Clinical science最新文献_第9页

Hallmarks of ageing in human skeletal muscle and implications for understanding the pathophysiology of sarcopenia in women and men. 人类骨骼肌衰老的标志及其对理解男女肌肉减少症病理生理学的意义。

IF 6 2区医学

Clinical science Pub Date : 2023-11-29 DOI: 10.1042/CS20230319

Antoneta Granic, Karen Suetterlin, Tea Shavlakadze, Miranda D Grounds, Avan A Sayer

{"title":"Hallmarks of ageing in human skeletal muscle and implications for understanding the pathophysiology of sarcopenia in women and men.","authors":"Antoneta Granic, Karen Suetterlin, Tea Shavlakadze, Miranda D Grounds, Avan A Sayer","doi":"10.1042/CS20230319","DOIUrl":"10.1042/CS20230319","url":null,"abstract":"Ageing is a complex biological process associated with increased morbidity and mortality. Nine classic, interdependent hallmarks of ageing have been proposed involving genetic and biochemical pathways that collectively influence ageing trajectories and susceptibility to pathology in humans. Ageing skeletal muscle undergoes profound morphological and physiological changes associated with loss of strength, mass, and function, a condition known as sarcopenia. The aetiology of sarcopenia is complex and whilst research in this area is growing rapidly, there is a relative paucity of human studies, particularly in older women. Here, we evaluate how the nine classic hallmarks of ageing: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication contribute to skeletal muscle ageing and the pathophysiology of sarcopenia. We also highlight five novel hallmarks of particular significance to skeletal muscle ageing: inflammation, neural dysfunction, extracellular matrix dysfunction, reduced vascular perfusion, and ionic dyshomeostasis, and discuss how the classic and novel hallmarks are interconnected. Their clinical relevance and translational potential are also considered.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"137 22","pages":"1721-1751"},"PeriodicalIF":6.0,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10665130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138175823","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}

引用次数: 0

PE (0:0/14:0), an endogenous metabolite of the gut microbiota, exerts protective effects against sepsis-induced intestinal injury by modulating the AHR/CYP1A1 pathway. PE（0:0/14:0）是肠道微生物群的内源性代谢产物，通过调节AhR/CYP1A1途径对败血症诱导的肠道损伤发挥保护作用。

IF 6 2区医学

Clinical science Pub Date : 2023-11-29 DOI: 10.1042/CS20230704

Wang Ze Tian, Qi Yue, Wang Fei, Peng Zi Yao, Rui Qin Han, Jianguo Tang

{"title":"PE (0:0/14:0), an endogenous metabolite of the gut microbiota, exerts protective effects against sepsis-induced intestinal injury by modulating the AHR/CYP1A1 pathway.","authors":"Wang Ze Tian, Qi Yue, Wang Fei, Peng Zi Yao, Rui Qin Han, Jianguo Tang","doi":"10.1042/CS20230704","DOIUrl":"10.1042/CS20230704","url":null,"abstract":"Sepsis is known to cause damage to the intestinal mucosa, leading to bacterial translocation, and exacerbation of both local and remote organ impairments. In the present study, fecal samples were collected from both septic and healthy individuals. Analysis through 16s rRNA sequencing of the fecal microbiota revealed that sepsis disrupts the balance of the gut microbial community. Recent research has highlighted the association of lipid metabolism with disease. By analyzing the fecal metabolome, four lipid metabolites that showed significant differences between the two groups were identified: PE (O-16:0/0:0), PE (17:0/0:0), PE (0:0/14:0), and PE (12:0/20:5 (5Z, 8Z, 11Z, 14Z, 17Z)). Notably, the serum levels of PE (0:0/14:0) were higher in the healthy group. Subsequent in vitro and in vivo experiments demonstrated the protective effects of this compound against sepsis-induced intestinal barrier damage. Label-free proteomic analysis showed significant differences in the expression levels of the aryl hydrocarbon receptor (AHR), a protein implicated in sepsis pathogenesis, between the LPS-Caco-2 and LPS-Caco-2 + PE (0:0/14:0) groups. Further analysis, with the help of Discovery Studio 3.5 software and co-immunoprecipitation assays, confirmed the direct interaction between AHR and PE (0:0/14:0). In the cecal ligation and puncture (CLP) model, treatment with PE (0:0 /14:0) was found to up-regulate the expression of tight junction proteins through the AHR/Cytochrome P450, family 1, subfamily A, and polypeptide 1 (CYP1A1) pathway. This highlights the potential therapeutic use of PE (0:0/14:0) in addressing sepsis-induced intestinal barrier damage.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1753-1769"},"PeriodicalIF":6.0,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421390","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}

