Atherosclerosis最新文献

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Homozygous familial hypercholesterolemia evaluation and survival single center study in Saudi Arabia: The HESSA registry 沙特阿拉伯纯合子家族性高胆固醇血症评估和生存单中心研究:HESSA登记
IF 4.9 2区 医学
Atherosclerosis Pub Date : 2025-05-02 DOI: 10.1016/j.atherosclerosis.2025.119214
Naji Kholaif , Lin Batha , Sumayah Aljenedil , Zuhier Ahmed Awan , Nadiah AlRuwaili , Abdulrahman Khalid Habib , Ahmed Awni Jouda , Maria Teresa Savo , Fadl Elmula M. Fadl Elmula , Tahir I. Mohamed , Abdullah Al-Ashwal , Valeria Pergola , Naser Elkum , Domenico Galzerano
{"title":"Homozygous familial hypercholesterolemia evaluation and survival single center study in Saudi Arabia: The HESSA registry","authors":"Naji Kholaif ,&nbsp;Lin Batha ,&nbsp;Sumayah Aljenedil ,&nbsp;Zuhier Ahmed Awan ,&nbsp;Nadiah AlRuwaili ,&nbsp;Abdulrahman Khalid Habib ,&nbsp;Ahmed Awni Jouda ,&nbsp;Maria Teresa Savo ,&nbsp;Fadl Elmula M. Fadl Elmula ,&nbsp;Tahir I. Mohamed ,&nbsp;Abdullah Al-Ashwal ,&nbsp;Valeria Pergola ,&nbsp;Naser Elkum ,&nbsp;Domenico Galzerano","doi":"10.1016/j.atherosclerosis.2025.119214","DOIUrl":"10.1016/j.atherosclerosis.2025.119214","url":null,"abstract":"<div><h3>Background and aims background</h3><div>Homozygous Familial Hypercholesterolemia (HoFH) is a rare, life-threatening genetic disorder causing extremely high low density lipoprotein cholesterol (LDL-C) levels, leading to early cardiovascular disease (CVD) and premature death. In Saudi Arabia, where consanguinity is common, HoFH prevalence is higher with unique genetic pathogenic familial hypercholesterolemia (FH) causing variants and treatment challenges. This study aims to analyze the clinical, genetic, treatment, and cardiovascular outcomes data of Saudi pediatric and adult HoFH patients treated at King Faisal Specialist Hospital &amp; Research Centre (KFSHRC) over 23 years.</div></div><div><h3>Methods</h3><div>A retrospective review of all patients (LDL-C &gt;8 mmol/L) at KFSHRC (2000–2023) using European Atherosclerosis Society 2023 criteria to confirm HoFH. Data from those confirmed included demographics, lipid profiles, pathogenic FH-causing variants, treatments, mortality, and cardiovascular outcomes.</div></div><div><h3>Results</h3><div>Among 514 severe hypercholesterolemia cases, 127 had HoFH. Diagnosis occurred at an average age of 14.3 ± 9.7 years. The mortality was 16 %, and 12 % were lost to follow-up. Cardiovascular interventions were performed in 31 % (coronary interventions in 28 % and aortic valve replacement in 17 %). The most common pathogenic FH-causing variants (57 %) was the founder null mutation c.2027del p.(Gly676Alafs∗33). Statins and ezetimibe were the primary treatments (73 %), but many required LDL-apheresis (36 %) or liver transplantation (LTx) (21 %). The peri-operative mortality for LTx was 7 %, but there was no long-term mortality on average follow-up of 6.2 ± 3.6 years, with only one patient requiring percutaneous coronary intervention. Adults were more likely to receive statins/ezetimibe (94 %/91 % vs. 50 %/53 % in pediatrics, p &lt; 0.01) and LDL-apheresis (64 % vs. 8 %, p &lt; 0.001), while liver transplantation was more common in children (38 % vs. 7 %, p &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>This study highlights the burden of null LDL-R pathogenic FH-causing variants and the frequent need for invasive treatments in Saudi HoFH patients. Liver transplantation is a viable option with low peri-operative mortality and favorable long-term disease-free survival. Early diagnosis, regional genetic screening, and access to advanced therapies are essential in achieving better outcomes.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"405 ","pages":"Article 119214"},"PeriodicalIF":4.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
