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BMC Complementary Medicine and Therapies Nov 2023Cardiovascular disease and cancer are the main causes of morbidity and mortality worldwide. Studies have shown that these two diseases may have some common risk factors....
BACKGROUND
Cardiovascular disease and cancer are the main causes of morbidity and mortality worldwide. Studies have shown that these two diseases may have some common risk factors. Atorvastatin is mainly used for the treatment of atherosclerosis in clinic. A large number of studies show that atorvastatin may produce anti-tumor activities. This study aimed to predict the common targets of atorvastatin against atherosclerosis and non-small cell lung cancer (NSCLC) based on network pharmacology.
METHODS
The target genes of atherosclerosis and NSCLC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The disease-target-component model map and the core network were obtained using Cytoscape 3.7.1. The MTS and wound healing assay were used to detect the effect of atorvastatin on cell viability and migration of A549 cells. The expression of potential common target genes of atorvastatin against atherosclerosis and NSCLC were confirmed in A549 cells and lung cancer tissues of patients.
RESULTS
We identified 15 identical pathogenic genes, and four of which (MMP9, MMP12, CD36, and FABP4) were considered as the key target genes of atorvastatin in anti-atherosclerosis and NSCLC. The MTS and wound healing assays revealed that atorvastatin decreased A549 cells migration significantly. Atorvastatin markedly decreased the expression of MMP9, MMP12, CD36, and FABP4 in A549 cells and patients were treated with atorvastatin.
CONCLUSIONS
This study demonstrated 15 common pathogenic genes in both atherosclerosis and NSCLC. And verified that MMP 9, MMP 12, CD 36 and FABP 4 might be the common target genes of atorvastatin in anti-atherosclerosis and NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Matrix Metalloproteinase 9; Atorvastatin; Matrix Metalloproteinase 12
PubMed: 37978381
DOI: 10.1186/s12906-023-04255-7 -
Journal of Lipid Research Mar 2020Atherosclerosis-related CVD causes nearly 20 million deaths annually. Most patients are treated after plaques develop, so therapies must regress existing lesions....
Atherosclerosis-related CVD causes nearly 20 million deaths annually. Most patients are treated after plaques develop, so therapies must regress existing lesions. Current therapies reduce plaque volume, but targeting all apoB-containing lipoproteins with intensive combinations that include alirocumab or evinacumab, monoclonal antibodies against cholesterol-regulating proprotein convertase subtilisin/kexin type 9 and angiopoietin-like protein 3, may provide more benefit. We investigated the effect of such lipid-lowering interventions on atherosclerosis in APOE*3-Leiden.CETP mice, a well-established model for hyperlipidemia. Mice were fed a Western-type diet for 13 weeks and thereafter matched into a baseline group (euthanized at 13 weeks) and five groups that received diet alone (control) or with treatment [atorvastatin; atorvastatin and alirocumab; atorvastatin and evinacumab; or atorvastatin, alirocumab, and evinacumab (triple therapy)] for 25 weeks. We measured effects on cholesterol levels, plaque composition and morphology, monocyte adherence, and macrophage proliferation. All interventions reduced plasma total cholesterol (37% with atorvastatin to 80% with triple treatment; all < 0.001). Triple treatment decreased non-HDL-C to 1.0 mmol/l (91% difference from control; < 0.001). Atorvastatin reduced atherosclerosis progression by 28% versus control ( < 0.001); double treatment completely blocked progression and diminished lesion severity. Triple treatment regressed lesion size versus baseline in the thoracic aorta by 50% and the aortic root by 36% (both < 0.05 vs. baseline), decreased macrophage accumulation through reduced proliferation, and abated lesion severity. Thus, high-intensive cholesterol-lowering triple treatment targeting all apoB-containing lipoproteins regresses atherosclerotic lesion area and improves lesion composition in mice, making it a promising potential approach for treating atherosclerosis.
