How does atorvastatin work
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How Atorvastatin Works: Mechanisms and Effects
Inhibition of HMG-CoA Reductase
Atorvastatin is primarily known for its ability to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase. This enzyme is crucial in the biosynthesis of cholesterol in the liver. By blocking this enzyme, atorvastatin effectively reduces the production of cholesterol, leading to lower levels of low-density lipoprotein (LDL) cholesterol in the bloodstream 26.
Antioxidant and Anti-Inflammatory Effects
Oxidative Stress Reduction
Atorvastatin has been shown to reduce oxidative stress by increasing adiponectin levels, which in turn down-regulates NADPH oxidase. This enzyme is a significant source of reactive oxygen species (ROS) in the body. By lowering the levels of NADPH oxidase, atorvastatin reduces oxidative damage, which is beneficial for patients with hypercholesterolemia 1.
Anti-Inflammatory Properties
Atorvastatin also exhibits anti-inflammatory effects. It modulates the immune response by promoting a Th2 bias, which involves the secretion of anti-inflammatory cytokines like IL-4, IL-5, and IL-10, while suppressing pro-inflammatory cytokines such as IL-2, IL-12, and TNF-α. This shift helps in reducing inflammation in conditions like multiple sclerosis and other autoimmune diseases 7. Additionally, atorvastatin has been found to inhibit inflammatory angiogenesis by down-regulating VEGF, TNF-α, and TGF-β1 9.
Effects on Lipid Metabolism and Mitochondrial Function
Lipid Metabolism Regulation
Atorvastatin not only lowers cholesterol but also affects lipid metabolism by down-regulating miR-21, which leads to the upregulation of PPARα. This regulation helps in improving mitochondrial function and reducing lipid metabolism disorders, particularly in diabetic nephropathy 3. Furthermore, atorvastatin decreases fatty acid oxidation by inactivating the p-STAT3/CPT1 pathway, which helps in ameliorating mitochondrial dysfunction and cardiac hypertrophy 8.
Mitochondrial Function Improvement
By improving mitochondrial function, atorvastatin helps in reducing ROS production and restoring mitochondrial membrane potential. This is particularly beneficial in conditions characterized by mitochondrial dysfunction, such as diabetic nephropathy and cardiac hypertrophy 38.
Impact on Gut Microbiota and Intestinal Barrier
Atorvastatin has been shown to modulate the gut microbiota, increasing the abundance of beneficial bacteria like Firmicutes and Lactobacillus while decreasing harmful bacteria like Bacteroidetes. This modulation improves intestinal barrier function and reduces systemic inflammation, which is beneficial in conditions like ischemic stroke 4.
Hormonal Effects
Testosterone Levels
Atorvastatin can affect testosterone levels by reducing cholesterol, the precursor for steroid hormone synthesis. Studies have shown that atorvastatin may lower testosterone levels in females with polycystic ovary syndrome (PCOS) but does not significantly affect testosterone levels in males 510.
Conclusion
Atorvastatin is a multifaceted drug that not only lowers cholesterol levels by inhibiting HMG-CoA reductase but also exhibits antioxidant, anti-inflammatory, and lipid-regulating properties. It improves mitochondrial function, modulates gut microbiota, and can affect hormone levels, making it a versatile medication for various conditions beyond hypercholesterolemia.
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Most relevant research papers on this topic
Atorvastatin inhibits oxidative stress via adiponectin-mediated NADPH oxidase down-regulation in hypercholesterolemic patients.
Atorvastatin's antioxidant effect in hypercholesterolemic patients may be mediated by adiponectin-mediated NADPH oxidase down-regulation.
RCTClinical Pharmacokinetics of Atorvastatin
Atorvastatin effectively lowers LDL cholesterol levels, but its pharmacokinetics may be affected by factors such as food, drug interactions, and dietary factors.
Highly CitedAtorvastatin Restores PPARα Inhibition of Lipid Metabolism Disorders by Downregulating miR-21 Expression to Improve Mitochondrial Function and Alleviate Diabetic Nephropathy Progression
Atorvastatin inhibits renal tubular epithelial cell injury in type 1 diabetic mice by inhibiting miR-21 expression and restoring PPAR expression, promoting lipid metabolism homeostasis and restoring mitochondrial function.
Non-RCT
Animal StudyAtorvastatin alleviates microglia-mediated neuroinflammation via modulating the microbial composition and the intestinal barrier function in ischemic stroke mice.
Atorvastatin reduces microglia-mediated neuroinflammation in ischemic stroke mice by restoring gut microbiota, improving intestinal barrier function, and regulating intestinal immunity.
Non-RCTAnimal StudyEffect of atorvastatin on testosterone levels.
Atorvastatin has a small negative effect on testosterone levels in both males and females when compared to placebo or no treatment, but may have beneficial effects in the setting of polycystic ovary syndrome (PCOS).
Meta-Analysis
Very Rigorous JournalAtorvastatin
Atorvastatin effectively reduces LDL-cholesterol levels and may become a first-line treatment for patients with hypercholesterolaemia, particularly suitable for those with familial hypercholesterolaemia and combined hyperlipidaemia or hypertriglyceridaemia.
Highly CitedThe HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease
Atorvastatin may be beneficial for multiple sclerosis and other Th1-mediated autoimmune diseases by promoting a Th2 bias and reversing paralysis in central nervous system autoimmune diseases.
Non-RCTAnimal StudyHighly CitedAtorvastatin ameliorates lipid overload-induced mitochondrial dysfunction and myocardial hypertrophy by decreasing fatty acid oxidation through inactivation of the p-STAT3/CPT1 pathway.
Atorvastatin improves lipid overload-induced mitochondrial dysfunction and cardiac hypertrophy by decreasing fatty acid oxidation through the p-STAT3/CPT1 pathway, independent of lowering cholesterol levels.
Non-RCTAnimal Study
Rigorous JournalAtorvastatin inhibits inflammatory angiogenesis in mice through down regulation of VEGF, TNF-alpha and TGF-beta1.
Atorvastatin inhibits inflammatory angiogenesis in mice by downregulating VEGF, TNF-alpha, and TGF-beta1.
Non-RCTAnimal StudyHighly CitedEffect of atorvastatin on testosterone levels.
Atorvastatin may reduce testosterone levels in males and females, but its effects on testosterone levels in PCOS patients may be beneficial.
Meta-AnalysisVery Rigorous Journal