Journal of molecular and cellular cardiology最新文献

{"title":"Quantitative label-free digital holographic imaging of cardiomyocyte optical volume, nucleation, and cell division","authors":"Herman Huang ,&nbsp;Sangsoon Park ,&nbsp;Ines Ross ,&nbsp;Joseph Moreno ,&nbsp;Sheamin Khyeam ,&nbsp;Jacquelyn Simmons ,&nbsp;Guo N. Huang ,&nbsp;Alexander Y. Payumo","doi":"10.1016/j.yjmcc.2024.09.003","DOIUrl":"10.1016/j.yjmcc.2024.09.003","url":null,"abstract":"<div><p>Cardiac regeneration in newborn rodents depends on the ability of pre-existing cardiomyocytes to proliferate and divide. This capacity is lost within the first week of postnatal development when these cells rapidly switch from hyperplasia to hypertrophy, withdraw from the cell cycle, become binucleated, and increase in size. How these dynamic changes in cell size and nucleation impact cardiomyocyte proliferative potential is not well understood. In this study, we innovate the application of a commercially available digital holographic imaging microscope, the Holomonitor M4, to evaluate the proliferative responses of mononucleated and binucleated cardiomyocytes after CHIR99021 treatment, a model proliferative stimulus. This system enables long-term label-free quantitative tracking of primary cardiomyocyte dynamics in real-time with single-cell resolution. Our results confirm that chemical inhibition of glycogen synthase kinase 3 with CHIR99021 promotes complete cell division of both mononucleated and binucleated cardiomyocytes with high frequency. Quantitative tracking of cardiomyocyte volume dynamics during these proliferative events revealed that both mononucleated and binucleated cardiomyocytes reach a similar size-increase threshold prior to attempted cell division. Binucleated cardiomyocytes attempt to divide with lower frequency than mononucleated cardiomyocytes, which may be associated with inadequate increases in cell size. By defining the interrelationship between cardiomyocyte size, nucleation, and cell cycle control, we may better understand the cellular mechanisms that drive the loss of mammalian cardiac regenerative capacity after birth.</p></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"196 ","pages":"Pages 94-104"},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0022282824001457/pdfft?md5=e3e8bd168c1b2980f60aacfa736715f4&pid=1-s2.0-S0022282824001457-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142227393","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}

{"title":"Integrated multi-omics analysis identifies features that predict human pluripotent stem cell-derived progenitor differentiation to cardiomyocytes","authors":"Aaron D. Simmons ,&nbsp;Claudia Baumann ,&nbsp;Xiangyu Zhang ,&nbsp;Timothy J. Kamp ,&nbsp;Rabindranath De La Fuente ,&nbsp;Sean P. Palecek","doi":"10.1016/j.yjmcc.2024.08.007","DOIUrl":"10.1016/j.yjmcc.2024.08.007","url":null,"abstract":"<div><p>Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are advancing cardiovascular development and disease modeling, drug testing, and regenerative therapies. However, hPSC-CM production is hindered by significant variability in the differentiation process. Establishment of early quality markers to monitor lineage progression and predict terminal differentiation outcomes would address this robustness and reproducibility roadblock in hPSC-CM production. An integrated transcriptomic and epigenomic analysis assesses how attributes of the cardiac progenitor cell (CPC) affect CM differentiation outcome. Resulting analysis identifies predictive markers of CPCs that give rise to high purity CM batches, including <em>TTN</em>, <em>TRIM55</em>, <em>DGKI, MEF2C, MAB21L2, MYL7</em>, <em>LDB3</em>, <em>SLC7A11,</em> and <em>CALD1</em>. Predictive models developed from these genes provide high accuracy in determining terminal CM purities at the CPC stage. Further, insights into mechanisms of batch failure and dominant non-CM cell types generated in failed batches are elucidated. Namely EMT, MAPK, and WNT signaling emerge as significant drivers of batch divergence, giving rise to off-target populations of fibroblasts/mural cells, skeletal myocytes, epicardial cells, and a non-CPC SLC7A11+ subpopulation. This study demonstrates how integrated multi-omic analysis of progenitor cells can identify quality attributes of that progenitor and predict differentiation outcomes, thereby improving differentiation protocols and increasing process robustness.