Topics: Administration, Oral; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Atorvastatin; Drug Therapy, Combination; Female; Mice; Mice, Inbred C57BL; Mice, Transgenic; Plaque, Atherosclerotic
PubMed: 31843957
DOI: 10.1194/jlr.RA119000419 -
Epilepsy & Behavior : E&B Jan 2018Temporal lobe epilepsy (TLE) is the most frequent and medically refractory type of epilepsy in humans. In addition to seizures, patients with TLE suffer from behavioral...
Temporal lobe epilepsy (TLE) is the most frequent and medically refractory type of epilepsy in humans. In addition to seizures, patients with TLE suffer from behavioral alterations and cognitive deficits. Poststatus epilepticus model of TLE induced by pilocarpine in rodents has enhanced the understanding of the processes leading to epilepsy and thus, of potential targets for antiepileptogenic therapies. Clinical and experimental evidence suggests that inflammatory processes in the brain may critically contribute to epileptogenesis. Statins are inhibitors of cholesterol synthesis, and present pleiotropic effects that include antiinflammatory properties. We aimed the present study to test the hypothesis that atorvastatin prevents behavioral alterations and proinflammatory state in the early period after pilocarpine-induced status epilepticus. Male and female C57BL/6 mice were subjected to status epilepticus induced by pilocarpine and treated with atorvastatin (10 or 100mg/kg) for 14days. Atorvastatin slightly improved the performance of mice in the open-field and object recognition tests. In addition, atorvastatin dose-dependently decreased basal and status epilepticus-induced levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (INF-γ) and increased interleukin-10 (IL-10) levels in the hippocampus and cerebral cortex. The antiinflammatory effects of atorvastatin were qualitatively identical in both sexes. Altogether, these findings extend the range of beneficial actions of atorvastatin and indicate that its antiinflammatory effects may be useful after an epileptogenic insult.
Topics: Animals; Anti-Inflammatory Agents; Atorvastatin; Cerebral Cortex; Cognition Disorders; Convulsants; Disease Models, Animal; Epilepsy; Female; Gene Expression Regulation; Hippocampus; Humans; Interleukin-1beta; Interleukin-6; Male; Mice; Mice, Inbred C57BL; Pilocarpine; Seizures; Status Epilepticus
PubMed: 29186698
DOI: 10.1016/j.yebeh.2017.10.021 -
Oxidative Medicine and Cellular... 2022Abdominal or pelvic radiotherapy (RT) often results in small intestinal injury, such as apoptosis of epithelial cells and shortening of the villi. Atorvastatin, a...
Abdominal or pelvic radiotherapy (RT) often results in small intestinal injury, such as apoptosis of epithelial cells and shortening of the villi. Atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has many biological effects including cholesterol reduction, protection from cell damage, and autophagy activation. To reduce the extent of radiotherapy- (RT-) induced enteritis, we investigated the protective effects of atorvastatin against RT-induced damage of the intestinal tract. In this study, C57BL/6 mice were randomly distributed into the following groups ( = 8 per group): (1) control group: mice were fed water only, (2) atorvastatin group (Ator): mice were administered atorvastatin, (3) irradiation group (IR): mice received abdominal RT, (4) Ator+IR group: mice received abdominal RT following atorvastatin administration, and (5) Ator+IR+3-MA group: abdominal RT following atorvastatin and 3-methyladenine (an autophagy inhibitor) administration. Based on the assessment of modified Chiu's injury score and villus/crypt ratio, we found that atorvastatin administration significantly reduced intestinal mucosal damage induced by RT. Atorvastatin treatment reduced apoptosis (cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase), DNA damage (H2AX and 53BP1), oxidative stress (OS, 4-hydroxynonenal), inflammatory molecules (phospho-NF-B p65 and TGF-), fibrosis (collagen I and collagen III), barrier leakage (claudin-2 and fluorescein isothiocyanate-dextran), disintegrity (fatty acid-binding protein 2), and dysfunction (lipopolysaccharide) caused by RT in small intestinal tissue. In addition, atorvastatin upregulated the expression of autophagy-active molecules (LC3B), antioxidants (heme oxygenase 1 and thioredoxin 1), and tight junction proteins (occludin and zonula occludens 1). However, the biological functions of atorvastatin in decreasing RT-induced enteritis were reversed after the administration of 3-MA; the function of antioxidant molecules and activity of thioredoxin reductase were independent of autophagy activation. Our results indicate that atorvastatin can effectively relieve RT-induced enteritis through autophagy activation and associated biological functions, including maintaining integrity and function and decreasing apoptosis, DNA damage, inflammation, OS, and fibrosis. It also acts via its antioxidative capabilities.
