Causes Underlying the Reduced Response to Simvastatin Treatment in Hypercholesterolemic Patients

1993 ◽  
pp. 207-229
Author(s):  
Alberto Corsini ◽  
Maria Mazzotti ◽  
Tiziano Zanelli ◽  
Patrizia Uboldi ◽  
Domenico Sommariva ◽  
...  
Keyword(s):  
Simvastatin Treatment

PHOSPHO1 Gene DNA Methylations are Associated with a Change in HDL-C Response to Simvastatin Treatment

2020 ◽  
Vol 26 (38) ◽  
pp. 4944-4952 ◽  
Author(s):  
Juanlin Fan ◽  
Qianru Cai ◽  
Di Zhang ◽  
Justin Weinstock ◽  
Xiaoxiao Qu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Density Lipoprotein ◽  
Significant Negative Correlation ◽  
High Response ◽  
Lipid Lowering ◽  
Additive Interaction ◽  
Simvastatin Treatment ◽  
Obese Subjects ◽  
Dna Methylations ◽  
Response Group

Objective: Our aim was to detect the effects of DNA methylations in the phosphoethanolamine/ phosphocholine phosphatase (PHOSPHO1) gene on the therapeutic efficacy of simvastatin. Methods: We used an extreme sampling approach by selecting 211 individuals from approximately the top and bottom 15% of adjusted lipid-lowering response residuals to simvastatin (n=104 for the high response group and n=107 for the low response group) from a total of 734 subjects with hyperlipidemia. They received a daily oral dose of 20 mg simvastatin for eight consecutive weeks. DNA methylation loci at the PHOSPHO1 gene were measured using high-throughput next-generation sequencing-based sequencing technology. Fasting serum lipids were measured at baseline and after eight weeks of simvastatin treatment. Results: Mean PHOSPHO1 DNA methylation had a significant negative correlation with high-density lipoprotein cholesterol (HDL-C) variation (β=-0.014, P=0.045) in the high response group. After stratifying by body mass index (BMI), the associations between the PHOSPHO1 DNA methylations and the change in HDL-C in response to simvastatin were more significant in obese subjects with a BMI of 25 kg/m2 or higher (β=-0.027, P=0.002). Mean PHOSPHO1 methylation and traditional predictors could explain up to 24.7% (adjusted R2) of the change in HDL-C response in obese patients. There was a statistically significant additive interaction term (P=0.028) between BMI and mean PHOSPHO1 methylation in the model of the change in HDL-C in response to simvastatin. Conclusion: Our findings suggest that PHOSPHO1 DNA methylations are associated with a change in HDL-C in response to simvastatin treatment, and this association is especially dependent on the extent of patient obesity.

scholarly journals Effect of Donor Simvastatin Treatment on Gene Expression Profiles in Human Cardiac Allografts during Reperfusion

2021 ◽  
Vol 40 (4) ◽  
pp. S123-S124
Author(s):  
R. Krebs ◽  
E. Holmström ◽  
K. Dhaygude ◽  
M. Kankainen ◽  
S. Syrjälä ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Simvastatin Treatment ◽  
Cardiac Allografts

scholarly journals Simvastatin Improves the Jaw Bone Microstructural Defect Induced by High Cholesterol Diet in Rats by Regulating Autophagic Flux

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Jianhua Zhou ◽  
Xiaoli Gao ◽  
Shengyun Huang ◽  
Li Ma ◽  
Yanjun Cui ◽  
...  
Keyword(s):  
High Cholesterol Diet ◽  
Autophagic Flux ◽  
Cholesterol Diet ◽  
Sprague Dawley ◽  
High Cholesterol ◽  
Trabecular Thickness ◽  
Simvastatin Treatment ◽  
Jaw Bone ◽  
Microstructural Defect ◽  
Sprague Dawley Rats

