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European Heart Journal Supplements :... Apr 2024There is a clear demonstration of the inverse linear correlation between LDL cholesterol levels and clinical benefit. However, the timing of the action of lipid-lowering...
There is a clear demonstration of the inverse linear correlation between LDL cholesterol levels and clinical benefit. However, the timing of the action of lipid-lowering drugs is not clear. According to animal studies with recombinant lipoprotein A-1, the composition of atherosclerosis changes within 40 h (with variations in lipid and inflammatory contents). Progression-regression studies of atherosclerosis in humans confirm the data, highlighting a rapid change in the plaque over 5 weeks. The data are also in line with what emerges from the survival curves of the old study comparing atorvastatin 80 mg vs. placebo (Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering). The spacing of the curves occurs after only 4 weeks, indicating the precociousness of the favourable effects of powerful statins. Finally, a recent Odyssey analysis compared the risk of cardiac death and coronary revascularization between a group in which alirocumab lowered LDL cholesterol to below 15 mg (Group 1 and in which the drug was therefore stopped) against the subjects in the placebo group (Group 2), applying a propensity score matching. The primary endpoint occurred in a lower percentage of patients in Group 1 (6.4 vs. 8.4%). Furthermore, patients in Group 1 had a significantly lower hazard ratio (HR) for major adverse cardiovascular events [0.72; 95% confidence interval (CI) 0.51-0.997; = 0.047] compared with the entire alirocumab group vs. placebo (HR 0.85; 95% CI 0.78-0.93; < 0.001). According to these preliminary observations, aggressive and early treatment of hypercholesterolaemia in subjects with acute coronary syndrome translates into improved clinical results compared with a strategy that provides for more gradual control. These data will need to be confirmed through further prospective clinical studies and ideally with early conducted atherosclerosis regression studies.
PubMed: 38867873
DOI: 10.1093/eurheartjsupp/suae010 -
Frontiers in Pharmacology 2024Neuroinflammation pathways have been associated with the development of major depressive disorders (MDD). The anti-inflammatory characteristics of statins have been...
Effect of a high dose atorvastatin as added-on therapy on symptoms and serum AMPK/NLRP3 inflammasome and IL-6/STAT3 axes in patients with major depressive disorder: randomized controlled clinical study.
BACKGROUND
Neuroinflammation pathways have been associated with the development of major depressive disorders (MDD). The anti-inflammatory characteristics of statins have been demonstrated to have significance in the pathophysiology of depression.
AIM
To investigate the mechanistic pathways of high dose atorvastatin in MDD.
PATIENTS AND METHODS
This trial included 60 patients with MDD who met the eligibility requirements. Two groups of patients (n = 30) were recruited by selecting patients from the Psychiatry Department. Group 1 received 20 mg of fluoxetine plus a placebo once daily. Group 2 received fluoxetine and atorvastatin (80 mg) once daily. All patients were assessed by a psychiatrist using the Hamilton Depression Rating Scale (HDRS). A HDRS score of ≤7 indicates remission or partial remission [HDRS<17 and>7]. Response was defined as ≥ 50% drop in the HDRS score. The serum concentrations of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP-3), interleukin-6 (IL-6), adenosine monophosphate activated protein kinase (AMPK), and signal transducer and activator of transcription factor-3 (STAT-3) were measured.
RESULTS
The atorvastatin group showed a significant reduction in the levels of all measured markers along with a statistical increase in the levels of AMPK when compared to the fluoxetine group. The atorvastatin group displayed a significant decrease in HDRS when compared to its baseline and the fluoxetine group. The response rate and partial remission were higher in the atorvastatin group than fluoxetine ( = 0.03, and = 0.005), respectively.
CONCLUSION
These results imply that atorvastatin at high doses may be a promising adjuvant therapy for MDD patients by altering the signaling pathways for AMPK/NLRP3 and IL-6/STAT-3.
CLINICAL TRIAL REGISTRATION
clinicaltrials.gov, identifier NCT05792540.
