{"title":"Cholesterol Crystals as Triggers of NLRP3 Inflammasome Activation in Atherosclerosis.","authors":"Mustafa Yalcinkaya, Alan R Tall","doi":"10.1007/s11883-025-01323-w","DOIUrl":"https://doi.org/10.1007/s11883-025-01323-w","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review aims to provide a comprehensive overview of the interplay between cholesterol crystals (CCs), NLRP3 inflammasome activation, and the progression of atherosclerosis.</p><p><strong>Recent findings: </strong>Emerging evidence highlights the critical role of CCs in enhancing plaque inflammation and instability, increasing the risk of rupture or erosion. Early studies focused on the mechanism of lysosomal damage induced by CCs, leading to the release of cathepsin B into the cytoplasm, which in turn triggers NLRP3 inflammasome activation. More recent studies suggest that the trafficking of cholesterol within macrophages activates NLRP3 via CaMKII/JNK signaling, and NLRP3 deubiquitylation. The activation of the complement system by CCs can also contribute to NLRP3 inflammasome activation via changes in mitochondrial energy metabolism and ROS production worsening atherosclerosis. CCs can aggravate atherosclerosis by triggering a complex interplay of pathways, including lysosomal damage, cholesterol trafficking to ER, and complement system activation, all of which converge on the activation of the NLRP3 inflammasome, driving plaque inflammation and instability.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":"27 1","pages":"77"},"PeriodicalIF":5.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759404","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}
Kyle Sheth, Stephanie Kim, Laura Porterfield, Salim S Virani, Shikha Wadhwani, Elizabeth M Vaughan
{"title":"The Expanding Scope of GLP-1 Receptor Agonists: Six Uses Beyond Diabetes.","authors":"Kyle Sheth, Stephanie Kim, Laura Porterfield, Salim S Virani, Shikha Wadhwani, Elizabeth M Vaughan","doi":"10.1007/s11883-025-01319-6","DOIUrl":"10.1007/s11883-025-01319-6","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review summarizes recent advances in the clinical applications of glucagon-like peptide-1 receptor agonists (GLP-1RAs) beyond their established role in glycemic control for type 2 diabetes (T2DM).</p><p><strong>Recent findings: </strong>Originally developed for glycemic control in T2DM, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now being utilized for a range of additional diseases and conditions. Strong evidence supports their efficacy in inducing clinically meaningful weight loss in individuals with overweight or obesity. Further studies have demonstrated cardiovascular benefits, kidney-protective effects, and therapeutic potential in obesity-related conditions such as obstructive sleep apnea and metabolic-associated steatotic liver disease. Emerging data also suggest possible roles in treating substance use disorders, including alcohol and nicotine dependence, though findings remain preliminary and variable. Despite these promising developments, GLP-1RAs are associated with side effects and high costs, contributing to variability in patient access. The therapeutic scope of GLP-1 receptor agonists extends beyond diabetes to multiple other conditions. Broader adoption requires careful evaluation of safety, cost, and evidence for less-established indications.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":"27 1","pages":"76"},"PeriodicalIF":5.2,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741536","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}
{"title":"JAM-A: Adhesion Receptor and Signaling Regulator in Atherosclerosis.","authors":"Mariel F Schwietzer, Klaus Ebnet","doi":"10.1007/s11883-025-01322-x","DOIUrl":"10.1007/s11883-025-01322-x","url":null,"abstract":"<p><strong>Purpose of review: </strong>Cell-cell adhesion between leukocytes, platelets and endothelial cells plays a critical role in vascular inflammation and thrombus formation. This review aims at providing a comprehensive picture of the contribution of the immunoglobulin superfamily (IgSF) cell adhesion receptor Junctional Adhesion Molecule-A (JAM-A) to the process of atherosclerosis.