</p></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"196 ","pages":"Pages 52-70"},"PeriodicalIF":4.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120063","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":"Endogenous complement 1q binding protein (C1qbp) regulates mitochondrial permeability transition and post-myocardial infarction remodeling and dysfunction","authors":"Manuel Gutiérrez-Aguilar ,&nbsp;Paula J. Klutho ,&nbsp;Rodrigo Aguayo-Ortiz ,&nbsp;Lihui Song ,&nbsp;Christopher P. Baines","doi":"10.1016/j.yjmcc.2024.08.005","DOIUrl":"10.1016/j.yjmcc.2024.08.005","url":null,"abstract":"<div><p>The mitochondrial permeability transition (MPT) pore regulates necrotic cell death following diverse cardiac insults. While the componentry of the pore itself remains controversial, Cyclophilin D (CypD) has been well-established as a positive regulator of pore opening. We have previously identified Complement 1q-binding protein (C1qbp) as a novel CypD-interacting molecule and a negative regulator of MPT-dependent cell death <em>in vitro.</em> However, its effects on the MPT pore and sensitivity to cell death in the heart remain untested. We therefore hypothesized that C1qbp would inhibit MPT in cardiac mitochondria and protect cardiac myocytes against cell death <em>in vivo</em>. To investigate the effects of C1qbp in the myocardium we generated gain- and loss-of-function mice. Transgenic C1qbp overexpression resulted in decreased complex protein expression and reduced mitochondrial respiration and ATP production but MPT was unaffected. In contrast, while <em>C1qbp</em>^+/− mice did not exhibit any changes in mitochondrial protein expression, respiration, or ATP, the MPT pore was markedly sensitized to Ca²⁺ in these animals. Neither overexpression nor depletion of C1qbp significantly affected baseline heart morphology or function at 3 months of age. When subjected to myocardial infarction, C1qbp transgenic mice exhibited similar infarct sizes and cardiac remodeling to non-transgenic mice, consistent with the lack of an effect on MPT. In contrast, cardiac scar formation and dysfunction were significantly increased in the <em>C1qbp</em>^+/− mice compared to <em>C1qbp</em>^+/+ controls. Our results suggest that C1qbp is required for normal regulation of the MPT pore and mitochondrial function, and influences cardiac remodeling following MI, the latter more likely being independent of C1qbp effects on the MPT pore.</p></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"196 ","pages":"Pages 1-11"},"PeriodicalIF":4.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108274","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":"Cardiac fat adipocytes: An optimized protocol for isolation of ready-to-use mature adipocytes from human pericardial adipose tissue","authors":"Stefano Quarta ,&nbsp;Giuseppe Santarpino ,&nbsp;Maria Annunziata Carluccio ,&nbsp;Nadia Calabriso ,&nbsp;Francesco Cardetta ,&nbsp;Laura Siracusa ,&nbsp;Tonia Strano ,&nbsp;Ilaria Palamà ,&nbsp;Gabriella Leccese ,&nbsp;Francesco Visioli ,&nbsp;Marika Massaro","doi":"10.1016/j.yjmcc.2024.08.006","DOIUrl":"10.1016/j.yjmcc.2024.08.006","url":null,"abstract":"<div><p>A better understanding of the pathophysiology of cardiac fat depots is crucial to describe their role in the development of cardiovascular diseases. To this end, we have developed a method to isolate mature fat cells from the pericardial adipose tissue (PAT), the most accessible cardiac fat depot during cardiac surgery. Using enzymatic isolation, we were able to successfully obtain mature fat cells together with the corresponding cells of the stromal vascular fraction (SVF). We subjected the PAT adipocytes to thorough morphological and molecular characterization, including detailed fatty acid profiling, and simultaneously investigated their reactivity to external stimuli. Our approach resulted in highly purified fat cells with sustained viability for up to 72 h after explantation. Remarkably, these adipocytes responded to multiple challenges, including pro-inflammatory and metabolic stimuli, indicating their potential to trigger a pro-inflammatory response and modulate endothelial cell behavior. Furthermore, we have created conditions to maintain whole PAT in culture and preserve their viability and reactivity to external stimuli. The efficiency of cell recovery combined with minimal dedifferentiation underscores the promise for future applications as a personalized tool for screening and assessing individual patient responses to drugs and supplements or nutraceuticals.