Journal of Lipid and Atherosclerosis最新文献

{"title":"Clinical Characteristics of Patients With Statin Discontinuation in Korea: A Nationwide Population-Based Study.","authors":"Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park","doi":"10.12997/jla.2024.13.1.41","DOIUrl":"10.12997/jla.2024.13.1.41","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the clinical characteristics of patients with statin discontinuation in Korea, using a nationwide database.</p><p><strong>Methods: </strong>We analyzed 1,308,390 patients treated with statin for the first time in their life between 2016 and 2017 using the Korean National Health Information Database. The patients participated in the Korean National Health Screening Program within two years before taking statin. Patients with statin discontinuation were defined as those who were not prescribed statin between 365 days and 730 days after the initial statin prescription.</p><p><strong>Results: </strong>The overall prevalence of statin discontinuation was 39.44%. Patients with statin discontinuation were younger, had lower body mass index (BMI), included a higher number of smokers and drinkers, did not exercise regularly, with fewer cases of hypertension and diabetes mellitus than those without statin discontinuation (<i>p</i><0.001). Compared with patients aged 20-29 years, the risk of statin discontinuation showed a U-shaped relationship with age (odds ratios [ORs]: 0.619 in 30-39 years; 0.454 in 40-49 years; 0.345 in 50-59 years; 0.307 in 60-69 years; 0.324 in 70-79 years; and 0.415 in ≥80 years). In addition, increased BMI was associated with decreased risk of statin discontinuation (ORs: 0.969 with 25.0-29.9 kg/m², and 0.890 with ≥30.0 kg/m²). Patients with hypertension and diabetes mellitus were at a lower risk of statin discontinuation (OR: 0.414 for hypertension; 0.416 for diabetes mellitus).</p><p><strong>Conclusion: </strong>The prevalence of patients with statin discontinuation in Korea was 39.44% at 1 to 2 years after initial statin treatment.</p>","PeriodicalId":16284,"journal":{"name":"Journal of Lipid and Atherosclerosis","volume":"13 1","pages":"41-52"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10825567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scavenger Receptor BI Deficiency in Mice Is Associated With Plasma Ceramide and Sphingomyelin Accumulation and a Reduced Cholesteryl Ester Fatty Acid Length and Unsaturation Degree.","authors":"Menno Hoekstra, Zhengzheng Zhang, Peter W Lindenburg, Miranda Van Eck","doi":"10.12997/jla.2024.13.1.69","DOIUrl":"10.12997/jla.2024.13.1.69","url":null,"abstract":"<p><strong>Objective: </strong>Scavenger receptor class B type I (SR-BI) is primarily known for its role in the selective uptake of cholesteryl esters (CEs) from high-density lipoproteins (HDLs). Here we investigated whether SR-BI deficiency is associated with other potentially relevant changes in the plasma lipidome than the established effect of HDL-cholesterol elevation.</p><p><strong>Methods: </strong>Targeted ultra-high-performance liquid chromatography-tandem mass spectrometry was utilized to measure lipid species in plasma from female wild-type and SR-BI knockout mice.</p><p><strong>Results: </strong>SR-BI deficiency was associated with a reduction in the average CE fatty acid length (-2%; <i>p</i><0.001) and degree of CE fatty acid unsaturation (-18%; <i>p</i><0.001) due to a relative shift from longer, polyunsaturated CE species CE (20:4), CE (20:5), and CE (22:6) towards the mono-unsaturated CE (18:1) species. Sphingomyelin (SM) levels were 64% higher (<i>p</i><0.001) in SR-BI knockout mice without a parallel change in (lyso)phosphatidylcholine (LPC) concentrations, resulting in an increase in the SM/LPC ratio from 0.102±0.005 to 0.163±0.003 (<i>p</i><0.001). In addition, lower LPC lengths (-5%; <i>p</i><0.05) and fatty acid unsaturation degrees (-20%; <i>p</i><0.01) were detected in SR-BI knockout mice. Furthermore, SR-BI deficiency was associated with a 4.7-fold increase (<i>p</i><0.001) in total plasma ceramide (Cer) levels, with a marked >9-fold rise (<i>p</i><0.001) in Cer (d18:1/24:1) concentrations.</p><p><strong>Conclusion: </strong>We have shown that SR-BI deficiency in mice not only impacts the CE concentrations, length, and saturation index within the plasma compartment, but is also associated with plasma accumulation of several Cer and SM species that may contribute to the development of specific hematological and metabolic (disease) phenotypes previously detected in SR-BI knockout mice.