1.Exploring the Genetic Associations Between the Use of Statins and Alzheimer's Disease
Jibeom LEE ; Suhyeon PARK ; Yumin KIM ; Hyun Min KIM ; Chang-Myung OH
Journal of Lipid and Atherosclerosis 2022;11(2):133-146
Objective:
Alzheimer's disease (AD) is the most common cause of dementia. The statins have shown beneficial effects on cognitive functions and reduced the risk of dementia development. However, the exact mechanisms of statin effects in AD are not yet fully understood. In this study, we aimed to explore the underlying mechanisms of statin on AD.
Methods:
We downloaded AD blood dataset (GSE63060) and statin-related blood gene expression dataset (GSE86216). Then we performed gene expression analysis of each dataset and compared blood gene expressions between AD patients and statin-treated patients. Then, we downloaded mouse embryonic neural stem cell dataset (GSE111945) and performed gene expression analysis.
Results:
From the human blood dataset, we identified upregulated/downregulated genes in AD patients and statin-treated patients. Some of the upregulated genes (AEN, MBTPS1, ABCG1) in the blood of AD patients are downregulated in statin-treated patients. Several downregulated genes (FGL2, HMGCS1, PSME2, SRSF3, and ATG3) are upregulated in statintreated patients. Gene set enrichment analysis using mouse stem cell dataset revealed a significant relationship of Kyoto Encyclopedia of Genes and Genomes-defined pathway of AD in statin-treated neural stem cells compared to vehicle-treated neural stem cells (normalized enrichment score: −2.24 in male and −1.6 in female).
Conclusion
These gene expression analyses from human blood and mouse neural stem cell demonstrate the important clues on the molecular mechanisms of impacts of statin on AD disease. Further studies are needed to investigate the exact role of candidate genes and pathways suggested in our AD pathogenesis study.
2.Pharmacologic Activation of Angiotensin-Converting Enzyme II Alleviates Diabetic Cardiomyopathy in db/db Mice by Reducing Reactive Oxidative Stress
Donghyun KIM ; Wooju JEONG ; Yumin KIM ; Jibeom LEE ; Sung Woo CHO ; Chang-Myung OH ; Raekil PARK
Diabetes & Metabolism Journal 2023;47(4):487-499
Background:
Diabetes mellitus is one of the most common chronic diseases worldwide, and cardiovascular disease is the leading cause of morbidity and mortality in diabetic patients. Diabetic cardiomyopathy (DCM) is a phenomenon characterized by a deterioration in cardiac function and structure, independent of vascular complications. Among many possible causes, the renin-angiotensin-aldosterone system and angiotensin II have been proposed as major drivers of DCM development. In the current study, we aimed to investigate the effects of pharmacological activation of angiotensin-converting enzyme 2 (ACE2) on DCM.
Methods:
The ACE2 activator diminazene aceturate (DIZE) was administered intraperitoneally to male db/db mice (8 weeks old) for 8 weeks. Transthoracic echocardiography was used to assess cardiac mass and function in mice. Cardiac structure and fibrotic changes were examined using histology and immunohistochemistry. Gene and protein expression levels were examined using quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Additionally, RNA sequencing was performed to investigate the underlying mechanisms of the effects of DIZE and identify novel potential therapeutic targets for DCM.
Results:
Echocardiography revealed that in DCM, the administration of DIZE significantly improved cardiac function as well as reduced cardiac hypertrophy and fibrosis. Transcriptome analysis revealed that DIZE treatment suppresses oxidative stress and several pathways related to cardiac hypertrophy.
Conclusion
DIZE prevented the diabetes mellitus-mediated structural and functional deterioration of mouse hearts. Our findings suggest that the pharmacological activation of ACE2 could be a novel treatment strategy for DCM.