</p></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"196 ","pages":"Pages 12-25"},"PeriodicalIF":4.9,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108273","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":"Metabolic cycles: A unifying concept for energy transfer in the heart","authors":"Mitchell Beito ,&nbsp;Heinrich Taegtmeyer","doi":"10.1016/j.yjmcc.2024.08.002","DOIUrl":"10.1016/j.yjmcc.2024.08.002","url":null,"abstract":"<div><p>It is still debated whether changes in metabolic flux are cause or consequence of contractile dysfunction in non-ischemic heart disease. We have previously proposed a model of cardiac metabolism grounded in a series of six moiety-conserved, interconnected cycles. In view of a recent interest to augment oxygen availability in heart failure through iron supplementation, we integrated this intervention in terms of moiety conservation. Examining published work from both human and murine models, we argue this strategy restores a mitochondrial cycle of energy transfer by enhancing mitochondrial pyruvate carrier (MPC) expression and providing pyruvate as a substrate for carboxylation and anaplerosis. Metabolomic data from failing heart muscle reveal elevated pyruvate levels with a concomitant decrease in the levels of Krebs cycle intermediates. Additionally, MPC is downregulated in the same failing hearts, as well as under hypoxic conditions. MPC expression increases upon mechanical unloading in the failing human heart, as does contractile function. We note that MPC deficiency also alters expression of enzymes involved in pyruvate carboxylation and decarboxylation, increases intermediates of biosynthetic pathways, and eventually leads to cardiac hypertrophy and dilated cardiomyopathy. Collectively, we propose that an unbroken chain of moiety-conserved cycles facilitates energy transfer in the heart. We refer to the transport and subsequent carboxylation of pyruvate in the mitochondrial matrix as an example and a proposed target for metabolic support to reverse impaired contractile function.</p></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"195 ","pages":"Pages 103-109"},"PeriodicalIF":4.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000164","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":"Vascular endothelium: The interface for multiplex signal transduction","authors":"Chak Kwong Cheng,&nbsp;Yu Huang","doi":"10.1016/j.yjmcc.2024.08.004","DOIUrl":"10.1016/j.yjmcc.2024.08.004","url":null,"abstract":"<div><p>As the innermost monolayer of the vasculature, endothelial cells (ECs) serve as the interface for multiplex signal transduction. Directly exposed to blood-borne factors, both endogenous and exogenous, ECs actively mediate vascular homeostasis and represent a therapeutic target against cardiometabolic diseases. ECs act as the first-line gateway between gut-derived substances and vasculature. Additionally, ECs convert blood flow-exerted hemodynamic forces into downstream biochemical signaling to modulate vascular pathophysiology. Besides, ECs can sense other forms of stimuli, like cell extrusion, thermal stimulation, photostimulation, radiation, magnetic field, noise, and gravity. Future efforts are still needed to deepen our understanding on endothelial biology.</p></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"195 ","pages":"Pages 97-102"},"PeriodicalIF":4.