JACC: Basic to Translational Science最新文献

{"title":"Monocyte Transcriptional Reprogramming Explains Refractory In-Stent Restenosis","authors":"Joseph Bednarek PhD, Juan Ibla MD, Edward B. Thorp PhD","doi":"10.1016/j.jacbts.2026.101693","DOIUrl":"10.1016/j.jacbts.2026.101693","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 9","pages":"Article 101693"},"PeriodicalIF":8.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148854481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Cardiac Fibrosis and Fibroblast Activation in Amyloid Light Chain (AL) Amyloidosis","authors":"Shingo Narita MD, PhD,&nbsp;John Isaiah Jimenez BS,&nbsp;Nixuan Cai MS,&nbsp;Hiroki Kitakata MD, PhD,&nbsp;Sharmila Dorbala MD,&nbsp;Y. Joseph Woo MD,&nbsp;Kevin M. Alexander MD,&nbsp;Ronglih Liao PhD","doi":"10.1016/j.jacbts.2026.101653","DOIUrl":"10.1016/j.jacbts.2026.101653","url":null,"abstract":"<div><div>Recent studies suggest that interactions between collagen and amyloid fibril may influence amyloid formation, matrix remodeling, and disease progression in cardiac amyloid light chain (AL) amyloidosis. However, the precise pathophysiological mechanisms underlying fibrosis remain largely unexplored. Here, we performed transcriptome analysis of myocardial samples from patients with AL amyloidosis and identified upregulation of fibroblast activation genes, such as collagen type I/III and periostin. Histology showed predominantly type III collagen fibrosis, accompanied by cardiac fibroblasts present within the interstitial myocardium, including areas with amyloidogenic light chain (AL-LC). We further demonstrated a partial fibroblast-to-myofibroblast transition (FMT) in vitro by stimulating cardiac fibroblasts with AL-LC. This indicates that pathogenic AL-LC directly induces fibroblast activation and that matrix remodeling accelerates during amyloid fibril deposition. This extensive cellular and molecular characterization provides novel insights into the essential role of fibrotic pathology in AL cardiomyopathy and may enable the discovery of biomarkers and therapeutic targets.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 9","pages":"Article 101653"},"PeriodicalIF":8.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148855114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Transcriptomics Reveals the Immune Pathogenesis of Isolated Coronary Arteritis Presenting as Refractory In-Stent Restenosis","authors":"Miao Yu MD,&nbsp;Yu Jiang MD,&nbsp;Ji Huang MD, PhD,&nbsp;Zhi-Yao Wei MD,&nbsp;Zhi-Feng Song MD,&nbsp;Fang-Shun Tan MD,&nbsp;Si-Zhuang Huang MD,&nbsp;Jian-Song Yuan MD,&nbsp;Shao-Dong Ye MD,&nbsp;Jin-Gang Cui MD,&nbsp;Han-Jun Zhao MD,&nbsp;Li-Jian Gao MD,&nbsp;Hong-Zhao You MD, PhD,&nbsp;Yan Zeng MD,&nbsp;Wei-Xian Yang MD, PhD,&nbsp;Hai-Yan Qian MD, PhD","doi":"10.1016/j.jacbts.2026.101639","DOIUrl":"10.1016/j.jacbts.2026.101639","url":null,"abstract":"&lt;div&gt;&lt;ul&gt;&lt;li&gt;&lt;span&gt;•&lt;/span&gt;&lt;span&gt;&lt;div&gt;This study provides the first single-cell transcriptomic characterization of refractory recurrent in-stent restenosis (RISR) using coronary artery blood, revealing immune dysregulation as a key driver rather than traditional mechanical mechanisms.&lt;/div&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;•&lt;/span&gt;&lt;span&gt;&lt;div&gt;Single-cell analysis identifies AP-1–driven monocyte inflammatory activation as a central upstream regulator of vascular smooth muscle cell dysfunction and neointimal hyperplasia.&lt;/div&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;•&lt;/span&gt;&lt;span&gt;&lt;div&gt;Monocyte-specific inhibition of AP-1 via conditional Fos deletion significantly reduces neointimal formation in vivo, demonstrating its causal role in restenosis progression.&lt;/div&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;•&lt;/span&gt;&lt;span&gt;&lt;div&gt;These findings highlight monocyte-centered inflammation as a promising therapeutic target for refractory restenosis.