use could be associated with side effects, which are serious only in rare cases. However, an unhealthy lifestyle, obesity, and elevation of blood lipids do not only damage the cardiovascular system. The current topic not only in hepatology is non-alcoholic fatty liver disease - NAFLD. The aim of this article is, among others, to draw attention to the pleiotropic effects of statins, which could be used in the treatment of this disease in the future. Recent studies have suggested that the administration of statins to patients with NAFLD is beneficial.

• Klíčová slova
• NAFLD, dyslipidemie, hepatopathy, statins,
• MeSH
• kardiovaskulární nemoci * komplikace   prevence a kontrola   MeSH
• lidé MeSH
• nealkoholová steatóza jater * komplikace   farmakoterapie   MeSH
• statiny * škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• statiny * MeSH

The impact of statin therapy on dementia has been a hot topic of debate over the last decade and still remains highly controversial. Among all causes of dementia, vascular dementia (VaD) is the one type that is more likely to benefit from statins. To date no randomized clinical trials have been published and no systematic review has investigated a possible preventive effect of statins on the VaD subtype. In the present literature review, we tried to identify all available data on the effect of statins specifically in patients with VaD, and to further discuss this possible association. Our literature search highlighted two cross-sectional studies, two prospective cohort studies, and one retrospective cohort study. Two of the studies found a significant positive effect of statin treatment on VaD, depicted by the lower incidence of VaD in statin users, while the others reported non-significant associations. The relatively small numbers of VaD patients and statin users, as well as the presence of confounders and biases, make the interpretation of results extremely difficult. Statins may exert a benefit in the prevention of all-type dementia and VaD, through several mechanisms except for hyperlipidemia reduction. A well-designed randomized clinical trial is the ideal study design to address the effect of statin therapy in VaD and to draw final conclusions.

• Klíčová slova
• Cholesterol, HMG-CoA inhibitors, lipid lowering agents, statins, vascular dementia,
• MeSH
• anticholesteremika terapeutické užití   MeSH
• databáze bibliografické statistika a číselné údaje   MeSH
• lidé MeSH
• statiny terapeutické užití   MeSH
• vaskulární demence farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• anticholesteremika MeSH
• statiny MeSH

Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are currently the most effective lipid-lowering drugs, effectively reducing the plasma total cholesterol and low-density lipoprotein, while also decreasing three triacylglycerols and increasing plasma high-density lipoprotein to a certain extent. However, the excessive or long-term use of statins can cause in vitro cytotoxicity, in vivo liver injury, liver necrosis, kidney damage, and myopathy in both human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with statins, and various antioxidants have been evaluated to investigate their protective roles against statin-induced liver, kidney, and muscle toxicities. Widespread attention has been given to statin-induced oxidative stress, with and without the use of other drugs. Much of the information about the mechanism for this reduction comes from cell culture and in experimental animal studies. The primary focus of this article is to summarize the research progress associated with oxidative stress as a plausible mechanism for statin-induced toxicity, as well as its metabolic interactions. This review summarizes the research conducted over the past five years into the production of reactive oxygen species, oxidative stress as a result of statin treatments, and their correlation with statin-induced toxicity and metabolism. Statin-induced metabolism involves various CYP450 enzymes, which provide potential sites for statin-induced oxidative stress, and these metabolic factors are also reviewed. The therapeutics of a variety of compounds against statin-induced organ damage based on their anti-oxidative effects is also discussed to further understand the role of oxidative stress in statin-induced toxicity. This review sheds new light on the critical roles of oxidative stress in statin-induced toxicity and prevention of this oxidative damage, as well as on the contradictions and unknowns that still exist regarding statin toxicity and the cellular effects in terms of organ injury and cell signaling pathways.

• Klíčová slova
• Metabolic interaction, Oxidative stress, Statins, Toxicology,
• MeSH
• lékové interakce MeSH
• lidé MeSH
• oxidační stres účinky léků   MeSH
• předávkování léky MeSH
• statiny škodlivé účinky   farmakokinetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• statiny MeSH