</p>","PeriodicalId":16284,"journal":{"name":"Journal of Lipid and Atherosclerosis","volume":"13 1","pages":"69-79"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10825577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of the Wnt Pathways as a Potential Target Pathway in Atherosclerosis.","authors":"Anastasia V Poznyak,&nbsp;Vasily N Sukhorukov,&nbsp;Mikhail A Popov,&nbsp;Yegor S Chegodaev,&nbsp;Anton Y Postnov,&nbsp;Alexander N Orekhov","doi":"10.12997/jla.2023.12.3.223","DOIUrl":"10.12997/jla.2023.12.3.223","url":null,"abstract":"<p><p>The proteins of the Wnt family are involved in a variety of physiological processes by means of several canonical and noncanonical signaling pathways. Wnt signaling has been recently identified as a major player in atherogenesis. In this review, we summarize the existing knowledge on the influence of various components of the Wnt signaling pathways on the initiation and progression of atherosclerosis and associated conditions. We used the PubMed database to search for recent papers on the involvement of the Wnt pathways in atherosclerosis. We used the combination of \"Wnt\" and \"atherosclerosis\" keywords to find the initial papers, and chose papers published after 2018. In the first section of the paper, we describe the general mechanisms of the Wnt signaling pathways and their components. The next section is dedicated to existing studies assessing the implication of Wnt signaling elements in different atherogenic processes, such as cholesterol retention, endothelial dysfunction, vascular inflammation, and atherosclerotic calcification of the vessels. Lastly, various therapeutic strategies based on interference with the Wnt signaling pathways are considered. We also compare the efficacy and availability of the proposed treatment methods. Wnt signaling can be considered a potential target in the treatment and prevention of atherosclerosis. Therefore, in this review, we reviewed evidences showing that wnt signaling is an important signal for developing appropriate treatment strategies for atherosclerosis.</p>","PeriodicalId":16284,"journal":{"name":"Journal of Lipid and Atherosclerosis","volume":"12 3","pages":"223-236"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/91/96/jla-12-223.PMC10548192.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41133506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Cardiovascular Effect of Tirzepatide: A Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide Dual Agonist.","authors":"Yun Kyung Cho,&nbsp;Yoo La Lee,&nbsp;Chang Hee Jung","doi":"10.12997/jla.2023.12.3.213","DOIUrl":"10.12997/jla.2023.12.3.213","url":null,"abstract":"Glucagon-like peptide-1 (GLP-1) receptor agonists have been used extensively in the clinic and have an established safety profile in cardiovascular disease settings. For the treatment of peptide-secreting enteroendocrine cells, most research has focused on developing peptide multi-agonists as most of these cells are multihormonal. Among the various peptides secreted by enteroendocrine cells, the combination of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) is an attractive strategy for treating type 2 diabetes mellitus (T2DM) because both of these hormones have glucose-lowering actions. Tirzepatide, a synthetic peptide composed of 39 amino acids, functions as a dual receptor agonist of both the GIP and GLP-1 receptors. This unique mechanism of action has earned tirzepatide the nickname “twincretin.” Tirzepatide’s dual agonist activity may be the mechanism by which tirzepatide significantly reduces glycated hemoglobin levels and body weight in patients with T2DM as observed in phase 3 clinical trials. Besides its glucose-lowering and anti-obesity effects, tirzepatide has been reported to have potential cardiovascular benefits. In this review, we discuss the cardiovascular effects of tirzepatide based on the available preclinical and clinical data.","PeriodicalId":16284,"journal":{"name":"Journal of Lipid and Atherosclerosis","volume":"12 3","pages":"213-222"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a6/ae/jla-12-213.PMC10548186.