BAM15 inhibits endothelial pyroptosis via the NLRP3/ASC/caspase-1 pathway to alleviate atherosclerosis BAM15通过NLRP3/ASC/caspase-1途径抑制内皮细胞焦亡,缓解动脉粥样硬化
IF 4.9 2区 医学
Atherosclerosis Pub Date : 2025-05-01 DOI: 10.1016/j.atherosclerosis.2025.119226
Su Zhong , Hui Shen , Xiaoman Dai , Lianming Liao , Chun Huang
{"title":"BAM15 inhibits endothelial pyroptosis via the NLRP3/ASC/caspase-1 pathway to alleviate atherosclerosis","authors":"Su Zhong ,&nbsp;Hui Shen ,&nbsp;Xiaoman Dai ,&nbsp;Lianming Liao ,&nbsp;Chun Huang","doi":"10.1016/j.atherosclerosis.2025.119226","DOIUrl":"10.1016/j.atherosclerosis.2025.119226","url":null,"abstract":"<div><h3>Background and aims</h3><div>Atherosclerosis (AS) is a chronic inflammatory disease contributing to major cardiovascular events. This study aimed to investigate the effects of BAM15, a mitochondrial uncoupler, on regulating the NLRP3/ASC/caspase-1 signaling pathway to suppress endothelial cell pyroptosis and mitigate AS.</div></div><div><h3>Methods</h3><div>AS was induced in ApoE−/− mice through a high-fat diet (HFD), and the therapeutic effects of BAM15 (5 mg/kg/day, s. c.) were evaluated. Histological analyses, including HE staining and oil red O staining, were used to assess aortic pathology and lipid deposition. Serum inflammatory cytokines (IL-1β, IL-18) were quantified by ELISA. Mouse primary aortic endothelial cells (MAECs) were treated with oxidized low-density lipoprotein (ox-LDL) to simulate AS condition <em>in vitro</em>. Mitochondrial reactive oxygen species (mtROS) expression and oxidized (ox)-mtDNA content were detected by Mitosox staining and ELISA, respectively. Western blot was used to assess the expression of pyroptosis-related proteins, including GSDMD-NT, NLRP3, ASC, and cleaved-caspase-1.</div></div><div><h3>Results</h3><div>BAM15 reduced atherosclerotic plaque formation, lipid deposition, and inflammation, and diminished mtROS expression and ox-mtDNA content in the AS mouse models. In both <em>in vivo</em> and <em>in vitro</em> experiments, BAM15 markedly inhibited the activation of the NLRP3 inflammasome, leading to reduced pyroptosis in endothelial cells. Activation of the NLRP3/ASC/caspase-1 signaling pathway by Nigericin partially reversed the protective effects of BAM15, underscoring the pivotal role of NLRP3 inflammasome inhibition in endothelial pyroptosis suppression.</div></div><div><h3>Conclusions</h3><div>BAM15 effectively inhibits endothelial cell pyroptosis by reducing mtROS production and ox-mtDNA release to suppress the NLRP3/ASC/caspase-1 signaling pathway, thereby alleviating AS in both <em>in vivo</em> and <em>in vitro</em> models.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"406 ","pages":"Article 119226"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
KUS121, a novel VCP modulator, attenuates atherosclerosis development by reducing ER stress and inhibiting glycolysis through the maintenance of ATP levels in endothelial cells KUS121是一种新型的VCP调节剂,通过维持内皮细胞的ATP水平来减少内质网应激和抑制糖酵解,从而减缓动脉粥样硬化的发展
IF 4.9 2区 医学
Atherosclerosis Pub Date : 2025-05-01 DOI: 10.1016/j.atherosclerosis.2025.119223
Fuquan Zou , Osamu Baba , Takahiro Horie , Yasuhiro Nakashima , Shuhei Tsuji , Tomohiro Yamasaki , Chiharu Otani , Sijia Xu , Miyako Imanaka , Kazuki Matsushita , Keita Suzuki , Eitaro Kume , Hidenori Kojima , Qiuxian Qian , Kayo Kimura , Naoya Sowa , Akira Kakizuka , Koh Ono
