Arteriosclerosis, Thrombosis, and Vascular Biology最新文献

{"title":"Adding a New Piece to the ASGR1 Puzzle: ANGPTL3.","authors":"Itsaso Garcia-Arcos","doi":"10.1161/ATVBAHA.124.321882","DOIUrl":"10.1161/ATVBAHA.124.321882","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"2450-2452"},"PeriodicalIF":7.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543370","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":"Immune-Mediated Inflammatory Diseases, Dyslipidemia, and Cardiovascular Risk: A Complex Interplay.","authors":"Michael J Wilkinson, Michael D Shapiro","doi":"10.1161/ATVBAHA.124.319983","DOIUrl":"10.1161/ATVBAHA.124.319983","url":null,"abstract":"<p><p>Individuals with autoimmune inflammatory diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and psoriasis, are at increased risk for cardiovascular disease. While these diseases share common features of systemic inflammation, the impact of individual autoimmune inflammatory conditions on circulating lipids and lipoproteins varies by specific disease, disease activity, and the immune-suppressing medications used to treat these conditions. A common feature observed in many autoimmune inflammatory diseases is the development of a proatherogenic dyslipidemic state, characterized by dysfunctional HDLs (high-density lipoproteins) and increased oxidation of LDLs (low-density lipoproteins). Various disease-modifying antirheumatic drugs also have complex and variable effects on lipids, and it is critical to take this into consideration when evaluating lipid-related risk in individuals with immune-mediated inflammatory conditions. This review aims to critically evaluate the current understanding of the relationship between immune-mediated inflammatory diseases and dyslipidemia, the underlying mechanisms contributing to atherogenesis, and the impact of various pharmacotherapies on lipid profiles and cardiovascular risk. We also discuss the role of lipid-lowering therapies, particularly statins, in managing residual risk in this high-risk population and explore the potential of emerging therapies with complementary anti-inflammatory and lipid-lowering effects.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"2396-2406"},"PeriodicalIF":7.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543372","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":"Whys and Wherefores of Coronary Arterial Positive Remodeling.","authors":"Carlotta Onnis, Renu Virmani, Anna Madra, Valentina Nardi, Rodrigo Salgado, Roberta Montisci, Riccardo Cau, Alberto Boi, Amir Lerman, Carlo N De Cecco, Peter Libby, Luca Saba","doi":"10.1161/ATVBAHA.124.321504","DOIUrl":"10.1161/ATVBAHA.124.321504","url":null,"abstract":"<p><p>Positive remodeling (PR) is an atherosclerotic plaque feature defined as an increase in arterial caliber at the level of an atheroma, in response to increasing plaque burden. The mechanisms that lead to its formation are incompletely understood, but its role in coronary atherosclerosis has major clinical implications. Indeed, plaques with PR have elevated risk of provoking acute cardiac events. Hence, PR figures among the high-risk plaque features that cardiac imaging studies should report. This review aims to provide an overview of the current literature on coronary PR. It outlines the pathophysiology of PR, the different techniques used to assess its presence, and the imaging findings associated to PR, on both noninvasive and invasive studies. This review also summarizes clinical observations, trials, and studies, focused on the impact of PR on clinical outcome.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"2416-2427"},"PeriodicalIF":7.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11594009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543373","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":"CXCR3-CXCL11 Signaling Restricts Angiogenesis and Promotes Pericyte Recruitment.","authors":"Jihui Lee, Megan E Goeckel, Allison Levitas, Sarah Colijn, Jimann Shin, Anna Hindes, Geonyoung Mun, Zarek Burton, Bharadwaj Chintalapati, Ying Yin, Javier Abello, Lilianna Solnica-Krezel, Amber N Stratman","doi":"10.1161/ATVBAHA.124.321434","DOIUrl":"10.1161/ATVBAHA.124.321434","url":null,"abstract":"<p><strong>Background: </strong>Endothelial cell (EC)-pericyte interactions are known to remodel in response to hemodynamic forces; yet there is a lack of mechanistic understanding of the signaling pathways that underlie these events. Here, we have identified a novel signaling network regulated by blood flow in ECs-the chemokine receptor CXCR3 (CXC motif chemokine receptor 3) and one of its ligands, CXCL11 (CXC motif chemokine ligand 11)-that delimits EC angiogenic potential and promotes pericyte recruitment to ECs during development.