Short telomere subtelomeric hypomethylation is associated with telomere attrition in elderly diabetic patients

2019 ◽  
Vol 97 (4) ◽  
pp. 335-339 ◽  
Author(s):  
Naoki Makino ◽  
Toyoki Maeda ◽  
Nobuyuki Abe
Keyword(s):  
Methylation Status ◽  
Statin Treatment ◽  
Diabetic Patients ◽  
Short Telomere ◽  
Telomere Shortening ◽  
Telomere Attrition ◽  
Reductase Inhibitors ◽  
Hmg Coa Reductase Inhibitors ◽  
Coa Reductase

Telomere shortening is well known to be associated with the aging process and aging-associated diseases, including diabetes. The telomere length and subtelomeric methylation status in peripheral leucocytes (LTL) were compared in elderly type 2 diabetes (T2D) patients and diabetes-free controls (C). The methylation status was analyzed between MspI-TRF lengths and HpaII-TRF lengths by using methylation-sensitive and -insensitive restriction enzyme isoschizomers, MspI and HpaII, respectively. The mean telomere lengths, MspI-TRF or HpaII-TRF, were not significantly different between C and T2D patients. The percentage of fractionated densitometry showed that long and middle telomeres (>9.4 kb, 4.4–9.4 kb) were unaltered but short telomeres (<4.4 kb) in T2D patients were increased compared with C group. The methylation status revealed subtelomeric hypomethylation in short telomeres of T2D patients. When some patients with T2D were treated with 3-hydroxy-3-methylglutaril coenzyme A (HMG-CoA) reductase inhibitors (statin), results seen in short telomere of T2D patients were not observed and were not different from C. This suggested that this altered subtelomeric hypomethylation may be associated with the accelerated telomere shortening in elderly diabetic patients. These results also mean that the subtelomeric hypomethylation can also be influenced by statin treatment in T2D.

The effects of pemafibrate in Japanese patients with type 2 diabetes receiving HMG-CoA reductase inhibitors

2020 ◽  
Vol 20 ◽  
Author(s):  
Masataka Kusunoki ◽  
Takahiko Sakazaki ◽  
Kazuhiko Tsutsumi ◽  
Tetsuro Miyata ◽  
Yoshiharu Oshida
Keyword(s):  
Type 2 Diabetes ◽  
Combination Therapy ◽  
Hepatic Dysfunction ◽  
Combination Group ◽  
Hmg Coa Reductase ◽  
Reductase Inhibitors ◽  
Hmg Coa Reductase Inhibitors ◽  
Coa Reductase ◽  
Diabetes Patients

Objective: The combination therapy of HMG-CoA reductase inhibitors (statins), which are anti-hyperlipidemia agents, and fibrates may increase the risk of hepatic dysfunction and myopathy, so this combination required careful administration for patients. In the present study, we evaluated the effects of combination therapy of pemafibrate, a novel fibrate and statins. Methods: We administered pemafibrate for 6 months as an add-on to statin therapy in 27 type 2 diabetes patients with dyslipidemia already receiving statins for 6 months (combination group), and examined the efficacy and safety of the combination therapy in comparison with a pemafibrate monotherapy group. Results: In the combination group, decrease in serum total cholesterol levels was observed after 6 months of pemafibrate treatment compared to baseline, along with increase in HDL-cholesterol. While serum triglyceride level reduced, HbA1c level was elevated in both the groups. Serum creatinine kinase level, which is an indicator of myopathy, was lowered in the combination group. In addition, decrease in -glutamyl transpeptidase, a parameter of hepatic dysfunction, was observed in the combination group. Conclusion: The statin-pemafibrate combination therapy in type 2 diabetes patients with dyslipidemia improved lipid metabolism safely without increasing the risk of hepatic dysfunction and myopathy.

scholarly journals Influence of rosuvastatin treatment on cerebral inflammation and nitro-oxidative stress in experimental lung injury in pigs