{"title":"KUS121, a novel VCP modulator, attenuates atherosclerosis development by reducing ER stress and inhibiting glycolysis through the maintenance of ATP levels in endothelial cells","authors":"Fuquan Zou ,&nbsp;Osamu Baba ,&nbsp;Takahiro Horie ,&nbsp;Yasuhiro Nakashima ,&nbsp;Shuhei Tsuji ,&nbsp;Tomohiro Yamasaki ,&nbsp;Chiharu Otani ,&nbsp;Sijia Xu ,&nbsp;Miyako Imanaka ,&nbsp;Kazuki Matsushita ,&nbsp;Keita Suzuki ,&nbsp;Eitaro Kume ,&nbsp;Hidenori Kojima ,&nbsp;Qiuxian Qian ,&nbsp;Kayo Kimura ,&nbsp;Naoya Sowa ,&nbsp;Akira Kakizuka ,&nbsp;Koh Ono","doi":"10.1016/j.atherosclerosis.2025.119223","DOIUrl":"10.1016/j.atherosclerosis.2025.119223","url":null,"abstract":"<div><h3>Background and aims</h3><div>Endoplasmic reticulum (ER) stress pathways contribute to atherosclerosis progression. Recently, we developed Kyoto University Substance (KUS) 121, which selectively inhibits ATPase activities of valosin-containing protein (VCP), consequently conserving intracellular ATP consumption and mitigating ER stress. This study evaluated the efficacy of KUS121 in atherosclerosis.</div></div><div><h3>Methods and results</h3><div>KUS121 was administered daily to <em>Apoe</em><sup><em>−/−</em></sup> mice fed a Western diet (WD) for 8 weeks. KUS121 treatment resulted in a 40–50 % reduction in atherosclerosis progression. Interestingly, we observed that C/EBP homologous protein (Chop), a well-established ER stress marker, was predominantly expressed in plaque endothelium. In human EA.hy926 endothelial cells, KUS121 prevented ER stress-induced apoptosis and downregulated the Inositol-requiring enzyme 1 alpha (IRE1α)-associated inflammatory pathways. Consistent with these <em>in vitro</em> findings, KUS121 treatment significantly reduced endothelial apoptosis, as shown by TUNEL and cleaved caspase-3 staining, and inflammation, as demonstrated by immunostaining of Nuclear factor kappa B (NF-κB) and Intercellular adhesion molecule (Icam) 1 at plaque endothelium. We also demonstrated that KUS121 maintained ATP levels in EA.hy926 cells and atherosclerotic plaque lesions using single-wavelength and the FRET-based fluorescent ATP sensors. Supplementation of intracellular ATP by methyl pyruvate attenuated ER stress-induced apoptotic and inflammatory pathways in endothelial cells, similar to KUS121. Besides affecting ER stress, KUS121 also reduced inflammation even without ER stress by inhibiting glycolysis through increased intracellular ATP levels in LPS-treated EA.hy926 cells.</div></div><div><h3>Conclusions</h3><div>KUS121 can be a new therapeutic option for atherosclerotic diseases by maintaining intracellular ATP levels, leading to the attenuation of ER stress and glycolysis in plaque endothelium.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"405 ","pages":"Article 119223"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to “Familial chylomicronemia syndrome and treatments to target hepatic APOC3 mRNA” [Atherosclerosis (2025) 403 119114] “家族性乳糜微粒血症综合征及针对肝脏APOC3 mRNA的治疗”[动脉粥样硬化(2025)403 119114]的勘误表
IF 4.9 2区 医学
Atherosclerosis Pub Date : 2025-05-01 DOI: 10.1016/j.atherosclerosis.2025.119210
Eliot A. Brinton , Robert H. Eckel , Daniel Gaudet , Christie M. Ballantyne , Brenda F. Baker , Henry N. Ginsberg , Joseph L. Witztum