PubMed: 38855751
DOI: 10.3389/fphar.2024.1381523 -
Cureus May 2024Background and objectives Ginsenoside Re (Re), a protopanaxatriol-type saponin extracted from ginseng, is known to have potential cardioprotective effects; however, the...
Background and objectives Ginsenoside Re (Re), a protopanaxatriol-type saponin extracted from ginseng, is known to have potential cardioprotective effects; however, the mechanisms of Re in improving cardiac hypertrophy have not been fully elucidated. This study aimed to investigate the therapeutic effects and underlying mechanism of Re on isoproterenol (ISO)-induced cardiac hypertrophy and . Methods Rats were intraperitoneally injected with ISO 30 mg/kg thrice daily for 14 consecutive days to induce cardiac hypertrophy, and these rats were treated with atorvastatin (ATC, 20 mg/kg) or Re (20 mg/kg or 40 mg/kg) once daily for three days in advance until the end of the experiment. Heart weight index, hematoxylin and eosin staining, and hypertrophy-related fetal gene expression were measured to evaluate the effect of Re on cardiac hypertrophy . Meanwhile, the rat H9c2 cardiomyocyte hypertrophy model was induced by ISO 10 μM for 24 hours. Cell surface area and hypertrophy-related fetal gene expression were determined to assess the effect of Re on ISO-induced cardiomyocyte hypertrophy . The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in both serum and cardiomyocytes were detected by enzymatic colorimetric assays. Furthermore, we chose cholesteryl ester transfer protein (CETP) as a target to explore the influence of Re on CETP expression and through real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay. Results Intraperitoneal administration of ISO into rats resulted in increases in cross-sectional cardiomyocyte area, the ratio of heart weight to body weight, the ratio of left ventricular weight to body weight, and the ratio of right ventricular weight to body weight, as well as reactivation of fetal genes; however, treatment with Re or ATC ameliorated most of these hypertrophic responses. Similarly, Re pronouncedly alleviated ISO-induced cardiomyocyte hypertrophy, as evidenced by a decreased cell surface area and downregulation of fetal genes. Moreover, our and data revealed that Re reduced TC, TG, and LDL-C levels, and enhanced HDL-C levels. Re improved cardiac hypertrophy mainly associated with the inhibition of mRNA level and protein expression of CETP, to an extent comparable to that of the classical CETP inhibitor, anacetrapib. Conclusions Our research found that CETP inhibition contributes to the protection of Re against ISO-induced cardiac hypertrophy, which provides evidence for the application of Re for cardiovascular disease treatments.
PubMed: 38854305
DOI: 10.7759/cureus.59942 -
Life Sciences Aug 2024Atorvastatin is a commonly used cholesterol-lowering drug that possesses non-canonical anti-inflammatory properties. However, the precise mechanism underlying its...
AIMS
Atorvastatin is a commonly used cholesterol-lowering drug that possesses non-canonical anti-inflammatory properties. However, the precise mechanism underlying its anti-inflammatory effects remains unclear.
MATERIALS AND METHODS
The acute phase of ulcerative colitis (UC) was induced using a 5 % dextran sulfate sodium (DSS) solution for 7 consecutive days and administrated with atorvastatin (10 mg/kg) from day 3 to day 7. mRNA-seq, histological pathology, and inflammatory response were determined. Intestinal microbiota alteration, tryptophan, and its metabolites were analyzed through 16S rRNA sequencing and untargeted metabolomics.
KEY FINDINGS
Atorvastatin relieved the DSS-induced UC in mice, as evidenced by colon length, body weight, disease activity index score and pathological staining. Atorvastatin treatment reduced the level of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Atorvastatin also relieved the intestinal microbiota disorder caused by UC and decreased the proliferation of pernicious microbiota such as Akkermansia and Bacteroides. Atorvastatin dramatically altered tryptophan metabolism and increased the fecal contents of tryptophan, indolelactic acid (ILA), and indole-3-acetic acid (IAA). Furthermore, atorvastatin enhanced the expression level of aryl hydrocarbon receptor (AhR) and interleukin-22 (IL-22) and further promoted the expression level of intestinal tight junction proteins, such as ZO-1 and occludin, in colitis mice.