Objective. The objective of this study is to evaluate the effect of simvastatin on the jaw bone microstructural defect and autophagy in rats with high cholesterol diet (HCD). Methods. Male Sprague-Dawley rats were fed a standard rodent chow (NC group) or a high cholesterol diet for 32 weeks and the HCD-fed rats were treated with vehicle (HC group) or simvastatin (5 mg/kg orally daily for 8 weeks, HC + SIM group, and n=10/group). The static histomorphometric changes in the jaw bone tissues in individual rats were evaluated. The relative levels of OPG, RANKL, NF-κB, LC3, and p62 in the jaw bone tissues were determined by quantitative RT-PCR and/or immunohistochemistry. Results. Compared with the NC group, the HC groups had lower trabecular bone volume, trabecular thickness and trabecular number, and increased ratios of RANKL/OPG in the jaw bone, accompanied by enhanced NF-κB activation and autophagy. Simvastatin treatment inhabited these changes, including the decreased levels of serum proinflammatory cytokines and increased autophagy. Conclusion. Simvastatin treatment could inhibit the hyperlipidemia-induced jaw bone microstructural defect in rats by increasing autophagic flux.

Testicular Function in Hypercholesterolemic Male Patients During Prolonged Simvastatin Treatment

1996 ◽  
Vol 28 (04) ◽  
pp. 193-198 ◽  
Author(s):  
Clorinda Azzarito ◽  
L. Boiardi ◽  
W. Vergoni ◽  
M. Zini ◽  
I. Portioli
Keyword(s):  
Testicular Function ◽  
Simvastatin Treatment ◽  
Male Patients

scholarly journals Nurr1 modulation mediates neuroprotective effects of statins

2021 ◽  
Author(s):  
Sabine Willems ◽  
Whitney Kilu ◽  
Giuseppe Faudone ◽  
Jan Heering ◽  
Daniel Merk
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Gene Expression Analysis ◽  
Energy Utilization ◽  
Neuroprotective Effects ◽  
Simvastatin Treatment ◽  
Differential Gene Expression Analysis ◽  
Functional Studies ◽  
Promising Therapeutic Target ◽  
Differential Gene

AbstractThe ligand-sensing transcription factor Nurr1 emerges as a promising therapeutic target for neurodegenerative pathologies but Nurr1 ligands for functional studies and therapeutic validation are lacking. Here we report pronounced Nurr1 modulation by statins for which clinically relevant neuroprotective effects have been demonstrated. Several statins directly affected Nurr1 activity in cellular and cell-free settings with low micromolar to sub-micromolar potencies. Simvastatin exhibited anti-inflammatory effects in astrocytes which were abrogated by Nurr1 knockdown. Differential gene expression analysis in native and Nurr1 silenced cells revealed strong proinflammatory effects of Nurr1 knockdown while simvastatin treatment induced several neuroprotective mechanisms via Nurr1, for example, in energy utilization and reduced apoptosis. These findings suggest Nurr1 involvement in the well-documented but mechanistically elusive neuroprotection by statins.

scholarly journals Prophylactic benefits of systemically delivered simvastatin treatment in a house dust mite challenged murine model of allergic asthma

2018 ◽  
Vol 175 (7) ◽  
pp. 1004-1016 ◽  
Author(s):  
Aruni Jha ◽  
Min H Ryu ◽  
Ojo OO ◽  
Hilary J Bews ◽  
Jules C Carlson ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
House Dust ◽  
House Dust Mite ◽  
Murine Model ◽  
Simvastatin Treatment ◽  
Dust Mite

Abstract 194: Cognitive Outcome in Acute Simvastatin Treatment for Aneurysmal Subarachnoid Hemorrhage

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
George Wong ◽  
Keyword(s):  
Cognitive Impairment ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Infarction ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Primary Outcome Measure ◽  
Cognitive Outcomes ◽  
Cognitive Outcome ◽  
Secondary Outcome ◽  
Modified Rankin Scale ◽  
Simvastatin Treatment