{"title":"Corrigendum to “Familial chylomicronemia syndrome and treatments to target hepatic APOC3 mRNA” [Atherosclerosis (2025) 403 119114]","authors":"Eliot A. Brinton ,&nbsp;Robert H. Eckel ,&nbsp;Daniel Gaudet ,&nbsp;Christie M. Ballantyne ,&nbsp;Brenda F. Baker ,&nbsp;Henry N. Ginsberg ,&nbsp;Joseph L. Witztum","doi":"10.1016/j.atherosclerosis.2025.119210","DOIUrl":"10.1016/j.atherosclerosis.2025.119210","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"405 ","pages":"Article 119210"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Basal and exercise-induced expression of NLRP3 inflammasome-related components is increased in patients with chronic coronary syndrome 慢性冠状动脉综合征患者NLRP3炎性小体相关成分的基础表达和运动诱导表达增加
IF 4.9 2区 医学
Atherosclerosis Pub Date : 2025-04-30 DOI: 10.1016/j.atherosclerosis.2025.119227
Zeid Mahmood , Maria Bäck , Per Leanderson , Rebecka Thune , Camilla Skoglund , Lena Jonasson
{"title":"Basal and exercise-induced expression of NLRP3 inflammasome-related components is increased in patients with chronic coronary syndrome","authors":"Zeid Mahmood ,&nbsp;Maria Bäck ,&nbsp;Per Leanderson ,&nbsp;Rebecka Thune ,&nbsp;Camilla Skoglund ,&nbsp;Lena Jonasson","doi":"10.1016/j.atherosclerosis.2025.119227","DOIUrl":"10.1016/j.atherosclerosis.2025.119227","url":null,"abstract":"<div><h3>Background and aims</h3><div>NLRP3 inflammasome is considered a critical actor in the inflammatory process of coronary artery disease. Increased expression of NLRP3 inflammasome components has been reported in patients with acute coronary syndrome, but whether this persists beyond the acute phase is less known. We performed a prospective study to investigate whether basal and/or exercise-induced NLRP3 inflammasome components were elevated in patients with chronic coronary syndrome (CCS).</div></div><div><h3>Methods</h3><div>Patients (n = 81) underwent exercise stress tests twice: 3–4 weeks and 3–6 months after a major coronary event, whereas controls (n = 30) performed it once. Concentrations of interleukin(IL)-18, IL-1Ra and IL-6 were measured before and 30 min after exercise. Genes related to NLRP3 inflammasome and NFκB signaling pathways were measured in blood mononuclear cells before and after exercise. On the first visit, patients were prescribed an exercise-based cardiac rehabilitation program. Physical activity levels were reported on both visits.</div></div><div><h3>Results</h3><div>Patients were clinically stable and exhibited increased exercise capacity as well as increased self-reported physical activity between visits. Basal plasma levels of IL-18, as well as exercise-induced levels of IL-18 and IL-1Ra, were higher in patients compared with controls on both visits. Also, basal gene expression of <em>NLRP3</em> was higher in patients, as were several NFκB-related genes. After exercise, gene expression related to NLRP3 inflammasome activation, in particular <em>P2RX7</em>, was higher in patients on both visits.</div></div><div><h3>Conclusions</h3><div>Up to 6 months after a coronary event, patients exhibited an increase in NLRP3 inflammasome-related components that was even more pronounced after acute exercise, compared with controls. The results indicate that a primed NLRP3 inflammasome system is maintained despite clinical stability and best available therapy, highlighting the need to further combat inflammation in patients with CCS<strong>.</strong></div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"405 ","pages":"Article 119227"},"PeriodicalIF":4.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cardiovascular risk posed by the exposome 暴露者造成的心血管风险
IF 4.9 2区 医学
Atherosclerosis Pub Date : 2025-04-30 DOI: 10.1016/j.atherosclerosis.2025.119222