SIGNIFICANCE
These findings indicated that atorvastatin could alleviate UC by regulating intestinal flora disorders, promoting microbial tryptophan metabolism, and repairing the intestinal barrier.
Topics: Animals; Colitis, Ulcerative; Atorvastatin; Gastrointestinal Microbiome; Tryptophan; Mice; Mice, Inbred C57BL; Dextran Sulfate; Male; Anti-Inflammatory Agents; Colon
PubMed: 38852795
DOI: 10.1016/j.lfs.2024.122790 -
Current Health Sciences Journal 2024Atorvastatin is an HMG-CoA reductase inhibitor that is prescribed to prevent adverse cardiovascular events by reducing blood total cholesterol (Chol) and LDL-Chol. Here...
Atorvastatin is an HMG-CoA reductase inhibitor that is prescribed to prevent adverse cardiovascular events by reducing blood total cholesterol (Chol) and LDL-Chol. Here we report a case related to an unusual response of HDL-Chol upon the administration of atorvastatin following an acute myocardial infarction. While atorvastatin substantially reduced LDL and triglycerides (TAG) of the patient as desired, it also lowered the HDL significantly, and in a dose-dependent manner. It is widely known that statins have several major side effects, but a significant suppression on HDL has been rarely reported so far. In addition, atorvastatin is deemed the likely cause for unintentional weight loss of this subject.
PubMed: 38846474
DOI: 10.12865/CHSJ.50.01.19 -
Respiratory Medicine Case Reports 2024There is no approved drug treatment for autoimmune pulmonary alveolar proteinosis (APAP), although traditionally requires complex treatments such as whole lung lavage...
There is no approved drug treatment for autoimmune pulmonary alveolar proteinosis (APAP), although traditionally requires complex treatments such as whole lung lavage (WLL). We herein report on a 67-year-old man diagnosed with APAP. Treatment with atorvastatin (5 mg daily) resulted in significant improvement in symptoms, lung function, and computed tomography findings, with enhanced oxygenation, although serum anti-GM-CSF antibody levels remained elevated. This case suggests that the remission observed in this case could potentially be attributed to a direct effect of atorvastatin within the pulmonary alveoli. Statins may be considered as one of the treatment options for APAP.
PubMed: 38845787
DOI: 10.1016/j.rmcr.2024.102042 -
Archivos de Cardiologia de Mexico Jun 2024To analyse the incidence and risk of recurrent major adverse cardiovascular events (MACE), level of risk factor control, treatment persistence and cost of the CNIC...
OBJECTIVE
To analyse the incidence and risk of recurrent major adverse cardiovascular events (MACE), level of risk factor control, treatment persistence and cost of the CNIC polypill version containing acetylsalicylic acid (ASA) 100 mg, atorvastatin 20 mg (A20), and ramipril 2.5, 5.0 or 10 mg in secondary cardiovascular prevention patients.
METHOD
Subanalysis of the observational, retrospective, multicentre, NEPTUNO study in patients treated for two years with the CNIC polypill A20, the same monocomponents as single drugs, equipotent drugs, and other therapies.
RESULTS
922 patients were included in each group. The risk of recurrent MACE was lower among CNIC A20 polypill users than all others (21%, 23% and 26% increased risk among the monocomponents, equipotent or other therapy cohorts, respectively; p < 0.05). The magnitude of the mean change in low-density lipoprotein cholesterol and blood pressure, as well as the increase in the proportion of patients achieving target goals, was also greater among patients treated with the CNIC A20 polypill than in any of the other cohorts (all p < 0.001). Treatment persistence was significantly higher in patients treated with the CNIC A20 polypill (p < 0.001) and was a less costly strategy than any other therapeutic option.
CONCLUSIONS
In patients in secondary cardiovascular prevention, the CNIC A20 polypill (ASA 100 mg, atorvastatin 20 mg, and ramipril 2.5, 5.0 or 10 mg) constitutes a valid therapeutic option with similar benefits and outcomes to the version of the polypill with atorvastatin 40 mg.