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jens Kamuf ◽  
Andreas Garcia Bardon ◽  
Alexander Ziebart ◽  
Robert Ruemmler ◽  
Johannes Schwab ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Injury ◽  
Statin Treatment ◽  
Laboratory Animals ◽  
Reductase Inhibitors ◽  
Before And After ◽  
Standardized Treatment ◽  
Hmg Coa Reductase Inhibitors ◽  
Cerebral Inflammation ◽  
Coa Reductase

Abstract Background Many patients with acute respiratory distress syndrome (ARDS) suffer from cognitive impairment after hospital discharge. Different mechanisms have been implicated as potential causes for this impairment, inter alia cerebral inflammation. A class of drugs with antioxidant and anti-inflammatory properties are β-HMG-CoA-reductase inhibitors (“statins”). We hypothesized that treatment with rosuvastatin attenuates cerebral cytokine mRNA expression and nitro-oxidative stress in an animal model of acute lung injury. Methods After approval of the institutional and state animal care committee, we performed this prospective randomized controlled animal study in accordance with the international guidelines for the care and use of laboratory animals. Thirty-two healthy male pigs were randomized to one of four groups: lung injury by central venous injection of oleic acid (n = 8), statin treatment before and directly after lung injury (n = 8), statin treatment after lung injury (n = 8), or ventilation-only controls (n = 8). About 18 h after lung injury and standardized treatment, the animals were euthanised, and the brains and lungs were collected for further examinations. We determined histologic lung injury and cerebral and pulmonal cytokine and 3-nitrotyrosine production. Results We found a significant increase in hippocampal IL-6 mRNA after lung injury (p < 0.05). Treatment with rosuvastatin before and after induction of lung injury led to a significant reduction of hippocampal IL-6 mRNA (p < 0.05). Cerebral 3-nitrotyrosine was significantly higher in lung-injured animals compared with all other groups (p < 0.05 vs. animals treated with rosuvastatin after lung injury induction; p < 0.001 vs. all other groups). 3-Nitrotyrosine was also increased in the lungs of the lung-injured pigs compared to all other groups (p < 0.05 each). Conclusions Our findings highlight cerebral cytokine production and nitro-oxidative stress within the first day after induction of lung injury. The treatment with rosuvastatin reduced IL-6 mRNA and 3-nitrotyrosine concentration in the brains of the animals. In earlier trials, statin treatment did not reduce mortality in ARDS patients but seemed to improve quality of life in ARDS survivors. Whether this is attributable to better cognitive function because of reduced nitro-oxidative stress and inflammation remains to be elucidated.

scholarly journals A Possible Role for HMG-CoA Reductase Inhibitors and Its Association with HMGCR Genetic Variation in Parkinson’s Disease

2021 ◽  
Vol 22 (22) ◽  
pp. 12198
Author(s):  
Anna Pierzchlińska ◽  
Marek Droździk ◽  
Monika Białecka
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Statin Treatment ◽  
Neuroprotective Effects ◽  
Hmg Coa Reductase ◽  
Brain Functions ◽  
Reductase Inhibitors ◽  
Culture Models ◽  
Hmg Coa Reductase Inhibitors ◽  
Coa Reductase

Parkinson’s disease (PD) is the second most common neurodegenerative disease characterised by both motor- and non-motor symptoms, including cognitive impairment. The aetiopathogenesis of PD, as well as its protective and susceptibility factors, are still elusive. Neuroprotective effects of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors—statins—via both cholesterol-dependent and independent mechanisms have been shown in animal and cell culture models. However, the available data provide conflicting results on the role of statin treatment in PD patients. Moreover, cholesterol is a vital component for brain functions and may be considered as protective against PD. We present possible statin effects on PD under the hypothesis that they may depend on the HMG-CoA reductase gene (HMGCR) variability, such as haplotype 7, which was shown to affect cholesterol synthesis and statin treatment outcome, diminishing possible neuroprotection associated with HMG-CoA reductase inhibitors administration. Statins are among the most prescribed groups of drugs. Thus, it seems important to review the available data in the context of their possible neuroprotective effects in PD, and the HMG-CoA reductase gene’s genetic variability.

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