Topics: Animals; Antioxidants; Atorvastatin; Autophagy; Fibrosis; Mice; Mice, Inbred C57BL
PubMed: 36092168
DOI: 10.1155/2022/7957255 -
Biomolecules Jul 2021Genistein (4,5,7-trihydroxyisoflavone) is abundant in various dietary vegetables, especially soybeans, and is known to have not only an estrogenic effect but also an...
Genistein (4,5,7-trihydroxyisoflavone) is abundant in various dietary vegetables, especially soybeans, and is known to have not only an estrogenic effect but also an antiadipogenic effect. Atorvastatin (dihydroxy monocarboxylic acid) is a statin used to prevent heart disease. Although genistein and atorvastatin have been reported to possess antiadipogenic effects, their combined effects are still unclear. The aim of the current study was to explore whether the combination of genistein and atorvastatin at low concentrations significantly suppresses adipogenesis in a murine preadipocyte cell line (3T3-L1) compared to treatment with genistein or atorvastatin alone. Our results showed that cotreatment with 50 µM genistein and 50 nM atorvastatin significantly suppressed preadipocyte differentiation, whereas when each compound was used alone, there was no inhibitory effect. Additionally, cotreatment with genistein and atorvastatin significantly downregulated adipogenic marker proteins, including mitogen-activated protein kinases (MAPKs), peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), glucocorticoid receptor (GR), and CCAAT/enhancer-binding protein β (C/EBPβ). This is the first evidence of the combined antiadipogenic effects of genistein and atorvastatin. Although additional experiments are required, combinational treatment with genistein and atorvastatin may be an alternative treatment for menopause-associated lipid metabolic disorders and obesity.
Topics: 3T3-L1 Cells; Adipogenesis; Animals; Atorvastatin; CCAAT-Enhancer-Binding Proteins; Cell Differentiation; Drug Synergism; Genistein; Mice; Mitogen-Activated Protein Kinases; PPAR gamma; Receptors, Glucocorticoid
PubMed: 34356676
DOI: 10.3390/biom11071052 -
Fundamental & Clinical Pharmacology Feb 2021
Targeting IL-10, ZO-1 gene expression and IL-6/STAT-3 trans-signalling by a combination of atorvastatin and mesalazine to enhance anti-inflammatory effects and attenuate progression of oxazolone-induced colitis.
Topics: Anti-Inflammatory Agents; Atorvastatin; Colitis; Gene Expression; Humans; Interleukin-10; Interleukin-6; Mesalamine; Oxazolone
PubMed: 33289917
DOI: 10.1111/fcp.12638 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2021The aim: In this study, we try to investigate whether evolocumab or its combination with atorvastatin has potent effect on lipid profile?
OBJECTIVE
The aim: In this study, we try to investigate whether evolocumab or its combination with atorvastatin has potent effect on lipid profile?
PATIENTS AND METHODS
Materials and methods: Forty local domestic male rabbits were included in this study, and categorized into four group, two untreated group (nohypercholostermic and untreated hypercholostermic) and treated groups (evolocumab treated group at dose 6.1mg/kg/2Wk and atorvastatin treated group at dose 3.5 mg/kg/day),the blood samples were analyzed at base line and after 5week and at the end of the study after 10 weeks for lipid profile by standard enzymatic methods.