Andreas Daiber , Sanjay Rajagopalan , Marin Kuntic , Thomas Münzel
{"title":"Cardiovascular risk posed by the exposome","authors":"Andreas Daiber ,&nbsp;Sanjay Rajagopalan ,&nbsp;Marin Kuntic ,&nbsp;Thomas Münzel","doi":"10.1016/j.atherosclerosis.2025.119222","DOIUrl":"10.1016/j.atherosclerosis.2025.119222","url":null,"abstract":"<div><div>Chronic non-communicable diseases (NCDs) account for 2/3 of global deaths annually, primarily due to an aging population and external risk factors such as air/water/soil pollution, traffic noise, mental stress, and climate change emanating from the environment. These factors contribute to premature deaths and loss of healthy life years, as reflected by disability-adjusted life years. The exposome concept was proposed 16 years ago as a new research field to investigate environment-health associations, also by considering the underlying pathophysiological pathways. The exposome describes lifelong environmental exposures, besides pollutants also socioeconomic and lifestyle factors, aiming to explain the associated diseases and deaths. The exposome can be divided into the specific and general external environment and further subcategories such as organ-specific exposomes as well as spatially and temporally restricted pollutomes. The exposome also shows considerable interaction with genetic predisposition and pre-established chronic diseases, characteristics of the vulnerable groups. The present overview provides background information on the impact of the environment on health and disease by considering recent data of the Global Burden of Disease Study. We also explain the exposome concept with the help of selected studies, briefly describe how the exposome is measured, and discuss biomarkers identified by exposomic research and their impact on the development and progression of atherosclerosis. Major pathophysiological pathways comprise exacerbated stress hormone signaling, oxidative stress, inflammation and circadian rhythm dysregulation promoting impairment of cardiometabolic function. The present overview highlights the relevance of the exposome for future health research and preventive medicine, especially concerning cardiovascular diseases and therapy.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"405 ","pages":"Article 119222"},"PeriodicalIF":4.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Increased intestinal mucosal permeability and metabolic endotoxemia predict the risk of cardiovascular mortality 肠粘膜通透性增加和代谢性内毒素血症可预测心血管死亡风险
IF 4.9 2区 医学
Atherosclerosis Pub Date : 2025-04-26 DOI: 10.1016/j.atherosclerosis.2025.119220
J. Parantainen , G. Barreto , T.E. Strandberg , N. Mars , K. Nurmi , K.K. Eklund
{"title":"Increased intestinal mucosal permeability and metabolic endotoxemia predict the risk of cardiovascular mortality","authors":"J. Parantainen ,&nbsp;G. Barreto ,&nbsp;T.E. Strandberg ,&nbsp;N. Mars ,&nbsp;K. Nurmi ,&nbsp;K.K. Eklund","doi":"10.1016/j.atherosclerosis.2025.119220","DOIUrl":"10.1016/j.atherosclerosis.2025.119220","url":null,"abstract":"<div><h3>Background and aims</h3><div>Low-grade chronic inflammation is a pathogenetic factor in atherosclerotic cardiovascular diseases (ASCVD), but the underlying mechanisms are not well understood. We aimed to explore the role of intestinal permeability and ensuing metabolic endotoxemia as risk factors for cardiovascular mortality.