3.Efficacy and Safety of the New Appetite Suppressant, Liraglutide: A Meta-Analysis of Randomized Controlled Trials
Shinje MOON ; Jibeom LEE ; Hye Soo CHUNG ; Yoon Jung KIM ; Jae Myung YU ; Sung Hoon YU ; Chang-Myung OH
Endocrinology and Metabolism 2021;36(3):647-660
Background:
Obesity is a chronic disease associated with metabolic diseases such as diabetes and cardiovascular disease. Since the U.S. Food and Drug Administration approved liraglutide as an anti-obesity drug for nondiabetic patients in 2014, it has been widely used for weight control in overweight and obese people. This study aimed to systematically analyze the effects of liraglutide on body weight and other cardiometabolic parameters.
Methods:
We investigated articles from PubMed, EMBASE, and the Cochrane Library to search randomized clinical trials that examined body weight changes with liraglutide treatment.
Results:
We included 31 studies with 8,060 participants for this meta-analysis. The mean difference (MD) between the liraglutide group and the placebo group was −4.19 kg (95% confidence interval [CI], −4.84 to −3.55), with a −4.16% change from the baseline (95% CI, −4.90 to −3.43). Liraglutide treatment correlated with a significantly reduced body mass index (MD: −1.55; 95% CI, −1.76 to −1.34) and waist circumference (MD: −3.11 cm; 95% CI, −3.59 to −2.62) and significantly decreased blood pressure (systolic blood pressure, MD: −2.85 mm Hg; 95% CI, −3.36 to −2.35; diastolic blood pressure, MD: −0.66 mm Hg; 95% CI, −1.02 to −0.30), glycated hemoglobin (MD: −0.40%; 95% CI, −0.49 to −0.31), and low-density lipoprotein cholesterol (MD: –2.91 mg/dL; 95% CI, −5.28 to −0.53; MD: −0.87% change from baseline; 95% CI, −1.17 to −0.56).
Conclusion
Liraglutide is effective for weight control and can be a promising drug for cardiovascular protection in overweight and obese people.
4.Efficacy and Safety of the New Appetite Suppressant, Liraglutide: A Meta-Analysis of Randomized Controlled Trials
Shinje MOON ; Jibeom LEE ; Hye Soo CHUNG ; Yoon Jung KIM ; Jae Myung YU ; Sung Hoon YU ; Chang-Myung OH
Endocrinology and Metabolism 2021;36(3):647-660
Background:
Obesity is a chronic disease associated with metabolic diseases such as diabetes and cardiovascular disease. Since the U.S. Food and Drug Administration approved liraglutide as an anti-obesity drug for nondiabetic patients in 2014, it has been widely used for weight control in overweight and obese people. This study aimed to systematically analyze the effects of liraglutide on body weight and other cardiometabolic parameters.
Methods:
We investigated articles from PubMed, EMBASE, and the Cochrane Library to search randomized clinical trials that examined body weight changes with liraglutide treatment.
Results:
We included 31 studies with 8,060 participants for this meta-analysis. The mean difference (MD) between the liraglutide group and the placebo group was −4.19 kg (95% confidence interval [CI], −4.84 to −3.55), with a −4.16% change from the baseline (95% CI, −4.90 to −3.43). Liraglutide treatment correlated with a significantly reduced body mass index (MD: −1.55; 95% CI, −1.76 to −1.34) and waist circumference (MD: −3.11 cm; 95% CI, −3.59 to −2.62) and significantly decreased blood pressure (systolic blood pressure, MD: −2.85 mm Hg; 95% CI, −3.36 to −2.35; diastolic blood pressure, MD: −0.66 mm Hg; 95% CI, −1.02 to −0.30), glycated hemoglobin (MD: −0.40%; 95% CI, −0.49 to −0.31), and low-density lipoprotein cholesterol (MD: –2.91 mg/dL; 95% CI, −5.28 to −0.53; MD: −0.87% change from baseline; 95% CI, −1.17 to −0.56).
Conclusion
Liraglutide is effective for weight control and can be a promising drug for cardiovascular protection in overweight and obese people.