RESULTS
Results: The serum levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C),were increased after 10 weeks of administration of the atherogenic diet significantly (p<0.05) as compared with other groups (group I: 61.19 ± 14, group ΙΙ: 1301 ± 443, group ΙΙΙ 41.01 ± 5.81: 280 ± 50, group ΙV: 190 ± 38 group Ι: 46 ± 15.0, group ΙΙ: 256.0 ± 24.0, group ΙΙΙ: 101.0±28, group ΙV: 48.18 ± 15.27, group Ι: 29±14.50, group ΙΙ: 929±251.0, group ΙΙΙ: 283.0±36, group ΙV: 209.0±33mg/dl) respectively while the levels of high-density lipoprotein cholesterol (HDL-C) decrease (18.0±4.1 to 15.0±3.0mg/dl). Compared with evolocumab monotherapy, combination of evolocumab and atorvastatin reduce serum level of total cholesterol, triglyceride and low density lipoprotein more than that of evolocumab.
CONCLUSION
Conclusions: Preproteins convert as esubtilisin/kexin type 9 inhibitor regulates the serum levels of lipid and cholesterol by lowering LDL-C, and the results also indicate that combination of evolocumab and atorvastatin are more potent in lowering the lipid profile and then reduce progression of atherosclerosis than evolocumab alone in rabbits suggesting that this combination might be beneficial for treatment of atherosclerosis.
Topics: Animals; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Atorvastatin; Cholesterol, LDL; Lipids; Male; Rabbits
PubMed: 35058387
DOI: No ID Found -
Redox Report : Communications in Free... Dec 2022Oxidative damage is critical in the pathogenesis of ovarian ischaemia/reperfusion (I/R) injury, and statins have been reported to exert antioxidant activity. However,...
BACKGROUND
Oxidative damage is critical in the pathogenesis of ovarian ischaemia/reperfusion (I/R) injury, and statins have been reported to exert antioxidant activity. However, the role of VCAM-1 and xanthine oxidase (XO)/uric acid (UA) in ovarian I/R injury is not known. Also, whether or not atorvastatin exerts antioxidant activity like other statins is unclear.
OBJECTIVES
This study investigated the involvement of VCAM-1 and XO/UA in ovarian I/R injury and the likely protective role of atorvastatin.
METHODS
Forty female Wistar rats were randomized into sham-operated, ischaemia, ischaemia/reperfusion (I/R), ischaemia and atorvastatin, and I/R and atorvastatin.
RESULTS
In comparison with the sham-operated group, atorvastatin blunted ischaemia and I/R-induced distortion of ovarian histoarchitecture and follicular degeneration. Also, atorvastatin alleviated ischaemia and I/R-induced rise in XO, UA, and malondialdehyde, which was accompanied by inhibition of ischaemia and I/R-induced reductions in reduced glutathione level, enzymatic antioxidant activities and increase in myeloperoxidase activity and TNF-α and IL-6 levels by atorvastatin treatment. Additionally, atorvastatin blocked ischaemia and I/R-induced increase in VCAM-1 expression, caspase 3 activity, 8-hydroxydeoxyguanosine level and ovarian DNA fragmentation index.
CONCLUSION
For the first time, this study revealed that atorvastatin-mediated downregulation of VCAM-1 and XO/UA/caspase 3 signaling averts oxidative injury, inflammation, and apoptosis induced by ovarian ischaemia/reperfusion injury.
Topics: Animals; Female; Rats; 8-Hydroxy-2'-Deoxyguanosine; Antioxidants; Apoptosis; Atorvastatin; Caspase 3; Down-Regulation; Glutathione; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-6; Ischemia; Malondialdehyde; Oxidative Stress; Peroxidase; Rats, Wistar; Reperfusion Injury; Tumor Necrosis Factor-alpha; Uric Acid; Vascular Cell Adhesion Molecule-1; Xanthine Oxidase
PubMed: 36200598
DOI: 10.1080/13510002.2022.2129192 -
Iranian Journal of Medical Sciences Mar 2022Negative effects of statins on glucose metabolism have been reported. The present study aimed to investigate the effects of co-administration of vitamin E and... (Randomized Controlled Trial)
Randomized Controlled Trial
Co-Administration of Vitamin E and Atorvastatin Improves Insulin Sensitivity and Peroxisome Proliferator-Activated Receptor-γ Expression in Type 2 Diabetic Patients: A Randomized Double-Blind Clinical Trial.