</p><p><strong>Recent findings: </strong>Proinflammatory and proatherogenic stimulation of endothelial cells results in redistribution of JAM-A from cell-cell junctions to the apical surface to promote monocyte adhesion and transmigration. Agonist-stimulation of platelets results in elevated surface levels of JAM-A concomitant with enhanced release of soluble JAM-A (sJAM-A). sJAM-A promotes platelet aggregation, thrombus formation, and platelet-monocyte aggregate formation. Elevated levels of sJAM-A correlate with recurrent myocardial infarction. JAM-A is expressed by several cell types implicated in atherogenesis, notably endothelial cells, platelets, and leukocytes. Proinflammatory and proatherogenic stimuli induce a redistribution of JAM-A within endothelial cells. Stimulated platelets release sJAM-A into the circulation. This review illustrates the role of JAM-A in atherogenesis and elaborates the underlying mechanisms.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":"27 1","pages":"75"},"PeriodicalIF":5.2,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aixue Zou, Yuxuan Sun, Weiwei Dong, Jinjing Lu, Zhiyong Yang
{"title":"Recent Progress of Sterol Regulatory Element-binding Proteins Role in Atherosclerosis.","authors":"Aixue Zou, Yuxuan Sun, Weiwei Dong, Jinjing Lu, Zhiyong Yang","doi":"10.1007/s11883-025-01317-8","DOIUrl":"https://doi.org/10.1007/s11883-025-01317-8","url":null,"abstract":"<p><strong>Purpose of review: </strong>Atherosclerotic cardiovascular disease (ASCVD), influenced by elevated plasma low-density lipoprotein (LDL) and cholesterol levels, is important to various acute cardiovascular and cerebrovascular diseases, causing life-threatening deaths worldwide. Early intervention for atherosclerosis is both essential and beneficial. As members of a class of transcription factors, sterol regulatory element-binding proteins (SREBPs) regulate the expression of most genes involved in lipid metabolism. This review aimed to present three aspects of SREBP regulation in the Endoplasmic Reticulum (ER), Golgi apparatus, and nucleus after maturation. Different subcellular localizations play integral roles in regulating the maturation and activity of SREBPs. Moreover, several drugs that target SREBPs for the treatment of atherosclerosis are described, with the aim of exploring SREBPs as new targets for treating atherosclerosis.</p><p><strong>Recent findings: </strong>There are three members of the SREBP family, namely, SREBP-1a, SREBP-1c, and SREBP-2, all of which have differing functions. SREBP-1a and SREBP-1c regulate the synthesis of fatty acids, while SREBP-2 regulates cholesterol metabolism. SREBPs combine with the SREBP Cleavage-Activating Protein (SCAPs) to form the SCAP/SREBP complex. This complex can bind to and is regulated by insulin-induced genes (INSIG), affecting endoplasmic reticulum (ER)-to-Golgi translocation. SREBPs are sheared by 1-site protease (S1P) and 2-site protease (S2P) in a regular sequence on arrival at the Golgi apparatus, and are processed, matured, and transported to the nucleus for action. The review focuses on how SREBPs, crucial regulators of cholesterol and fatty acid metabolism, are controlled at different cellular locations (ER, Golgi, Nucleus), and explores their potential as drug targets for treating atherosclerosis, a major global health threat driven by high LDL cholesterol.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":"27 1","pages":"74"},"PeriodicalIF":5.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689409","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}
Ali Bin Abdul Jabbar, Maha Inam, Nausharwan Butt, Sadiya S Khan, Sana Sheikh, Adeel Khoja, Benjamin Perry, Gerardo Zavala Gomez, Leandro Slipczuk, Salim S Virani
{"title":"Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) Equations: What Clinicians Need to Know?","authors":"Ali Bin Abdul Jabbar, Maha Inam, Nausharwan Butt, Sadiya S Khan, Sana Sheikh, Adeel Khoja, Benjamin Perry, Gerardo Zavala Gomez, Leandro Slipczuk, Salim S Virani","doi":"10.1007/s11883-025-01320-z","DOIUrl":"https://doi.org/10.1007/s11883-025-01320-z","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review aims to examine the rationale, development, and implications of the newly developed Predicting Risk of CVD EVENTs (PREVENT) equations for cardiovascular disease (CVD) risk assessment.