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41117196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vegetarian Diet for Cardiovascular Disease Risk Reduction: Cons.","authors":"Sung Nim Han","doi":"10.12997/jla.2023.12.3.323","DOIUrl":"10.12997/jla.2023.12.3.323","url":null,"abstract":"<p><p>Numerous studies have reported that adopting a plant-based diet can significantly reduce the risk of cardiovascular diseases (CVDs). Not only does a vegetarian diet help mitigate the risk of these diseases, but it also contributes to enhancing environmental sustainability. However, it is not necessary to universally recommend a vegetarian diet as a preventive measure against CVDs. More research is needed to determine whether completely excluding animal products is necessary, or if adhering to a predominantly plant-based diet is sufficient. In this opinion paper, the potential adverse health effects of a vegetarian diet and the barriers associated with adopting it will be discussed, in order to provide a rationale for the disadvantages of using a vegetarian diet for CVD risk reduction.</p>","PeriodicalId":16284,"journal":{"name":"Journal of Lipid and Atherosclerosis","volume":"12 3","pages":"323-328"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/95/59/jla-12-323.PMC10548188.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41163688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the Practical Differences in LDL-C Estimates Calculated by Friedewald, Martin/Hopkins, or NIH Equation 2: An Observation Cross-Sectional Study.","authors":"Inga Wang,&nbsp;Mohammad H Rahman,&nbsp;Stephen Hou,&nbsp;Hui-Wen Lin","doi":"10.12997/jla.2023.12.3.252","DOIUrl":"10.12997/jla.2023.12.3.252","url":null,"abstract":"<p><strong>Objective: </strong>Low-density lipoprotein-cholesterol (LDL-C) remains a clinically important cholesterol target in primary prevention of atherosclerotic cardiovascular disease. The present study aimed to assess the practical differences among three equations utilized for the estimation of LDL-C: the Friedewald, the Martin/Hopkins, and the NIH equation 2.</p><p><strong>Methods: </strong>Blood lipid measurements from 4,556 noninstitutionalized participants, aged 12 to 80, were obtained from the 2017-2020 National Health and Nutrition Examination Survey study. We 1) assessed the differences between three calculated LDL-C estimates, 2) examined the correlations between LDL-C estimates using correlation coefficients and regression, and 3) investigated the degree of agreement in classifying individuals into the LDL-C category using weighted Kappa and percentage of agreement.</p><p><strong>Results: </strong>The differences in LDL-C estimates between equations varied by sex and triglyceride levels (<i>p</i><0.001). Overall, the mean of absolute differences between Friedewald and Martin/Hopkins was 3.17 mg/dL (median=2.0, 95% confidence interval [CI] [3.07-3.27]). The mean of absolute differences between Friedewald and NIH Equation 2 was 2.08 mg/dL (median=2.0, 95% CI [2.03-2.14]). Friedewald correlated highly with Martin/Hopkins (r=0.991, rho=0.989) and NIH Equation 2 (r=0.998, rho=0.997). Cohen's weighted Kappa=0.92 between Friedewald and Martin/Hopkins, and 0.95 between Friedewald and NIH equation 2. The percentage of agreement in classifying individuals into the same LDL-C category was 93.0% between Friedewald and Martin/Hopkins, and 95.4% between Friedewald and NIH equation 2.</p><p><strong>Conclusion: </strong>Understanding the practical differences in LDL-C calculations can be helpful in facilitating decision-making during a paradigm shift.</p>","PeriodicalId":16284,"journal":{"name":"Journal of Lipid and Atherosclerosis","volume":"12 3","pages":"252-266"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f9/8a/jla-12-252.PMC10548185.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41135733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid-Lowering Efficacy of Combination Therapy With Moderate-Intensity Statin and Ezetimibe Versus High-Intensity Statin Monotherapy: A Randomized, Open-Label, Non-Inferiority Trial From Korea.","authors":"Hyejung Choi, Si-Hyuck Kang, Sang-Woo Jeong, Chang-Hwan Yoon, Tae-Jin Youn, Woo Hyuk Song, Dong Woon Jeon, Sang Wook Lim, Jun-Hee Lee, Seong-Wook Cho, In-Ho Chae, Cheol-Ho Kim","doi":"10.12997/jla.2023.12.3.277","DOIUrl":"10.12997/jla.2023.12.3.277","url":null,"abstract":"<p><strong>Objective: </strong>This phase IV, multicenter, randomized controlled, open-label, and parallel clinical trial aimed to compare the efficacy and safety of ezetimibe and moderate intensity rosuvastatin combination therapy to that of high intensity rosuvastatin monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD).</p><p><strong>Methods: </strong>This study enrolled patients with ASCVD and after a four-week screening period, patients were randomly assigned to receive either rosuvastatin and ezetimibe (RE 10/10 group) or high-intensity rosuvastatin (R20 group) only in a 1:1 ratio. The primary outcome was the difference in the percent change in the mean low-density lipoprotein cholesterol (LDL-C) level from baseline to 12 weeks between two groups after treatment.</p><p><strong>Results: </strong>The study found that after 12 and 24 weeks of treatment, the RE10/10 group had a greater reduction in LDL-C level compared to the R20 group (-22.9±2.6% vs. -15.6 ± 2.5% [<i>p</i>=0.041] and -24.2±2.5% vs. -12.9±2.4% [<i>p</i>=0.001] at 12 and 24 weeks, respectively). Moreover, a greater number of patients achieved the target LDL-C level of ≤70 mg/dL after the treatment period in the combination group (74.6% vs. 59.9% [<i>p</i>=0.012] and 76.2% vs. 50.8% [<i>p</i><0.001] at 12 and 24 weeks, respectively). Importantly, there were no significant differences in the occurrence of overall adverse events and adverse drug reactions between two groups.</p><p><strong>Conclusion: </strong>Moderate-intensity rosuvastatin and ezetimibe combination therapy had better efficacy in lowering LDL-C levels without increasing adverse effects in patients with ASCVD than high-intensity rosuvastatin monotherapy.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT03494270.</p>","PeriodicalId":16284,"journal":{"name":"Journal of Lipid and Atherosclerosis","volume":"12 3","pages":"277-289"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/db/7b/jla-12-277.PMC10548190.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41128255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Public Awareness of Dyslipidemia Among the Korean Population: A Survey Study.","authors":"Jae Hyun Bae, Eun-Sun Jin, Sung Eun Kim, Shinae Kang, Jong-Young Lee, Minsu Kim, Heung Yong Jin, Min-Jeong Shin, In-Kyung Jeong","doi":"10.12997/jla.2023.12.3.307","DOIUrl":"10.12997/jla.2023.12.3.307","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to assess the level of public awareness regarding dyslipidemia and its management among the Korean population.</p><p><strong>Methods: </strong>We conducted a web- or mobile-based survey study targeting the general population, using various recruitment methods, between July 25, 2022 and August 26, 2022. The questionnaire consisted of 12 questions designed to collect demographic information and evaluate participants' awareness and knowledge about dyslipidemia.</p><p><strong>Results: </strong>In total, 2,882 participants who completed the survey were included in the analysis. Among the participants, a substantial majority (89.1%) were familiar with the concepts of \"good cholesterol\" and \"bad cholesterol,\" while a comparatively lower percentage (just 46.7%) were acquainted with the term \"dyslipidemia.\" Noticeable variations in understanding were observed when examining specific aspects of dyslipidemia management, including diet, exercise, and pharmacotherapy.</p><p><strong>Conclusion: </strong>The results of this survey underscore the significance of enhancing public awareness about dyslipidemia within the context of health literacy, demonstrating the necessity for a more comprehensive approach that includes education and policymaking to effectively manage dyslipidemia.</p>","PeriodicalId":16284,"journal":{"name":"Journal of Lipid and Atherosclerosis","volume":"12 3","pages":"307-314"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fa/3c/jla-12-307.PMC10548193.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41135644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated Lipoprotein(a) Levels and Atrial Fibrillation: A Systematic Review.","authors":"Walter Masson,&nbsp;Leandro Barbagelata,&nbsp;Juan P Nogueira,&nbsp;Pablo Corral,&nbsp;Augusto Lavalle-Cobo,&nbsp;Francisco J Romeo","doi":"10.12997/jla.2023.12.3.267","DOIUrl":"10.12997/jla.2023.12.3.267","url":null,"abstract":"<p><strong>Objective: </strong>The role of lipoprotein(a) (Lp[a]) as a possibly causal risk factor for atherosclerotic cardiovascular disease has been well established. However, the clinical evidence regarding the association between Lp(a) levels and atrial fibrillation (AF) remains limited and inconsistent. This study aimed to analyze the association between elevated Lp(a) levels or single-nucleotide polymorphisms (SNPs) related to high levels of Lp(a) and AF.