</p><p><strong>Methods: </strong>We investigated the role of CXCR3 on vascular development using both 2- and 3-dimensional in vitro assays, to study EC-pericyte interactions and EC behavioral responses to blood flow. Additionally, genetic mutants and pharmacological modulators were used in zebrafish in vivo to study the impacts of CXCR3 loss and gain of function on vascular development.</p><p><strong>Results: </strong>In vitro modeling of EC-pericyte interactions demonstrates that suppression of EC-specific CXCR3 signaling leads to loss of pericyte association with EC tubes. In vivo, phenotypic defects are particularly noted in the cranial vasculature, where we see a loss of pericyte association with ECs and expansion of the vasculature in zebrafish treated with the Cxcr3 inhibitor AMG487 or in homozygous <i>cxcr3.1/3.2/3.3</i> triple mutants. We also demonstrate that CXCR3-deficient ECs are more elongated, move more slowly, and have impaired EC-EC junctions compared with their control counterparts.</p><p><strong>Conclusions: </strong>Our results suggest that CXCR3 signaling in ECs helps promote vascular stabilization events during development by preventing EC overgrowth and promoting pericyte recruitment.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"2577-2595"},"PeriodicalIF":7.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11594002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364167","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":"Elucidating VEGF Biology: A Journey of Discovery and Clinical Translation.","authors":"Tommaso Mori, Naresh Kumar R N, Napoleone Ferrara","doi":"10.1161/ATVBAHA.124.319574","DOIUrl":"10.1161/ATVBAHA.124.319574","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":"44 12","pages":"2361-2365"},"PeriodicalIF":7.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738150","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 Meta-Analysis Uncovers the Pancreatic Endothelial Cell Transcriptomic Signature and Reveals a Key Role for NKX2-3 in PLVAP Expression.","authors":"Safwat T Khan, Neha Ahuja, Sonia Taïb, Shabana Vohra, Ondine Cleaver, Sara S Nunes","doi":"10.1161/ATVBAHA.124.321781","DOIUrl":"10.1161/ATVBAHA.124.321781","url":null,"abstract":"<p><strong>Background: </strong>The pancreatic vasculature displays tissue-specific physiological and functional adaptations that support rapid insulin response by β-cells. However, the digestive enzymes have made it difficult to characterize pancreatic endothelial cells (ECs), resulting in the poor understanding of pancreatic EC specialization.</p><p><strong>Methods: </strong>Available single-nuclei/single-cell RNA-sequencing data sets were mined to identify pancreatic EC-enriched signature genes and to develop an integrated atlas of human pancreatic ECs. We validated the findings using independent single-nuclei/single-cell RNA-sequencing data, bulk RNA-sequencing data of isolated ECs, spatial transcriptomics data, immunofluorescence, and RNAScope of selected markers. The NK2 homeobox 3 (NKX2-3) TF (transcription factor) was expressed in HUVECs via gene transfection, and the expression of pancreatic EC-enriched signature genes was assessed via RT-qPCR.</p><p><strong>Results: </strong>We defined a pancreatic EC-enriched gene signature conserved across species and developmental stages that included genes involved in ECM (extracellular matrix) composition (COL15A1 and COL4A1), permeability and barrier function (PLVAP, EHD4, CAVIN3, HSPG2, ROBO4, HEG1, and CLEC14A), and key signaling pathways (S1P [sphingosine-1-phosphate], TGF-β [transforming growth factor-β], RHO/RAC GTPase [guanosine triphosphatase], PI3K/AKT [phosphoinositide 3-kinase/protein kinase B], and PDGF [platelet-derived growth factor]). The integrated atlas revealed the vascular hierarchy within the pancreas. We identified and validated a specialized islet capillary subpopulation characterized by genes involved in permeability (PLVAP and EHD4), immune-modulation (FABP5, HLA-C, and B2M), ECM composition (SPARC and SPARCL1), IGF (insulin-like growth factor) signaling (IGFBP7), and membrane transport (SLCO2A1, SLC2A3, and CD320). Importantly, we identified NKX2-3 as a key TF enriched in pancreatic ECs. DNA-binding motif analysis found NKX2-3 motifs in ≈40% of the signature genes. Induction of NKX2-3 in HUVECs promoted the expression of the islet capillary EC-enriched genes PLVAP and SPARCL1.