Statin use is associated with increased calorie intake and consequent weight gain. It is speculated that statin-dependent improvements in lipid profile may undermine the perceived need to follow lipid-lowering and other dietary recommendations leading consequently to increased calorie intake. However, increases in calorie intake in statin users may also be related to statin-dependent decreases in satiety factors such as leptin, an adipocyte-derived adipokine. The objective of our study was to examine the direct effects of statins on leptin expression. Adipocytes are the main source of circulating leptin. Therefore, we examined the effects of atorvastatin and simvastatin on leptin expression in cultured human white adipocytes. We show that treatment of white adipocytes with simvastatin and atorvastatin decreases leptin mRNA expression (simvastatin: P = 0.008, atorvastatin: P = 0.03) and leptin secretion (simvastatin: P = 0.0001, atorvastatin: P = 0.0001). Both simvastatin and atorvastatin mediate decreases in leptin expression via extracellular-signal-regulated kinases 1/2 and peroxisome proliferator-activated receptor gamma pathways (simvastatin: P = 0.01, atorvastatin: P = 0.026). Additionally, statin treatment also induced expected increases in adiponectin, while decreasing monocyte chemoattractant protein 1 (MCP1) mRNA. Furthermore, statins increased secretion of both total as well as high molecular weight adiponectin while decreasing MCP1 secretion. To conclude, statins act directly on human white adipocytes to regulate adipokine secretion and decrease leptin expression. Leptin is an important satiety factor. Hence, statin-dependent decreases in leptin may contribute, at least in part, to increases in food intake in statin users.

• Klíčová slova
• Leptin, satiety, statins,
• MeSH
• adiponektin biosyntéza   MeSH
• atorvastatin škodlivé účinky   MeSH
• bílé tukové buňky účinky léků   metabolismus   MeSH
• kultivované buňky MeSH
• leptin biosyntéza   MeSH
• lidé MeSH
• simvastatin škodlivé účinky   MeSH
• statiny škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• adiponektin MeSH
• ADIPOQ protein, human MeSH Prohlížeč
• atorvastatin MeSH
• LEP protein, human MeSH Prohlížeč
• leptin MeSH
• simvastatin MeSH
• statiny MeSH

OBJECTIVE: Statins are widely used drugs for cholesterol lowering, which were recently found to counteract the effects of aberrant fibroblast growth factor receptor (FGFR3) signaling in cell and animal models of FGFR3-related chondrodysplasia. This opened an intriguing therapeutic possibility for human dwarfing conditions caused by gain-of-function mutations in FGFR3, although the mechanism of statin action on FGFR3 remains unclear. Here, we determine the effect of statins on FGFR signaling in chondrocytes. DESIGN: Cultured chondrocyte cell lines, mouse embryonic tibia cultures and limb bud micromasses were treated with FGF2 to activate FGFR signaling. The effects of atorvastatin, fluvastatin, lovastatin and pravastatin on FGFR3 protein stability and on FGFR-mediated chondrocyte growth-arrest, loss of extracellular matrix (ECM), induction of premature senescence and hypertrophic differentiation were evaluated. RESULTS: Statins did not alter the level of FGFR3 protein expression nor produce any effect on FGFR-mediated inhibition of chondrocyte proliferation and hypertrophic differentiation in cultured chondrocyte cell lines, mouse tibia cultures or limb bud micromasses. CONCLUSION: We conclude that statins do not inhibit the FGFR signaling in chondrocytes. Therefore the statin-mediated rescue of FGFR3-related chondrodysplasia, described before, is likely not intrinsic to the growth plate cartilage.

• Klíčová slova
• Achondroplasia, Chondrocytes, FGF signaling, Statins,
• MeSH
• buněčná diferenciace účinky léků   MeSH
• buněčné linie MeSH
• chondrocyty účinky léků   metabolismus   MeSH
• chondrogeneze účinky léků   MeSH
• končetinové pupeny účinky léků   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• lidé MeSH
• myši MeSH
• receptor fibroblastových růstových faktorů, typ 3 antagonisté a inhibitory   metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• statiny farmakologie   MeSH
• techniky tkáňových kultur MeSH
• tibie účinky léků   embryologie   růst a vývoj   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• receptor fibroblastových růstových faktorů, typ 3 MeSH
• statiny MeSH

Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors are commonly used drugs in the treatment of dyslipidemias, primarily raised cholesterol. Recently, many epidemiological and preclinical studies pointed to anti-tumor properties of statins, including anti-proliferative activities, apoptosis, decreased angiogenesis and metastasis. These processes play an important role in carcinogenesis and, therefore, the role of statins in cancer disease is being seriously discussed among oncologists. Anti-neoplastic properties of statins combined with an acceptable toxicity profile in the majority of individuals support their further development as anti-tumor drugs. The mechanism of action, current preclinical studies and clinical efficacy of statins are reviewed in this paper. Moreover, promising results have been reported regarding the statins' efficacy in some cancer types, especially in esophageal and colorectal cancers, and hepatocellular carcinoma. Statins' hepatotoxicity has traditionally represented an obstacle to the prescription of this class of drugs and this issue is also discussed in this review.