PubMed: 38843861
DOI: 10.24875/ACM.23000230 -
Environmental Research Jun 2024In this study, bimetallic Cu-Fe nanoparticles were synthesized using the green approach with Piper betle leaves, and the removal efficiency of one of the pharmaceutical...
In this study, bimetallic Cu-Fe nanoparticles were synthesized using the green approach with Piper betle leaves, and the removal efficiency of one of the pharmaceutical compounds, Atorvastatin, was investigated. UV, SEM, FTIR, EDAX, particle size, and zeta potential measurements were used to confirm nanoparticle fabrication. The removal efficiency of Atorvastatin (10 mg/L) by bimetallic Cu-Fe nanoparticles was 67% with a contact time of 30 min at pH 4, the adsorbent dosage of 0.2 g/L, and stirring at 100 rpm. Piper betle bimetallic Cu-Fe nanoparticles have demonstrated excellent stability, reusability, and durability, even after being reused five times. Furthermore, the synthesized bimetallic Cu-Fe nanoparticles demonstrated remarkable antimicrobial properties against gram-negative strains such as Escherichia coli and Klebsiella pneumoniae, gram-positive strains such as Staphylococcus aureus and Bacillus subtilis, and fungi such as Aspergillus niger. In addition, the antioxidant properties of the synthesized bimetallic Cu-Fe nanoparticles were assessed using the DPPH radical scavenging assay. The results indicated that the nanoparticles had good antioxidant activity. Thus, using Piper betle extract to make Cu-Fe nanoparticles made the procedure less expensive, chemical-free, and environmentally friendly, and the synthesized bimetallic Cu-Fe nanoparticles helped remove the pharmaceutical compound Atorvastatin from wastewater.
PubMed: 38838750
DOI: 10.1016/j.envres.2024.119334 -
European Journal of Pharmacology Aug 2024Clinically, statins have long been used for the prevention and treatment of chronic renal diseases, however, the underlying mechanisms are not fully elucidated. The...
Clinically, statins have long been used for the prevention and treatment of chronic renal diseases, however, the underlying mechanisms are not fully elucidated. The present study investigated the effects of atorvastatin on diabetes renal injury and ferroptosis signaling. A mouse model of diabetes was established by the intraperitoneal injection of streptozotocin (50 mg/kg/day) plus a high fat diet with or without atorvastatin treatment. Diabetes mice manifested increased plasma glucose and lipid profile, proteinuria, renal injury and fibrosis, atorvastatin significantly lowered plasma lipid profile, proteinuria, renal injury in diabetes mice. Atorvastatin reduced renal reactive oxygen species (ROS), iron accumulation and renal expression of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), transferrin receptor 1 (TFR1), and increased renal expression of glutathione peroxidase 4 (GPX), nuclear factor erythroid 2-related factor (NRF) and ferritin heavy chain (FTH) in diabetes mice. Consistent with the findings in vivo, atorvastatin prevented high glucose-induced ROS formation and Fe accumulation, an increase in the expression of 4-HNE, MDA and TFR1, and a decrease in cell viability and the expression of NRF, GPX and FTH in HK cells. Atorvastatin also reversed ferroptosis inducer erastin-induced ROS production, intracellular Fe accumulation and the changes in the expression of above-mentioned ferroptosis signaling molecules in HK cells. In addition, atorvastatin alleviated high glucose- or erastin-induced mitochondria injury. Ferroptosis inhibitor ferrostatin-1 and antioxidant N-acetylcysteine (NAC) equally reversed the expression of high glucose-induced ferroptosis signaling molecules. Our data support the notion that statins can inhibit diabetes-induced renal oxidative stress and ferroptosis, which may contribute to statins protection of diabetic nephropathy.
Topics: Ferroptosis; Animals; Diabetic Nephropathies; Oxidative Stress; Atorvastatin; Male; Signal Transduction; Mice; Reactive Oxygen Species; Diabetes Mellitus, Experimental; Mice, Inbred C57BL; Humans; Kidney; Cell Line; Phenylenediamines
PubMed: 38825302
DOI: 10.1016/j.ejphar.2024.176699