&lt;/div&gt;&lt;/span&gt;&lt;/li&gt;&lt;/ul&gt;&lt;/div&gt;&lt;div&gt;&lt;div&gt;The aim of the present study was to elucidate the cellular and molecular mechanisms underlying refractory recurrent in-stent restenosis (RISR), thereby facilitating the identification of potential therapeutic targets. Coronary blood samples were obtained from culprit lesions of patients with RISR and non-ISR controls and subjected to single-cell RNA sequencing to comprehensively characterize immune cell heterogeneity and identify pathogenic signaling pathways. Key molecular mechanisms were validated in independent clinical samples using flow cytometry, monocyte-vascular smooth muscle cell (VSMC) coculture systems, and in vitro functional assays. Causality was further assessed using a monocyte-specific Fos knockdown mouse model of carotid wire injury to evaluate its role in vascular remodeling. Results revealed a pronounced inflammatory immune signature in RISR, with marked upregulation of activator protein-1 (AP-1) gene expression and transcriptional activity in monocytes as a central feature. Upstream mechanistic analyses identified the CCL5-CCR1/p38 MAPK axis as a key driver of AP-1 activation, promoting proinflammatory cytokine release and inducing a proliferative phenotypic switch in VSMCs. In vivo, monocyte-specific Fos knockdown significantly attenuated neointimal hyperplasia and luminal stenosis following vascular injury. Targeting monocyte AP-1 signaling may represent a novel therapeutic strategy for refractory restenosis driven by localized coronary inflammation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;The aim of the present study was to elucidate the cellular and molecular mechanisms underlying refractory recurrent in-stent restenosis (RISR), thereby facilitating the identification of potential therapeutic targets. Coronary blood samples were obtained from culprit lesions of patients with RISR and non-ISR controls and subjected to single-cell RNA sequencing to comprehensively characterize immune cell heterogeneity and identify pathogenic signaling pathways. Key molecular mechanisms were validated in independent clinical samples using flow cytom","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 9","pages":"Article 101639"},"PeriodicalIF":8.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ontogeny and Identity of Tissue Macrophages in Human Aging","authors":"Matthias Nahrendorf MD, PhD (Editor-in-Chief, JACC: Basic to Translational Science)","doi":"10.1016/j.jacbts.2026.101701","DOIUrl":"10.1016/j.jacbts.2026.101701","url":null,"abstract":"<div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (65KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 9","pages":"Article 101701"},"PeriodicalIF":8.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Estrogen–IL-33 Circuit in Aortic Fibroblasts Underlies Sex Differences in Tregs in Abdominal Aortic Aneurysm","authors":"Wangling Hu MD,&nbsp;Jingyong Li MD, PhD,&nbsp;Luna Zhai MD, PhD,&nbsp;Zhuo Chen MD,&nbsp;Linwei Ye MD,&nbsp;Ni Xia MD, PhD,&nbsp;Tingting Tang MD, PhD,&nbsp;Shaofang Nie MD, PhD,&nbsp;Min Zhang MD, PhD,&nbsp;Jiao Jiao MD, PhD,&nbsp;Bingjie Lv MD, PhD,&nbsp;Fen Yang MD, PhD,&nbsp;Yuzhi Lu MD, PhD,&nbsp;Lingfeng Zha MD, PhD,&nbsp;Muyang Gu MD, PhD,&nbsp;Xiajun Hu MD, PhD,&nbsp;Shuang Wen MD, PhD,&nbsp;Dan Li MD, PhD,&nbsp;Desheng Hu MD, PhD,&nbsp;Weimin Wang PhD,&nbsp;Xiang Cheng MD, PhD","doi":"10.1016/j.jacbts.2026.101675","DOIUrl":"10.1016/j.jacbts.2026.101675","url":null,"abstract":"<div><div>Regulatory T cells (Tregs) are key components of the vascular immune microenvironment in abdominal aortic aneurysm (AAA), but their sexual dimorphism and underlying mechanisms remain unclear. This study aimed to characterize Treg sex dimorphism in AAA and delineate the governing hormonal and immunologic pathways. Female mice showed reduced aortic Treg infiltration with decreased activation markers (ST2, KLRG1) and the functional mediators interleukin (IL)-10 and trefoil factor 1. Transcriptomic profiling revealed that male aortic Tregs displayed authentic tissue-resident signatures, whereas female aortic Tregs transcriptomically resembled splenic Tregs. Mechanistically, male-biased inflammation stimulated fibroblast IL-33 production via the nuclear factor-κB (NF-κB) pathway, promoting ST2⁺ Treg expansion, whereas estrogen signaling through estrogen receptor-α suppressed NF-κB activation (reduced P65 phosphorylation and nuclear translocation), lowering microenvironmental IL-33 and limiting Treg responses. Notably, Treg depletion did not exacerbate female AAA, indicating a minor Treg role for female pathogenesis. Our findings establish a novel estrogen receptor α/NF-κB/IL-33 axis in fibroblasts governing Treg sex dimorphism in AAA.