- Influence of risk factors on insulin resistance in patients with overweight and obesity. [Journal Article]
- WLWiad Lek 2018; 71(3 pt 1):558-560
- CONCLUSIONS: Conclusions: We assume that modification of lifestyle and individual approach to pharmacologic correction of dyslipidemia in overweight and obese patients help to avoid the development of insulin resistance, which is a predictor of type 2 diabetes mellitus.
- Antiglycation study of HMG-R inhibitors and tocotrienol against glycated BSA and LDL: A comparative study. [Journal Article]
- IJInt J Biol Macromol 2018 May 18
- Non-enzymatic glycation mediated advanced glycation end products (AGEs) generation results in the pathogenesis of diabetic complications and atherosclerotic cardiovascular disease (ASCVD) which is gr...
Non-enzymatic glycation mediated advanced glycation end products (AGEs) generation results in the pathogenesis of diabetic complications and atherosclerotic cardiovascular disease (ASCVD) which is greatly influenced by 3-hydroxy-3-methyl-glutaryl Co-A reductase (HMG-R) activity. HMG-R inhibitors, statins, are well known for reducing mortality and morbidity of ASCVD in patients with diabetes due to their pleiotropic effects independent of cholesterol lowering. Due to distinct chemical structures, various statins may play important role in the inhibition of AGEs mediated pathologies. Herein, we evaluated the anti-glycating potential of atorvastatin (AT), rosuvastatin (RT), pitavastatin (PT), fluvastatin (FT), simvastatin (ST) alone as well in combination with ezetimibe (EZ) and tocotrienol (TT) against d-ribose mediated BSA and LDL glycation by various physicochemical approaches. Our data suggested that AT, TT, RT, EZ, EZ-AT, and EZ-RT were able to substantially inhibit the AGEs formation via modulation of hyperchromicity, fluorogenic AGEs, % contribution of α-helix and β-sheets to protein secondary structure, amide-I band stretching, carbonyl and HMF content in Gly-BSA as well as Gly-LDL. On the basis of above findings, we concluded that HMG-R inhibitors and TT, alone or in combination with EZ, may be established as terrific therapeutic agents for the patients suffering from AGEs induced diabetic cum ASCVD complications.
- Variations in time to benefit among clinical trials of cholesterol-lowering drugs. [Journal Article]
- JCJ Clin Lipidol 2018 Apr 21
- CONCLUSIONS: TTB is variable among trials of cholesterol-lowering drugs, being shorter with statin compared to nonstatin drugs. TTB is shorter with atorvastatin than with other statins. For trials of new cholesterol-lowering drugs, outcome curves that do not separate for up to 30 months do not preclude eventual benefit.
- Protective effect of atorvastatin meditated by HMGCR gene on diabetic rats with atherosclerosis: An in vivo and in vitro study. [Journal Article]
- BPBiomed Pharmacother 2018 May 15; 104:240-251
- CONCLUSIONS: The key findings of the present study suggested that the protective effect conferred by AVT in diabetic rats with atherosclerosis was associated with the overexpression of the HMGCR gene, thus presenting a novel target for atherosclerosis treatment.
- Atorvastatin Inhibits Inflammatory Response, Attenuates Lipid Deposition, and Improves the Stability of Vulnerable Atherosclerotic Plaques by Modulating Autophagy. [Journal Article]
- FPFront Pharmacol 2018; 9:438
- Atherosclerosis is a chronic disease comprising intima malfunction and arterial inflammation. Recent studies have demonstrated that autophagy could inhibit inflammatory response in atherosclerosis an...
Atherosclerosis is a chronic disease comprising intima malfunction and arterial inflammation. Recent studies have demonstrated that autophagy could inhibit inflammatory response in atherosclerosis and exert subsequent atheroprotective effects. Our previous study also demonstrated the role of autophagy in the inhibition of inflammation by atorvastatin in vitro. Therefore, in the present study, we aimed to determine whether atorvastatin could upregulate autophagy to inhibit inflammatory cytokines secretion, lipid accumulation, and improve vulnerable plaque stability, both in vitro and in vivo. First, we established a vulnerable atherosclerotic plaque mouse model through partial ligation of left common carotid artery and left renal artery to explore the effect of atorvastatin on vulnerable plaques. The results showed that atorvastatin could enhance the stability of vulnerable atherosclerotic plaques and reduce the lesion area in the aorta. Atorvastatin could also inhibit NLRP3 inflammasome activation and inflammatory cytokines, such as IL-1β, TNF-α, and IL-18 secretion in vivo. Atorvastatin treatment upregulated the expression of autophagy-related protein microtubule-associated protein light chain (LC3B) and downregulated the expression of SQSTM1/p62, which suggested that autophagy was activated in vulnerable plaques. Transmission electron microscopy further demonstrated the atorvastatin-induced increase in autophagy activity in vulnerable atherosclerotic plaques. We employed oxidized low-density lipoprotein (ox-LDL) to stimulate RAW264.7 cells with atorvastatin, which showed that atorvastatin could attenuate lipid deposition, ameliorate inflammation, inhibit NLRP3 inflammasome activation, and enhance autophagy in vitro. All these beneficial effects were abolished by 3-methyladenine treatment, an autophagy inhibitor. Atorvastatin also significantly inhibited the phosphorylation of mTOR, which strongly suggested the involvement of the mTOR pathway. Our study proposed a new role for atorvastatin as an autophagy inducer to exert anti-inflammatory and atheroprotective effects, to stabilize vulnerable atherosclerotic plaques.