BACKGROUND
Negative effects of statins on glucose metabolism have been reported. The present study aimed to investigate the effects of co-administration of vitamin E and atorvastatin on glycemic control in hyperlipidemic patients with type 2 diabetes mellitus (T2DM).
METHODS
A randomized double-blind clinical trial was conducted at Vali-e-Asr Teaching Hospital (Zanjan, Iran) from July 2017 to March 2018. A total of 30 T2DM female patients were allocated to two groups, namely atorvastatin with placebo (n=15) and atorvastatin with vitamin E (n=15). The patients received daily 20 mg atorvastatin and 400 IU vitamin E or placebo for 12 weeks. Anthropometric and biochemical measures were recorded pre- and post-intervention. Peroxisome proliferator-activated receptor-γ () expression was measured in peripheral blood mononuclear cells (PBMCs). Independent sample test and paired test were used to analyze between- and within-group variables, respectively. The analysis of covariance (ANCOVA) was used to adjust the effect of baseline variables on the outcomes. P<0.05 was considered statistically significant.
RESULTS
After baseline adjustment, there was a significant improvement in homeostatic model assessment for insulin resistance (HOMA-IR) (P=0.04) and serum insulin (P<0.001) in the atorvastatin with vitamin E group compared to the atorvastatin with the placebo group. In addition, co-administration of vitamin E with atorvastatin significantly upregulated PPAR-γ expression (OR=5.4, P=0.04) in the PBMCs of T2DM patients.
CONCLUSION
Co-administration of vitamin E and atorvastatin reduced insulin resistance and improved mRNA expression. Further studies are required to substantiate our findings.
TRIAL REGISTRATION NUMBER
IRCT 20170918036256N.
Topics: Atorvastatin; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Insulin Resistance; Leukocytes, Mononuclear; PPAR gamma; Vitamin E
PubMed: 35291435
DOI: 10.30476/ijms.2021.89102.1981 -
Molecules (Basel, Switzerland) Jan 2023Many studies have shown that alterations in the gut microbiota are associated with hypertension. Our study aimed to observe the characteristics of the gut microbiota in...
Many studies have shown that alterations in the gut microbiota are associated with hypertension. Our study aimed to observe the characteristics of the gut microbiota in hypertension and to further explore whether drug molecules can play a therapeutic role in hypertension by interfering with the gut microbiota. We evaluated the differences in the composition of the gut microbiota in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Meanwhile, three first-line cardiovascular disease (CVD) drugs, losartan, atorvastatin, and aspirin, were used to treat the SHR in order to observe their effects on the gut microbiota in SHR. The 16S rDNA results showed that the diversity and richness of the gut microbiota in SHR were significantly reduced compared with that of the WKY, the Firmicutes/Bacteroidetes ratio was increased, the abundances of and short chain fatty acids (SCFAs)-producing bacteria decreased, and the abundance of lactate-producing bacteria increased. In addition to lowering the blood pressure, losartan increased the abundances of , and in SHR, reduced the abundances of , and , reduced the Firmicutes/Bacteroidetes ratio, and rebalanced the gut microbiota. Losartan also increased the abundances of and SCFAs-producing bacteria and reduced the abundance of lactate-producing bacteria. However, atorvastatin and aspirin had no significant effect on the gut microbiota in SHR. The above results showed that losartan could change the characteristics of the gut microbiota in hypertension and rebalance the gut microbiota, which may be related to lowering the blood pressure. Atorvastatin and aspirin have no significant influence on the gut microbiota in SHR.
Topics: Rats; Animals; Losartan; Blood Pressure; Rats, Inbred SHR; Atorvastatin; Gastrointestinal Microbiome; Aspirin; Hypertension; Rats, Inbred WKY
PubMed: 36677668
DOI: 10.3390/molecules28020612