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988176","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":"Mechanisms of the septic heart: From inflammatory response to myocardial edema","authors":"Dihan Fan ,&nbsp;Rongxue Wu","doi":"10.1016/j.yjmcc.2024.08.003","DOIUrl":"10.1016/j.yjmcc.2024.08.003","url":null,"abstract":"<div><p>Sepsis-induced myocardial dysfunction (SIMD), also known as sepsis-induced cardiomyopathy (SICM), is linked to significantly increased mortality. Despite its clinical importance, effective therapies for SIMD remain elusive, largely due to an incomplete understanding of its pathogenesis. Over the past five decades, research involving both animal models and human studies has highlighted several pathogenic mechanisms of SICM, yet many aspects remain unexplored. Initially thought to be primarily driven by inflammatory cytokines, current research indicates that these alone are insufficient for the development of cardiac dysfunction. Recent studies have brought attention to additional mechanisms, including excessive nitric oxide production, mitochondrial dysfunction, and disturbances in calcium homeostasis, as contributing factors in SICM. Emerging clinical evidence has highlighted the significant role of myocardial edema in the pathogenesis of SICM, particularly its association with cardiac remodeling in septic shock patients. This review synthesizes our current understanding of SIMD/SICM, focusing on myocardial edema's contribution to cardiac dysfunction and the critical role of the bradykinin receptor B1 (B1R) in altering myocardial microvascular permeability, a potential key player in myocardial edema development during sepsis. Additionally, this review briefly summarizes existing therapeutic strategies and their challenges and explores future research directions. It emphasizes the need for a deeper understanding of SICM to develop more effective treatments.</p></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"195 ","pages":"Pages 73-82"},"PeriodicalIF":4.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982534","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":"Suppression of autophagy induces senescence in the heart","authors":"Peiyong Zhai,&nbsp;Eun-Ah Sung,&nbsp;Yuka Shiheido-Watanabe,&nbsp;Koichiro Takayama,&nbsp;Yimin Tian,&nbsp;Junichi Sadoshima","doi":"10.1016/j.yjmcc.2024.08.001","DOIUrl":"10.1016/j.yjmcc.2024.08.001","url":null,"abstract":"<div><p>Aging is a critical risk factor for heart disease, including ischemic heart disease and heart failure. Cellular senescence, characterized by DNA damage, resistance to apoptosis and the senescence-associated secretory phenotype (SASP), occurs in many cell types, including cardiomyocytes. Senescence precipitates the aging process in surrounding cells and the organ through paracrine mechanisms. Generalized autophagy, which degrades cytosolic materials in a non-selective manner, is decreased during aging in the heart. This decrease causes deterioration of cellular quality control mechanisms, facilitates aging and negatively affects lifespan in animals, including mice. Although suppression of generalized autophagy could promote senescence, it remains unclear whether the suppression of autophagy directly stimulates senescence in cardiomyocytes, which, in turn, promotes myocardial dysfunction in the heart. We addressed this question using mouse models with a loss of autophagy function. Suppression of general autophagy in cardiac-specific <em>Atg7</em> knockout (<em>Atg7</em>cKO) mice caused accumulation of senescent cardiomyocytes. Induction of senescence <em>via</em> downregulation of <em>Atg7</em> was also observed in chimeric <em>Atg7</em> cardiac-specific KO mice and cultured cardiomyocytes <em>in vitro</em>, suggesting that the effect of autophagy suppression upon induction of senescence is cell autonomous. ABT-263, a senolytic agent, reduced the number of senescent myocytes and improved cardiac function in <em>Atg7</em>cKO mice. Suppression of autophagy and induction of senescence were also observed in doxorubicin-treated hearts, where reactivation of autophagy alleviated senescence in cardiomyocytes and cardiac dysfunction. These results suggest that suppression of general autophagy directly induces senescence in cardiomyocytes, which in turn promotes cardiac dysfunction.</p></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"195 ","pages":"Pages 83-96"},"PeriodicalIF":4.9,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0022282824001287/pdfft?md5=b380ca83875f8fd7a8252e530ed3f75c&pid=1-s2.0-S0022282824001287-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906822","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}