</p><p><strong>Recent findings: </strong>The PREVENT equations were developed from diverse, contemporary, real-world datasets and offer accurate discrimination for predicting risk of total CVD and separately, atherosclerotic CVD (ASCVD) and heart failure (HF). It addresses the nearly twofold overprediction of ASCVD risk with PCEs and includes risk factors related to cardiovascular-kidney-metabolic (CKM) syndrome (body mass index and estimated glomerular filtration rate, with the option to include albumin-creatinine ratio and haemoglobin A1C). Unlike PCEs, PREVENT did not include race as a predictor. PREVENT provides an option to add Social Deprivation Index (SDI) as variable in risk prediction which allows incorporation of social determinants of health. Studies indicate that PREVENT estimates for 10-year ASCVD risk are significantly lower than those obtained using PCEs. PREVENT also has potential to assess HF risk and guide potential therapies in the future for the prevention of HF. The PREVENT equations represent a crucial step forward in personalized CVD risk assessment, addressing limitations of PCEs by incorporating a broader range of CKM risk factors and accounting for social determinants of health. While promising for guiding future preventive strategies and public health initiatives, endorsement by guidelines and effective implementation into clinical workflows will be essential to realize its full potential in reducing the burden of CVD.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":"27 1","pages":"73"},"PeriodicalIF":5.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674095","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}
Marta Biolo, Federica Galimberti, Camilla Portinari, Sandra Bertocco, Paola Tosin, Manuela Casula, Lorenzo Previato, Sabina Zambon, Paolo Simioni, Alberto Zambon
{"title":"ApoC-III as Therapeutic Target: Is it Primetime for Clinical Use?","authors":"Marta Biolo, Federica Galimberti, Camilla Portinari, Sandra Bertocco, Paola Tosin, Manuela Casula, Lorenzo Previato, Sabina Zambon, Paolo Simioni, Alberto Zambon","doi":"10.1007/s11883-025-01315-w","DOIUrl":"https://doi.org/10.1007/s11883-025-01315-w","url":null,"abstract":"<p><strong>Purpose of review: </strong>Apolipoprotein C-III (ApoC-III) plays a pivotal role in triglyceride (TG) metabolism by inhibiting lipoprotein lipase and hepatic clearance of TG-rich lipoproteins, contributing to hypertriglyceridaemia and elevated cardiovascular risk, as well as a high risk of acute pancreatitis. This review aims to summarize current evidence on ApoC-III inhibition strategies.</p><p><strong>Recent findings: </strong>Current treatments targeting Apo C-III include two antisense oligonucleotides (ASOs) (volanesorsen and olezarsen), and a small interfering RNA (siRNA) (plozasiran). Volanesorsen, a second-generation ASO, has shown effectiveness in reducing TG and preventing acute pancreatitis, especially in patients with familial chylomicronemia syndrome (FCS). However, its use is limited by the risk of thrombocytopenia, likely related to its chemical structure rather than ApoC-III inhibition itself. Olezarsen, a third-generation ASO with GalNAc conjugation for targeted liver delivery, offers an improved safety profile and strong efficacy in lowering TG and atherogenic lipoproteins levels, making it a promising candidate for a broader clinical use. Plozasiran, a GalNAc-conjugated siRNA, has shown robust and sustained TG reductions with a favorable safety profile, and early data suggest it may also reduce acute pancreatitis risk. ApoC-III inhibition represents an innovative and effective approach in managing hypertriglyceridaemia and its complications. Further outcome-driven trials are essential to define its role in cardiovascular risk reduction.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":"27 1","pages":"72"},"PeriodicalIF":5.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658649","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}
Christian Haudenchild, Shyon Parsa, Fatima Rodriguez
{"title":"Incidental Finding of Coronary and Non-Coronary Artery Calcium: What Do Clinicians Need To Know?","authors":"Christian Haudenchild, Shyon Parsa, Fatima Rodriguez","doi":"10.1007/s11883-025-01318-7","DOIUrl":"https://doi.org/10.1007/s11883-025-01318-7","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review summarizes the role of incidentally and non-incidentally discovered coronary artery calcification (CAC) and the evolving role of non-coronary artery calcification in atherosclerotic cardiovascular disease (ASCVD) risk assessment. Additionally, this review explores the emerging use of artificial intelligence (AI), machine learning (ML), radiomics, and natural language processing (NLP) for automated detection, quantification, and communication of these incidentally discovered findings.</p><p><strong>Recent findings: </strong>This review summarizes recent findings in the space, including the development of various AI/ML-based approaches for automated calcification quantification and detection. Recent work leverages the use of incidentally discovered CAC and non-coronary calcification (e.g. aortic valve, aortic arch, carotid artery, breast arterial calcification) and their influence on clinical decision-making and prescribing practices. CAC and various forms of non-coronary artery calcifications are increasingly recognized as powerful and additive predictors of ASCVD risk. Advances in AI, ML, and radiomics enable scalable, automated measurement of both incidental and non-incidental CAC and non-coronary calcifications, which will facilitate more precise, personalized ASCVD risk stratification.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":"27 1","pages":"71"},"PeriodicalIF":5.7,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616614","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}