</p><p><strong>Conclusions: </strong>We defined a validated transcriptomic signature of pancreatic ECs and uncovered their intratissue transcriptomic heterogeneity. We showed that NKX2-3 acts upstream of PLVAP and provided a single-cell online resource that can be further explored by the community: https://vasconcelos.shinyapps.io/pancreatic_endothelial/.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"2596-2615"},"PeriodicalIF":7.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11594071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493711","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":"A Sophisticated Model of Human Atherosclerosis on a Chip.","authors":"Brandon J Tefft","doi":"10.1161/ATVBAHA.124.321804","DOIUrl":"10.1161/ATVBAHA.124.321804","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"2473-2475"},"PeriodicalIF":7.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Dimensional Single-Cell Mass Cytometry Demonstrates Differential Platelet Functional Phenotypes in Infants With Congenital Heart Disease.","authors":"Sean X Gu, Brian S Marcus, Vivian W Gu, Adarsh P Varghese, John Hwa, E Vincent S Faustino","doi":"10.1161/ATVBAHA.124.321131","DOIUrl":"10.1161/ATVBAHA.124.321131","url":null,"abstract":"<p><strong>Background: </strong>Congenital heart disease (CHD) is a group of complex heart defects associated with hematologic abnormalities, including increased risk of thrombotic and bleeding events. Past studies have observed evidence of platelet hyperreactivity, while other studies showed decreased platelet activation in patients with CHD. The goal of this study was to develop a mass spectrometry approach to characterize single platelets in infants with CHD and identify potential etiology for such discrepant results.</p><p><strong>Methods: </strong>We enrolled 19 infants with CHD along with 21 non-CHD controls at Yale New Haven Children's Heart Center. A single-cell high-dimensional mass cytometry method was developed to quantitatively interrogate platelet surface markers in whole blood. Additionally, plasma cytokine analysis was performed through a multiplexed panel of 52 vascular and inflammatory markers to assess for platelet releasates.</p><p><strong>Results: </strong>We found that infants with CHD had significant differences in platelet activation and functional markers by mass cytometry compared with non-CHD controls. Based on cell surface markers, we classified the platelets into 8 subpopulations (P0 to P7). Distinct subpopulations of platelets (P1, P4, and P5) exhibiting decreased aggregatory phenotype but altered secretory phenotypes were also identified and found to be more abundant in the blood of infants with CHD. Electron microscopy identified increased proportion of hypogranular platelets in CHD. Moreover, cytokine analysis demonstrated an overall increase in plasma cytokines and biomarkers in CHD, including IL (interleukin)-6, IL-8, IL-27, RANTES (regulated upon activation, normal T cell expressed and secreted), and VWF (von Willebrand factor), which are expressed in platelet granules and can be released upon activation.</p><p><strong>Conclusions: </strong>We developed a robust mass cytometry approach to identify platelet phenotypic heterogeneity. Infants with CHD had alterations in distinct subpopulations of platelets with overall reduced aggregatory phenotype and secretory dysfunction. These findings suggest that platelets in infants with CHD may be exhausted due to persistent stimulation and may explain both bleeding and thrombotic vascular complications associated with CHD.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"2530-2539"},"PeriodicalIF":7.