- Partially Purified Aqueous Fraction of Desmodium gyrans DC Improves Reverse Cholesterol Transport and Lipoprotein Metabolism in Wistar Rats Fed with High Fat Diet. [Journal Article]
- JEJ Environ Pathol Toxicol Oncol 2018; 37(1):27-41
- Apart from the conventional hypolipidemic therapy, plaque regression through enhanced reverse cholesterol transport (RCT) has emerged as novel approach in atherosclerotic drug development. High-densi...
Apart from the conventional hypolipidemic therapy, plaque regression through enhanced reverse cholesterol transport (RCT) has emerged as novel approach in atherosclerotic drug development. High-density lipoprotein (HDL) mimetics as well as agents that augment the functional HDL and RCT pathways are under intense exploration. Desmodium gyrans (Fabacea) has been shown to have hypolipidemic efficacy, with an HDL-enhancing property. In this study, a chromatographically purified active fraction of D. gyrans (DGMAF) significantly decreased the serum and lipid profiles as well as lipotoxicity in liver in Wistar rats fed with high-fat diet (HFD). Except for the marginal deposition of liver lipids, all other organs showed no weight gain due to lipid accumulation. A lower level of lipid peroxidation and a reduced atherogenic index suggests the hypolipidemic efficacy of DGMAF, which was comparatively higher than clinically used atorvastatin. Furthermore, the DGMAF-treated animals had enhanced levels of HDL, associated ApoA-1, and paraoxonase activity. The mRNA levels of ApoA-1 and SR-B1 were upregulated, and cholesteryl ester transfer protein (CETP) was downregulated. Overall, the results of this study indicate that D. gyrans augments the RCT pathway and improves the lipid metabolism in rats fed an HFD.
- Pathophysiology and non-surgical treatment of chronic subdural hematoma: from past to present to future. [Review]
- WNWorld Neurosurg 2018 May 14
- CONCLUSIONS: Based on pathophysiological mechanisms, animal experiments and small patient studies medical treatment may play a role in the treatment of CSDH. There is a lack of level I evidence in the non-surgical treatment of CSDH. Therefore, randomized controlled trials, currently lacking, are needed to assess what treatment is most effective in each individual patient.
- Rosuvastatin and atorvastatin preserve renal function in HIV-1-infected patients with chronic kidney disease and hyperlipidaemia. [Journal Article]
- HCHIV Clin Trials 2018; 19(3):120-128
- CONCLUSIONS: In our study, rosuvastatin and atorvastatin showed a significant protective effect on the renal function compared to omega-3 fatty acids in HIV-1-infected patients with CKD and dyslipidaemia.
- Effects and potential mechanism of atorvastatin treatment on Lp-PLA2 in rats with dyslipidemia. [Journal Article]
- AMArch Med Sci 2018; 14(3):629-634
- CONCLUSIONS: Atorvastatin treatment is beneficial for reducing the Lp-PLA2 level in rats with dyslipidemia, which may be related to reduced ROCK1 expression in a dose-dependent manner.
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- Lipophilic statins limit cancer cell growth and survival, via involvement of Akt signaling. [Journal Article]
- PlosPLoS One 2018; 13(5):e0197422
- The HMG-CoA reductase inhibitors, statins, have been used as lipid lowering drugs for decades and several epidemiological studies suggest statin usage correlates with a decreased incidence of cancer ...
The HMG-CoA reductase inhibitors, statins, have been used as lipid lowering drugs for decades and several epidemiological studies suggest statin usage correlates with a decreased incidence of cancer specific mortality in patients. However, the mechanism of this mortality benefit remains unclear. Here, we demonstrate that statin drug lipophilicity and affinity for its target enzyme, HMGCR, determine their growth suppressive potency against various tumor cell lines. The lipophilic atorvastatin decreases cancer cell proliferation and survival in vitro. Statin sensitivity coincided with Ras localization to the cytosol instead of the membrane, consistent with a decrement in prenylation. To investigate signaling pathways that may be involved with sensitivity to statin therapy, we employed inhibitors of the PI3K-Akt and Mek-Erk signaling cascades. We found that inhibition of PI3K signaling through Akt potentiated statin sensitivity of breast cancer cells in vitro and in co-culture with primary human hepatocytes. The same effect was not observed with inhibition of Mek signaling through Erk. Moreover, the sensitivity of breast cancer cells to atorvastatin-mediated growth suppression correlated with a decrease in EGF-mediated phosphorylation of Akt. As an increase in Akt activity has been shown to be involved in the metastasis and metastatic outgrowth of many cancer types (including breast), these data suggest a mechanism by which statins may reduce cancer specific mortality in patients.