</div></div><div><h3>Methods</h3><div>A random sub-cohort of home-living participants from the Helsinki Businessmen Study (HBS), born between 1919 and 1934 and followed since 1964, was recalled in 2003 (n = 632), 2011 (n = 316) and 2017 (n = 82). Six biomarkers representing intestinal permeability and endotoxemia were measured and the results were combined with extensive data on ASCVD prevalence, conventional risk factors, and mortality.</div></div><div><h3>Results</h3><div>Correlation on the individual levels was observed for zonulin, lipopolysaccharide-binding protein (LBP), and intestinal fatty acid-binding protein (I-FABP) across the entire 15-year follow-up. These biomarkers are highly intercorrelated. Particularly zonulin, a marker of intestinal permeability, correlated with most of the conventional ASCVD risk factors. None of the biomarkers correlated with prevalent ASCVD, but higher levels of zonulin and LBP associated with 10-year risk of death from coronary artery disease (CAD, age-adjusted <em>p</em> &lt; 0.001 and <em>p</em> = 0.006, respectively).</div></div><div><h3>Conclusions</h3><div>The results support metabolic endotoxemia as a contributing pathogenetic factor in atherosclerotic cardiovascular disease with an adverse outcome. Of the surrogate biomarkers studied, zonulin was the most robust predictor of mortality in CAD. Levels of zonulin, LBP, and I-FABP remained relatively stable in individuals over the 15-year follow up, suggesting a potential role for them as biomarkers for ASCVD risk.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"405 ","pages":"Article 119220"},"PeriodicalIF":4.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Valine acts as an early biomarker and exacerbates pathological cardiac hypertrophy by impairing mitochondrial quality control 缬氨酸作为早期生物标志物,通过损害线粒体质量控制而加剧病理性心肌肥大
IF 4.9 2区 医学
Atherosclerosis Pub Date : 2025-04-26 DOI: 10.1016/j.atherosclerosis.2025.119216
Hongyu Kuang , Dan Li , Yunlin Chen , Hongmi Zou , Fang Li , Zhiyan Gong , Yuxiang Long , Hao Zhou , Huaan Du , Yuehui Yin
{"title":"Valine acts as an early biomarker and exacerbates pathological cardiac hypertrophy by impairing mitochondrial quality control","authors":"Hongyu Kuang ,&nbsp;Dan Li ,&nbsp;Yunlin Chen ,&nbsp;Hongmi Zou ,&nbsp;Fang Li ,&nbsp;Zhiyan Gong ,&nbsp;Yuxiang Long ,&nbsp;Hao Zhou ,&nbsp;Huaan Du ,&nbsp;Yuehui Yin","doi":"10.1016/j.atherosclerosis.2025.119216","DOIUrl":"10.1016/j.atherosclerosis.2025.119216","url":null,"abstract":"<div><h3>Objective</h3><div>Pathological cardiac hypertrophy is an independent risk factor for heart failure (HF). Early identification and timely treatment are crucial for significantly delaying the progression of HF.</div></div><div><h3>Methods</h3><div>Targeted amino acid metabolomics and RNA sequencing (RNA-seq) were combined to explore the underlying mechanism. <em>In vitro</em>, H9c2 cells were stimulated with angiotensin II (Ang II) or were incubated with extra valine after Ang II stimulation. The branched chain alpha-ketoate dehydrogenase kinase (Bckdk) inhibitor 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid (BT2) and rapamycin were utilized to confirm the role of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway in this process.