{"title":"Artificial Intelligence-Enabled Point-of-Care Echocardiography: Bringing Precision Imaging to the Bedside.","authors":"Sasha-Ann East, Yanting Wang, Naveena Yanamala, Kameswari Maganti, Partho P Sengupta","doi":"10.1007/s11883-025-01316-9","DOIUrl":"10.1007/s11883-025-01316-9","url":null,"abstract":"<p><strong>Purpose of review: </strong>The integration of artificial intelligence (AI) with point-of-care ultrasound (POCUS) is transforming cardiovascular diagnostics by enhancing image acquisition, interpretation, and workflow efficiency. These advancements hold promise in expanding access to cardiovascular imaging in resource-limited settings and enabling early disease detection through screening applications. This review explores the opportunities and challenges of AI-enabled POCUS as it reshapes the landscape of cardiovascular imaging.</p><p><strong>Recent findings: </strong>AI-enabled systems can reduce operator dependency, improve image quality, and support clinicians-both novice and experienced-in capturing diagnostically valuable images, ultimately promoting consistency across diverse clinical environments. However, widespread adoption faces significant challenges, including concerns around algorithm generalizability, bias, explainability, clinician trust, and data privacy. Addressing these issues through standardized development, ethical oversight, and clinician-AI collaboration will be critical to safe and effective implementation. Looking ahead, emerging innovations-such as autonomous scanning, real-time predictive analytics, tele-ultrasound, and patient-performed imaging-underscore the transformative potential of AI-enabled POCUS in reshaping cardiovascular care and advancing equitable healthcare delivery worldwide.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":"27 1","pages":"70"},"PeriodicalIF":5.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiaming Zhang, Mengkai Lu, Xiuya Guan, Jiaqi Hao, Yunlun Li, Lei Zhang, Chao Li
{"title":"The Role of Lysyl Oxidase in the Pathological Stage of Atherosclerosis: Structural Stabilizer or Disease Driver?","authors":"Jiaming Zhang, Mengkai Lu, Xiuya Guan, Jiaqi Hao, Yunlun Li, Lei Zhang, Chao Li","doi":"10.1007/s11883-025-01312-z","DOIUrl":"https://doi.org/10.1007/s11883-025-01312-z","url":null,"abstract":"<p><strong>Purpose of review: </strong>Atherosclerosis (AS) is a progressive disease characterized by initial lipid deposition, endothelial dysfunction, inflammation, fibrocalcific lesions formation, and ultimately, plaque instability intensified and rupture-one of the major contributors to morbidity and mortality worldwide. The enzymes lysyl oxidase (LOX) and its LOX-like (LOXL) isoforms are copper-dependent amine oxidases that catalyze lysine-derived cross-linking in collagen and elastin, playing indispensable roles in extracellular matrix (ECM) homeostasis. This review aims to summarize current insights into the roles of LOX/LOXL in AS pathogenesis and their potential as therapeutic targets.</p><p><strong>Recent findings: </strong>Recent studies have revealed that the LOX family exerts dual effects on the progression of AS, such as early endothelial dysfunction, vascular smooth muscle cell (VSMC) phenotypic switching, and fibrous cap stability. Dysregulated LOX expression, induced by low-density lipoprotein (LDL), low shear stress, and hormonal regulation, can worsen endothelial damage, while LOX activity may also have anti-atherogenic effects: it promotes the formation of stable fibrous cap. The LOX family contributes to both the progression and stabilization of atherosclerotic lesions through complex and stage-specific mechanisms. Understanding these multifaceted roles opens new avenues for developing LOX-targeted therapies aimed at improving plaque stability and reducing AS-related cardiovascular events.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":"27 1","pages":"69"},"PeriodicalIF":5.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567256","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}