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016223","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":"Lipoprotein Apheresis: Utility, Outcomes, and Implementation in Clinical Practice: A Scientific Statement From the American Heart Association.","authors":"Eugenia Gianos, P Barton Duell, Peter P Toth, Patrick M Moriarty, Gilbert R Thompson, Eliot A Brinton, Lisa C Hudgins, Mary Nametka, Kathleen H Byrne, Geetha Raghuveer, Prashant Nedungadi, Laurence S Sperling","doi":"10.1161/ATV.0000000000000177","DOIUrl":"10.1161/ATV.0000000000000177","url":null,"abstract":"<p><p>Despite the availability of multiple classes of lipoprotein-lowering medications, some high-risk patients have persistent hypercholesterolemia and may require nonpharmacologic therapy. Lipoprotein apheresis (LA) is a valuable but underused adjunctive therapeutic option for low-density lipoprotein cholesterol and lipoprotein(a) lowering, particularly in children and adults with familial hypercholesterolemia. In addition to lipid lowering, LA reduces serum levels of proinflammatory and prothrombotic factors, reduces blood viscosity, increases microvascular myocardial perfusion, and may provide beneficial effects on endothelial function. Multiple observational studies demonstrate strong evidence for improved cardiovascular outcomes with LA; however, use in the United States is limited to a fraction of its Food and Drug Administration-approved indications. In addition, there are limited data regarding LA benefit for refractory focal segmental glomerulosclerosis. In this scientific statement, we review the history of LA, mechanisms of action, cardiovascular and renal outcomes data, indications, and options for treatment.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e304-e321"},"PeriodicalIF":7.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cure of Congenital Purpura Fulminans via Expression of Engineered Protein C Through Neonatal Genome Editing in Mice.","authors":"Tomoki Togashi, Nemekhbayar Baatartsogt, Yasumitsu Nagao, Yuji Kashiwakura, Morisada Hayakawa, Takafumi Hiramoto, Takayuki Fujiwara, Eriko Morishita, Osamu Nureki, Tsukasa Ohmori","doi":"10.1161/ATVBAHA.123.319460","DOIUrl":"10.1161/ATVBAHA.123.319460","url":null,"abstract":"<p><strong>Background: </strong>PC (protein C) is a plasma anticoagulant encoded by <i>PROC</i>; mutation in both <i>PROC</i> alleles results in neonatal purpura fulminans-a fatal systemic thrombotic disorder. In the present study, we aimed to develop a genome editing treatment to cure congenital PC deficiency.</p><p><strong>Methods: </strong>We generated an engineered APC (activated PC) to insert a furin-cleaving peptide sequence between light and heavy chains. The engineered PC was expressed in the liver of mice using an adeno-associated virus vector or CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9)-mediated genome editing using an adeno-associated virus vector in vivo.</p><p><strong>Results: </strong>The engineered PC could be released in its activated form and significantly prolonged the plasma coagulation time independent of the cofactor activity of PS (protein S) in vitro. The adeno-associated virus vector-mediated expression of the engineered PC, but not wild-type PC, prolonged coagulation time owing to the inhibition of activated coagulation FV (factor V) in a dose-dependent manner and abolished pathological thrombus formation in vivo in C57BL/6J mice. The insertion of <i>EGFP</i> (enhanced green fluorescent protein) sequence conjugated with self-cleaving peptide sequence at <i>Alb</i> locus via neonatal in vivo genome editing using adeno-associated virus vector resulted in the expression of EGFP in 7% of liver cells, mainly via homology-directed repair, in mice. Finally, we succeeded in improving the survival of PC-deficient mice by expressing the engineered PC via neonatal genome editing in vivo.</p><p><strong>Conclusions: </strong>These results suggest that the expression of engineered PC via neonatal genome editing is a potential cure for severe congenital PC deficiency.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"2616-2627"},"PeriodicalIF":7.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11594008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589776","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}