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 9","pages":"Article 101675"},"PeriodicalIF":8.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148855113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensing Danger After Reperfusion","authors":"Cong Luo MD, PhD,&nbsp;Matthew DeBerge PhD,&nbsp;Holger Eltzschig MD, PhD","doi":"10.1016/j.jacbts.2026.101657","DOIUrl":"10.1016/j.jacbts.2026.101657","url":null,"abstract":"<div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (144KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span><span><span><p>Cong Luo</p></span></span></figure></span><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (251KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span><span><span><p>Matthew DeBerge</p></span></span></figure></span><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (207KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span><span><span><p>Holger Eltzschig</p></span></span></figure></span></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 9","pages":"Article 101657"},"PeriodicalIF":8.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rates of Lipoprotein(a) Oxidation Accelerate at Elevated Levels and Attenuate With Atorvastatin Active Metabolites Compared With Other Statins","authors":"Samuel C.R. Sherratt PhD,&nbsp;Peter Libby MD,&nbsp;Deepak L. Bhatt MD, MPH, MBA,&nbsp;R. Preston Mason PhD, MBA","doi":"10.1016/j.jacbts.2026.101664","DOIUrl":"10.1016/j.jacbts.2026.101664","url":null,"abstract":"<div><div>Lipoprotein(a) [Lp(a)] levels are associated with increased cardiovascular risk, possibly linked to its oxidized phospholipid content that may accelerate lipoprotein oxidation. Attenuating this process could reduce Lp(a) atherogenicity. Atorvastatin is metabolized into 2 hydroxylated metabolites, which account for low-density lipoprotein reduction and potential antioxidant activity. We compared these metabolites' effects to other active statins on oxidation of plasma samples enriched with various levels of Lp(a) or other apolipoprotein B particles, as well as lipid membranes enriched with cholesterol. Lp(a) oxidized more rapidly than other apolipoprotein B particles and accelerated in a nonlinear fashion at levels associated with cardiovascular risk. The metabolites inhibited oxidation of each fraction in contrast to other statins and consistent with cholesterol-enriched membranes. The metabolites' unique phenoxy group facilitated membrane partitioning, leading to free radical scavenging activity as compared with other statins. The antioxidant actions of atorvastatin metabolites may reduce the atherogenicity of Lp(a) in patients independent of their levels.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 9","pages":"Article 101664"},"PeriodicalIF":8.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148855112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Full Issue PDF","authors":"","doi":"10.1016/S2452-302X(26)00247-0","DOIUrl":"10.1016/S2452-302X(26)00247-0","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 9","pages":"Article 101723"},"PeriodicalIF":8.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Board/Officers Page","authors":"","doi":"10.1016/S2452-302X(26)00242-1","DOIUrl":"10.1016/S2452-302X(26)00242-1","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 9","pages":"Article 101718"},"PeriodicalIF":8.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the Fibrils","authors":"Gregory N. Milburn PhD","doi":"10.1016/j.jacbts.2026.101689","DOIUrl":"10.1016/j.jacbts.2026.101689","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 9","pages":"Article 101689"},"PeriodicalIF":8.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148855115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}