Objectives: Experimental evidence has indicated the benefit of simvastatin in the treatment of subarachnoid haemorrhage (SAH). Recently, acute simvastatin treatment was not shown to be beneficial in neurological outcome using modified Rankin Scale. Cognitive function is another important dimension of outcome assessment and yet had not been investigated in statin studies for aneurysmal subarachnoid hemorrhage. We therefore explored whether acute simvastatin treatment would improve cognitive outcomes. Methods: The study recruited SAH patients with acute simvastatin treatment enrolled in a randomized controlled double-blinded clinical trial (ClinicalTrials.gov Identifier: NCT01038193). A control cohort of SAH patients without simvastatin treatment was identified with propensity score matching of age and admission grade. Primary outcome measure was Montreal Cognitive Assessment (MoCA). Secondary outcome measures were delayed ischaemic deficit (DID), delayed cerebral infarction, modified Rankin Scale (mRS), and Mini-Mental State Examination( MMSE). Results: Fifty-one SAH patients with acute simvastatin treatment and 51 SAH patients without simvastatin treatment were recruited for analysis. At 3 months, there were no differences in MoCA scores (MoCA: 21+/-6 vs. 21+/-5, p=0.772). MoCA-assessed cognitive impairment (MoCA<26) was not different (75% vs. 80%, OR 0.7, 95%CI 0.3 to 1.8, p=0.477). There were also no differences in DID, delayed cerebral infarction, favorable mRS outcome, and MMSE scores, and MMSE-assessed cognitive impairment between both groups. Conclusions: The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage.

Endogenous miR-21 and TIMP-1 Regulate Hepatic Injury and Fibrosis by Bile Duct Ligation in Vivo

2021 ◽  
Author(s):  
Chung-Hsin Lee ◽  
Yi-Chin Yang ◽  
Yi-Wen Hung ◽  
Ching-Chang Cheng ◽  
Yen-Chung Peng
Keyword(s):  
Bile Duct ◽  
Large Scale ◽  
Bile Duct Ligation ◽  
Inflammatory Responses ◽  
Histopathological Examination ◽  
Sprague Dawley ◽  
Functional Protein ◽  
Common Bile Duct Ligation ◽  
Simvastatin Treatment ◽  
Duct Ligation

Abstract TIMP metallopeptidase inhibitor 1 (TIMP-1) has been identified as a multifunctional molecule with divergent functions. It participates in wound healing and regeneration, cell morphology and survival, tumor metastasis, angiogenesis, and inflammatory responses. An imbalance of Matrix Metalloproteinase/TIMP regulation has been implicated in several inflammatory diseases. TIMP-1 could be considered an important regulator in the process of liver fibrosis and bile duct degeneration. Thus, we aimed to determine the role of TIMP-1 in a rat model of Common Bile Duct Ligation (CBDL). Male Sprague-Dawley rats were divided into several groups, including those with/ without CBDL surgery and those with/without amiodarone or simvastatin administration. Amiodarone/simvastatin treatment was given at a daily dose of 15 mg/kg and 18 mg/kg by means of intergalactic gavage, which began 7 days prior to CBDL induction. Two weeks after surgery, the animals in each group were sacrificed and hepatocyte degeneration severity was examined using histological morphologies. Large-scale array for secretory factors is intended for the purpose of finding key functional protein after CBDL. The hepatic level of miR-21 was determined through Taqman miRNA analysis. Furthermore, the TIMP-1 level in liver tissue was also visualized by histological stain. Liver injury and fibrosis were founded in CBDL rats based upon histopathological examination and serum biochemical analysis. Hepatic miR-21 and TIMP-1 were significantly up-regulated in CBDL rats, while being slightly rescued in response to amiodarone or simvastatin treatment. Up-regulation of miR-21 and TIMP-1 may result in the progression of hepatic cirrhosis after bile duct obstruction. Drug intervention for cirrhosis, like the use of statin, may function via similar mechanisms.

Timing of simvastatin treatment: Authors' reply

BMJ ◽  
2004 ◽  
Vol 328 (7432) ◽  
pp. 168-a-168
Author(s):  
A. Wallace
Keyword(s):  
Simvastatin Treatment
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