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dc.creatorLu, Yifan
dc.creatorSun, Yu
dc.creatorXU, KEMAN
dc.creatorSaaoud, Fatma
dc.creatorShao, Ying
dc.creatorDrummer, Charles, IV
dc.creatorWu, Sheng
dc.creatorHu, Wenhui
dc.creatorYu, Jun
dc.creatorKunapuli, Satya P.
dc.creatorBethea, John R.
dc.creatorVasquez-Padron, Roberto I.
dc.creatorSun, Jianxin
dc.creatorJiang, Xiaohua
dc.creatorWang, Hong
dc.creatorYang, Xiaofeng
dc.identifier.citationLu Y, Sun Y, Xu K, Saaoud F, Shao Y, Drummer C IV, Wu S, Hu W, Yu J, Kunapuli SP, Bethea JR, Vazquez-Padron RI, Sun J, Jiang X, Wang H and Yang X (2022) Aorta in Pathologies May Function as an Immune Organ by Upregulating Secretomes for Immune and Vascular Cell Activation, Differentiation and Trans-Differentiation—Early Secretomes may Serve as Drivers for Trained Immunity. Front. Immunol. 13:858256. doi: 10.3389/fimmu.2022.858256
dc.description.abstractTo determine whether aorta becomes immune organ in pathologies, we performed transcriptomic analyses of six types of secretomic genes (SGs) in aorta and vascular cells and made the following findings: 1) 53.7% out of 21,306 human protein genes are classified into six secretomes, namely, canonical, caspase 1, caspase 4, exosome, Weibel–Palade body, and autophagy; 2) Atherosclerosis (AS), chronic kidney disease (CKD) and abdominal aortic aneurysm (AAA) modulate six secretomes in aortas; and Middle East Respiratory Syndrome Coronavirus (MERS-CoV, COVID-19 homologous) infected endothelial cells (ECs) and angiotensin-II (Ang-II) treated vascular smooth muscle cells (VSMCs) modulate six secretomes; 3) AS aortas upregulate T and B cell immune SGs; CKD aortas upregulate SGs for cardiac hypertrophy, and hepatic fibrosis; and AAA aorta upregulate SGs for neuromuscular signaling and protein catabolism; 4) Ang-II induced AAA, canonical, caspase 4, and exosome SGs have two expression peaks of high (day 7)-low (day 14)-high (day 28) patterns; 5) Elastase induced AAA aortas have more inflammatory/immune pathways than that of Ang-II induced AAA aortas; 6) Most disease-upregulated cytokines in aorta may be secreted via canonical and exosome secretomes; 7) Canonical and caspase 1 SGs play roles at early MERS-CoV infected ECs whereas caspase 4 and exosome SGs play roles in late/chronic phases; and the early upregulated canonical and caspase 1 SGs may function as drivers for trained immunity (innate immune memory); 8) Venous ECs from arteriovenous fistula (AVF) upregulate SGs in five secretomes; and 9) Increased some of 101 trained immunity genes and decreased trained tolerance regulator IRG1 participate in upregulations of SGs in atherosclerotic, Ang-II induced AAA and CKD aortas, and MERS-CoV infected ECs, but less in SGs upregulated in AVF ECs. IL-1 family cytokines, HIF1α, SET7 and mTOR, ROS regulators NRF2 and NOX2 partially regulate trained immunity genes; and NRF2 plays roles in downregulating SGs more than that of NOX2 in upregulating SGs. These results provide novel insights on the roles of aorta as immune organ in upregulating secretomes and driving immune and vascular cell differentiations in COVID-19, cardiovascular diseases, inflammations, transplantations, autoimmune diseases and cancers.
dc.format.extent30 pages
dc.relation.ispartofFaculty/ Researcher Works
dc.relation.haspartFrontiers in Immunology, Vol. 13
dc.relation.isreferencedbyFrontiers Media
dc.rightsAttribution CC BY
dc.subjectEndothelial cell
dc.subjectCanonical and noncanonical secretomes
dc.subjectCoronavirus infection
dc.titleAorta in Pathologies May Function as an Immune Organ by Upregulating Secretomes for Immune and Vascular Cell Activation, Differentiation and Trans-Differentiation—Early Secretomes may Serve as Drivers for Trained Immunity
dc.type.genreJournal article
dc.contributor.groupCardiovascular Research Center (Temple University)
dc.contributor.groupCenter for Metabolic Disease Research (Temple University)
dc.contributor.groupSol Sherry Thrombosis Research Center (Temple University)
dc.description.departmentCardiovascular Sciences
dc.description.departmentBiomedical Education and Data Science
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact
dc.description.schoolcollegeLewis Katz School of Medicine
dc.temple.creatorLu, Yifan
dc.temple.creatorSun, Yu
dc.temple.creatorXu, Keman
dc.temple.creatorSaaoud, Fatma
dc.temple.creatorShao, Ying
dc.temple.creatorDrummer, Charles, IV
dc.temple.creatorWu, Sheng
dc.temple.creatorHu, Wenhui
dc.temple.creatorYu, Jun
dc.temple.creatorKunapuli, Satya P.
dc.temple.creatorJiang, Xiaohua
dc.temple.creatorWang, Hong
dc.temple.creatorYang, Xiaofeng

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