</div></div><div><h3>Results</h3><div>A significant accumulation of valine was detected within hypertrophic hearts from spontaneously hypertensive rats (SHR). When branched chain amino acid (BCAA) degradation was increased by BT2, the most pronounced decrease was observed in the valine level (Δ = 0.185 μmol/g, <em>p</em> &lt; 0.001), and cardiac hypertrophy was ameliorated. The role of imbalanced mitochondrial quality control (MQC), including the suppression of mitophagy and excessive mitochondrial fission, was revealed in myocardial hypertrophy. <em>In vitro</em>, high concentrations of valine exacerbated cardiomyocyte hypertrophy stimulated by Any II, resulting in the accumulation of impaired mitochondria and respiratory chain dysfunction. BT2, rapamycin, and mitochondrial division inhibitor 1 (Mdivi-1) all ameliorated MQC imbalance, mitochondrial damage and oxidative stress in hypertensive models with high valine concentration.</div></div><div><h3>Conclusion</h3><div>Valine exacerbated pathological cardiac hypertrophy by causing a MQC imbalance, probably as an early biomarker for cardiac hypertrophy under chronic hypertension.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"405 ","pages":"Article 119216"},"PeriodicalIF":4.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interleukin-6 modifies Lipoprotein(a) and oxidized phospholipids associated cardiovascular disease risk in a secondary prevention cohort 在二级预防队列中,白细胞介素-6改变脂蛋白(a)和氧化磷脂相关的心血管疾病风险
IF 4.9 2区 医学
Atherosclerosis Pub Date : 2025-04-26 DOI: 10.1016/j.atherosclerosis.2025.119211
Niekbachsh Mohammadnia , Amber van Broekhoven , Willem A. Bax , John W. Eikelboom , Arend Mosterd , Aernoud T.L. Fiolet , Jan G.P. Tijssen , Peter L. Thompson , Dominique P.V. de Kleijn , Sotirios Tsimikas , Jan H. Cornel , Calvin Yeang , Saloua El Messaoudi
{"title":"Interleukin-6 modifies Lipoprotein(a) and oxidized phospholipids associated cardiovascular disease risk in a secondary prevention cohort","authors":"Niekbachsh Mohammadnia ,&nbsp;Amber van Broekhoven ,&nbsp;Willem A. Bax ,&nbsp;John W. Eikelboom ,&nbsp;Arend Mosterd ,&nbsp;Aernoud T.L. Fiolet ,&nbsp;Jan G.P. Tijssen ,&nbsp;Peter L. Thompson ,&nbsp;Dominique P.V. de Kleijn ,&nbsp;Sotirios Tsimikas ,&nbsp;Jan H. Cornel ,&nbsp;Calvin Yeang ,&nbsp;Saloua El Messaoudi","doi":"10.1016/j.atherosclerosis.2025.119211","DOIUrl":"10.1016/j.atherosclerosis.2025.119211","url":null,"abstract":"<div><h3>Background and aims</h3><div>There is a need for effective tools to stratify and modify cardiovascular risk associated with elevated lipoprotein(a) [Lp(a)] and oxidized phospholipids (OxPL). The objective of this analysis was to explore the modifying effects of low-grade inflammation on Lp(a)- and OxPL-associated risk in a secondary prevention cohort.</div></div><div><h3>Methods</h3><div>Levels of Lp(a), OxPL associated with apolipoprotein(a) (OxPL-apo[a]) and apolipoprotein B (OxPL-apoB) were determined in the placebo-arm of the low-dose colchicine 2 trial. Patients were between 35 and 82 years, had established chronic coronary syndrome (CCS), and were clinically stable for at least six months prior to randomization. The outcome was the incidence of the composite endpoint of spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization stratified by biomarker levels using a Cox regression model.</div></div><div><h3>Results</h3><div>There was a significant interaction between Lp(a) and IL-6 &lt;3.2 ng/L (median) and IL-6 ≥3.2 ng/L for the composite endpoint (HR 0.90; 95 %CI 0.78–1.03 vs HR 1.18; 95 %CI 1.01–1.39, P<sub>interaction</sub> = 0.01). No interaction was found for Lp(a) levels in participants with hsCRP &lt;2 mg/L (HR 1.00; 95 %CI 0.89–1.14) versus those with hsCRP ≥2 mg/L (HR 1.04; 95 %CI 0.86–1.25, P<sub>interaction</sub> = 0.79). In line with Lp(a) levels, significant interaction was observed between OxPL-apo(a) as well as OxPL-apoB levels for the composite endpoint with IL-6 (P<sub>interaction</sub>&lt;0.01 and 0.03, respectively), but not for hsCRP.