• Klíčová slova
• Anti-tumor properties, Cancer risk reduction, Cancer therapy, Carcinogenesis, Chemoprevention, Statins,
• MeSH
• antitumorózní látky škodlivé účinky   terapeutické užití   MeSH
• biomedicínský výzkum MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• nádory farmakoterapie   etiologie   mortalita   MeSH
• preklinické hodnocení léčiv MeSH
• riziko MeSH
• statiny škodlivé účinky   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antitumorózní látky MeSH
• statiny MeSH

Pre-clinical studies from the recent past have indicated that senescent cells can negatively affect health and contribute to premature aging. Targeted eradication of these cells has been shown to improve the health of aged experimental animals, leading to a clinical interest in finding compounds that selectively eliminate senescent cells while sparing non-senescent ones. In our study, we identified a senolytic capacity of statins, which are lipid-lowering drugs prescribed to patients at high risk of cardiovascular events. Using two different models of senescence in human vascular endothelial cells (HUVECs), we found that statins preferentially eliminated senescent cells, while leaving non-senescent cells unharmed. We observed that the senolytic effect of statins could be negated with the co-administration of mevalonic acid and that statins induced cell detachment leading to anoikis-like apoptosis, as evidenced by real-time visualization of caspase-3/7 activation. Our findings suggest that statins possess a senolytic property, possibly also contributing to their described beneficial cardiovascular effects. Further studies are needed to explore the potential of short-term, high-dose statin treatment as a candidate senolytic therapy.

• Klíčová slova
• anoikis, apoptosis, endothelial cells, senescence, senolytics, statins,
• MeSH
• anoikis MeSH
• endoteliální buňky MeSH
• léky proti stárnutí MeSH
• lidé MeSH
• senioři MeSH
• stárnutí buněk * MeSH
• statiny * farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• léky proti stárnutí MeSH
• statiny * MeSH

BACKGROUND: Growing evidence suggests that different statins are able to lower brain cholesterol synthesis. It is not clear yet whether lipophilic statins influence brain cholesterol in different way than hydrophilic ones. SOURCES OF MATERIAL: The MEDLINE database. FINDINGS: According to the data reported thus far, statins may influence brain cholesterol metabolism directly (because they are able to penetrate BBB no matter whether they are hydrophilic or lipophilic) and also indirectly (by lowering plasma cholesterol). Although the definite mechanism is not known yet, it becomes obvious that statins do not only influence peripheral but also central cholesterol pool. CONCLUSION: Better understanding of the effects of statins on brain metabolism becomes more important because many studies bring evidence of a possible link between cholesterol and neurodegeneration.

• MeSH
• Alzheimerova nemoc metabolismus   MeSH
• cholesterol metabolismus   MeSH
• databáze faktografické MeSH
• hematoencefalická bariéra metabolismus   MeSH
• lidé MeSH
• mozek účinky léků   metabolismus   MeSH
• statiny farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cholesterol MeSH
• statiny MeSH

Statins, the drugs used for the treatment of hypercholesterolemia, have come into the spotlight not only as chemoadjuvants, but also as potential stem cell modulators in the context of regenerative therapy. In our study, we compared the in vitro effects of all clinically used statins on the viability of human pancreatic cancer (MiaPaCa-2) cells, non-cancerous human embryonic kidney (HEK 293) cells and adipose-derived mesenchymal stem cells (ADMSC). Additionally, the effect of statins on viability of MiaPaCa-2 and ADMSC cells spheroids was tested. Furthermore, we performed a microarray analysis on ADMSCs treated with individual statins (12 μM) and compared the importance of the effects of statins on gene expression between stem cells and pancreatic cancer cells. Concentrations of statins that significantly affected cancer cells viability (< 40 μM) did not affect stem cells viability after 24 h. Moreover, statins that didn´t affect viability of cancer cells grown in a monolayer, induce the disintegration of cancer cell spheroids. The effect of statins on gene expression was significantly less pronounced in stem cells compared to pancreatic cancer cells. In conclusion, the low efficacy of statins on non-tumor and stem cells at concentrations sufficient for cancer cells growth inhibition, support their applicability in chemoadjuvant tumor therapy.

• Klíčová slova
• 3-Hydroxy-3-methylglutaryl coenzyme A inhibitors, Cell spheroids, Microarray analysis, Pancreatic cancer cells, Statins, Stem cells,
• MeSH
• buněčné sféroidy účinky léků   MeSH
• HEK293 buňky MeSH
• lidé MeSH
• mezenchymální kmenové buňky * účinky léků   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory slinivky břišní * farmakoterapie   patologie   metabolismus   MeSH
• statiny * farmakologie   MeSH
• viabilita buněk * účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• statiny * MeSH