{"title":"NAD metabolism and heart failure: Mechanisms and therapeutic potentials","authors":"Matthew A. Walker,&nbsp;Rong Tian","doi":"10.1016/j.yjmcc.2024.07.008","DOIUrl":"10.1016/j.yjmcc.2024.07.008","url":null,"abstract":"<div><p>Nicotinamide adenine dinucleotide provides the critical redox pair, NAD⁺ and NADH, for cellular energy metabolism. In addition, NAD⁺ is the precursor for de novo NADP⁺ synthesis as well as the co-substrates for CD38, poly(ADP-ribose) polymerase and sirtuins, thus, playing a central role in the regulation of oxidative stress and cell signaling. Declines of the NAD⁺ level and altered NAD⁺/NADH redox states have been observed in cardiometabolic diseases of various etiologies. NAD based therapies have emerged as a promising strategy to treat cardiovascular disease. Strategies that reduce NAD⁺ consumption or promote NAD⁺ production have repleted intracellular NAD⁺ or normalized NAD⁺/NADH redox in preclinical studies. These interventions have shown cardioprotective effects in multiple models suggesting a great promise of the NAD⁺ elevating therapy. Mechanisms for the benefit of boosting NAD⁺ level, however, remain incompletely understood. Moreover, despite the robust pre-clinical studies there are still challenges to translate the therapy to clinic. Here, we review the most up to date literature on mechanisms underlying the NAD⁺ elevating interventions and discuss the progress of human studies. We also aim to provide a better understanding of how NAD metabolism is changed in failing hearts with a particular emphasis on types of strategies employed and methods to target these pathways. Finally, we conclude with a comprehensive assessment of the challenges in developing NAD-based therapies for heart diseases, and to provide a perspective on the future of the targeting strategies.</p></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"195 ","pages":"Pages 45-54"},"PeriodicalIF":4.9,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889479","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":"Oncoprotein-induced transcript 3 protein-enriched extracellular vesicles promotes NLRP3 ubiquitination to alleviate acute lung injury after cardiac surgery","authors":"Yan Li ,&nbsp;Ya-Ting Chen ,&nbsp;Jia-Sheng Liu ,&nbsp;Kai-Feng Liang ,&nbsp;Yuan-Kai Song ,&nbsp;Yang Cao ,&nbsp;Cai-Yun Chen ,&nbsp;Yu-Peng Jian ,&nbsp;Xiao-Jun Liu ,&nbsp;Ying-Qi Xu ,&nbsp;Hao-Xiang Yuan ,&nbsp;Zhi-Jun Ou ,&nbsp;Jing-Song Ou","doi":"10.1016/j.yjmcc.2024.07.011","DOIUrl":"10.1016/j.yjmcc.2024.07.011","url":null,"abstract":"<div><p>Acute lung injury (ALI) including acute respiratory distress syndrome (ARDS) is a major complication and increase the mortality of patients with cardiac surgery. We previously found that the protein cargoes enriched in circulating extracellular vesicles (EVs) are closely associated with cardiopulmonary disease. We aimed to evaluate the implication of EVs on cardiac surgery-associated ALI/ARDS. The correlations between “oncoprotein-induced transcript 3 protein (OIT3) positive” circulating EVs and postoperative ARDS were assessed. The effects of OIT3-overexpressed EVs on the cardiopulmonary bypass (CPB) -induced ALI <em>in vivo</em> and inflammation of human bronchial epithelial cells (BEAS-2B) were detected. OIT3 enriched in circulating EVs is reduced after cardiac surgery with CPB, especially with postoperative ARDS. The “OIT3 positive” EVs negatively correlate with lung edema, hypoxemia and CPB time. The OIT3-overexpressed EVs can be absorbed by pulmonary epithelial cells and OIT3 transferred by EVs triggered K48- and K63-linked polyubiquitination to inactivate NOD-like receptor protein 3 (NLRP3) inflammasome, and restrains pro-inflammatory cytokines releasing and immune cells infiltration in lung tissues, contributing to the alleviation of CPB-induced ALI. Overexpression of OIT3 in human bronchial epithelial cells have similar results. OIT3 promotes the E3 ligase Cbl proto-oncogene B associated with NLRP3 to induce the ubiquitination of NLRP3. Immunofluorescence tests reveal that OIT3 is reduced in the generation from the liver sinusoids endothelial cells (LSECs) and secretion in liver-derived EVs after CPB. In conclusion, OIT3 enriched in EVs is a promising biomarker of postoperative ARDS and a therapeutic target for ALI after cardiac surgery.</p></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"195 ","pages":"Pages 55-67"},"PeriodicalIF":4.9,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875093","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}