</div></div><div><h3>Conclusions</h3><div>In patients with CCS, Lp(a), OxPL-apo(a) and OxPL-apoB associated cardiovascular risk was only pertinent in those with elevated IL-6 but not hsCRP levels.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"405 ","pages":"Article 119211"},"PeriodicalIF":4.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immune-related biochemical markers and 20-year incidence of atherosclerotic cardiovascular disease: the ATTICA study (2002–2022) 免疫相关生化标志物与动脉粥样硬化性心血管疾病20年发病率:ATTICA研究(2002-2022)
IF 4.9 2区 医学
Atherosclerosis Pub Date : 2025-04-24 DOI: 10.1016/j.atherosclerosis.2025.119212
Sofia-Panagiota Giannakopoulou , Christina Chrysohoou , Smaragdi Antonopoulou , Fotios Barkas , Nikos Vlachogiannis , Evrydiki Kravvariti , Evangelos Liberopoulos , Christos Pitsavos , Costas Tsioufis , Demosthenes Panagiotakos , Petros P. Sfikakis
{"title":"Immune-related biochemical markers and 20-year incidence of atherosclerotic cardiovascular disease: the ATTICA study (2002–2022)","authors":"Sofia-Panagiota Giannakopoulou ,&nbsp;Christina Chrysohoou ,&nbsp;Smaragdi Antonopoulou ,&nbsp;Fotios Barkas ,&nbsp;Nikos Vlachogiannis ,&nbsp;Evrydiki Kravvariti ,&nbsp;Evangelos Liberopoulos ,&nbsp;Christos Pitsavos ,&nbsp;Costas Tsioufis ,&nbsp;Demosthenes Panagiotakos ,&nbsp;Petros P. Sfikakis","doi":"10.1016/j.atherosclerosis.2025.119212","DOIUrl":"10.1016/j.atherosclerosis.2025.119212","url":null,"abstract":"<div><h3>Background and aims</h3><div>Inflammation has been associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. We evaluated immune-related biomarkers regarding their ability, individually and as a composite score, to predict 20-year ASCVD incidence in an apparently healthy adult population.</div></div><div><h3>Methods</h3><div>A cohort of 1270 adults, who were free of ASCVD at baseline, with a 20-year follow-up from the prospective ATTICA study, were included in this analysis. Immune-related biochemical markers independently predictive of 20-year ASCVD risk were identified, and an aggregate biomarker score was developed. The incremental predictive value of this score beyond the SCORE2 was assessed using area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI).</div></div><div><h3>Results</h3><div>Three immune-related biomarkers -interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and fibrinogen-showed the best predictive ability of 20-year ASCVD risk and were subsequently integrated into an aggregate biomarker score (ImmActScore), exhibiting a range from 0 (6 % absolute risk) to 4 (63 % absolute risk). Individual ImmActScore was independently associated with 20-year ASCVD risk (multi-adjusted HR per 1-unit:1.24, 95 %CI:1.05–1.46, <em>p</em> = 0.011). The 38.5 % of the 20-year incident ASCVD could be attributed to ImmActScores of ≥1. Integrating ImmActScore into the SCORE2 model yielded a continuous NRI of 0.603 and a categorical NRI of 18.4 % in the 40–50 year age group.</div></div><div><h3>Conclusions</h3><div>Assessing immune-related pathways may offer additional potential for long-term ASCVD risk stratification. A combined measure of IL-6, TNF-α and fibrinogen levels was associated with ASCVD events over a 20-year period. Further validation in independent cohorts is warranted.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"405 ","pages":"Article 119212"},"PeriodicalIF":4.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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