</p><p><strong>Methods: </strong>This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A literature search was performed to identify studies that evaluated the association between Lp(a) levels or SNPs related to high levels of Lp(a) and AF. Observational studies with a cross-sectional, case-control, or cohort design were included in this systematic review, without limitations according to language, country, or publication type.</p><p><strong>Results: </strong>Eleven observational studies including 1,246,817 patients were eligible for this systematic review. Two cross-sectional studies, 5 prospective/retrospective cohort studies, and 4 Mendelian randomization studies were analyzed. Two cross-sectional studies that compared Lp(a) levels between patients with and without AF showed conflicting results. Cohort studies that evaluated the incidence of AF according to Lp(a) levels showed different results: no association (3 studies), a positive association (1 study), and an inverse relationship (1 study). Finally, Mendelian randomization studies also showed heterogeneous results (positive association: 2 studies; inverse association: 1 study; no association: 1 study).</p><p><strong>Conclusion: </strong>Although there could be an association between Lp(a) levels and AF, the results of the studies published to date are contradictory and not yet definitive. Therefore, further research should clarify this issue.</p>","PeriodicalId":16284,"journal":{"name":"Journal of Lipid and Atherosclerosis","volume":"12 3","pages":"267-276"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c7/9b/jla-12-267.PMC10548189.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41119765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin Reduces the Progression of Atherogenesis by Regulating the Sestrin2-mTOR Pathway in Obese and Diabetic Rats.","authors":"Saravanakumar Sundararajan,&nbsp;Isaivani Jayachandran,&nbsp;Gautam Kumar Pandey,&nbsp;Saravanakumar Venkatesan,&nbsp;Anusha Rajagopal,&nbsp;Kuppan Gokulakrishnan,&nbsp;Muthuswamy Balasubramanyam,&nbsp;Viswanathan Mohan,&nbsp;Nagaraj Manickam","doi":"10.12997/jla.2023.12.3.290","DOIUrl":"10.12997/jla.2023.12.3.290","url":null,"abstract":"<p><strong>Objective: </strong>In previous research, we found that Sestrin2 has a strong association with plasma atherogenicity and combats the progression of atherogenesis by regulating the AMPK-mTOR pathway. Metformin, an activator of AMPK, is widely used as a first-line therapy for diabetes, but its role in preventing atherosclerosis and cardiac outcomes is unclear. Hence, we aimed to assess the effect of metformin on preventing atherosclerosis and its regulatory role in the Sestrin2-AMPK -mTOR pathway in obese/diabetic rats.</p><p><strong>Methods: </strong>Animals were fed a high-fat diet to induce obesity, administered streptozotocin to induce diabetes, and then treated with metformin (150 mg/kg body weight) for 14 weeks. Aorta and heart tissues were analyzed for Sestrin2 status by western blotting and immunohistochemistry, AMPK and mTOR activities were investigated using western blotting, and atherogenicity-related events were evaluated using reverse transcription quantitative polymerase chain reaction and histology.</p><p><strong>Results: </strong>Obese and diabetic rats showed significant decrease in Sestrin2 levels and AMPK activity, accompanied by increased mTOR activity in the heart and aorta tissues. Metformin treatment significantly restored Sestrin2 and AMPK levels, reduced mTOR activity, and restored the altered expression of inflammatory markers and adhesion molecules in obese and diabetic rats to normal levels. A histological analysis of samples from obese and diabetic rats showed atherosclerotic lesions both in aorta and heart tissues. The metformin-treated rats showed a decrease in atherosclerotic lesions, cardiac hypertrophy, and cardiomyocyte degeneration.</p><p><strong>Conclusion: </strong>This study presents further insights into the beneficial effects of metformin and its protective role against atherosclerosis through regulation of the Sestrin2-AMPK-mTOR pathway.</p>","PeriodicalId":16284,"journal":{"name":"Journal of Lipid and Atherosclerosis","volume":"12 3","pages":"290-306"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/20/b6/jla-12-290.PMC10548184.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41128098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}