引用次数: 0

Endothelial progenitor cells in pregnancy-related diseases. 内皮祖细胞在妊娠相关疾病中的作用

IF 6 2区医学

Clinical science Pub Date : 2023-11-29 DOI: 10.1042/CS20230853

Yangyang Chen, Gui Wan, Zeyun Li, Xiaoxia Liu, Yin Zhao, Li Zou, Weifang Liu

引用次数: 0

Gut microbiota depletion aggravates bile acid-induced liver pathology in mice with a human-like bile acid composition. 肠道微生物群耗竭加重了具有类人胆汁酸成分的小鼠胆汁酸诱导的肝脏病理。

IF 6 2区医学

Clinical science Pub Date : 2023-11-15 DOI: 10.1042/CS20230812

Esther Verkade, Wenqiang Shen, Milaine V Hovingh, Niels L Mulder, Krisztina de Bruyn, Martijn Koehorst, Hilde D de Vries, Vincent W Bloks, Folkert Kuipers, Jan Freark de Boer

{"title":"Gut microbiota depletion aggravates bile acid-induced liver pathology in mice with a human-like bile acid composition.","authors":"Esther Verkade, Wenqiang Shen, Milaine V Hovingh, Niels L Mulder, Krisztina de Bruyn, Martijn Koehorst, Hilde D de Vries, Vincent W Bloks, Folkert Kuipers, Jan Freark de Boer","doi":"10.1042/CS20230812","DOIUrl":"10.1042/CS20230812","url":null,"abstract":"Cyp2c70-deficient mice have a human-like bile acid (BA) composition due to their inability to convert chenodeoxycholic acid (CDCA) into rodent-specific muricholic acids (MCAs). However, the hydrophobic BA composition in these animals is associated with liver pathology. Although Cyp2c70-ablation has been shown to alter gut microbiome composition, the impact of gut bacteria on liver pathology in Cyp2c70-/- mice remains to be established. Therefore, we treated young-adult male and female wild-type (WT) and Cyp2c70-/- mice with antibiotics (AB) with broad specificity to deplete the gut microbiota and assessed the consequences on BA metabolism and liver pathology. Female Cyp2c70-/- mice did not tolerate AB treatment, necessitating premature termination of the experiment. Male Cyp2c70-/- mice did tolerate AB but showed markedly augmented liver pathology after 6 weeks of treatment. Dramatic downregulation of hepatic Cyp8b1 expression (-99%) caused a reduction in the proportions of 12α-hydroxylated BAs in the circulating BA pools of AB-treated male Cyp2c70-/- mice. Interestingly, the resulting increased BA hydrophobicity strongly correlated with various indicators of liver pathology. Moreover, genetic inactivation of Cyp8b1 in livers of male Cyp2c70-/- mice increased liver pathology, while addition of ursodeoxycholic acid to the diet prevented weight loss and liver pathology in AB-treated female Cyp2c70-/- mice. In conclusion, depletion of gut microbiota in Cyp2c70-/- mice aggravates liver pathology at least in part by increasing the hydrophobicity of the circulating BA pool. These findings highlight that the potential implications of AB administration to cholestatic patients should be evaluated in a systematic manner.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1637-1650"},"PeriodicalIF":6.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421389","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}

引用次数: 0

USP38 regulates inflammatory cardiac remodeling after myocardial infarction. USP38调节心肌梗死后炎症性心脏重塑。

IF 6 2区医学

Clinical science Pub Date : 2023-11-15 DOI: 10.1042/CS20230728

Yang Gong, Bin Kong, Wei Shuai, Tao Chen, Jing Jing Zhang, He Huang

{"title":"USP38 regulates inflammatory cardiac remodeling after myocardial infarction.","authors":"Yang Gong, Bin Kong, Wei Shuai, Tao Chen, Jing Jing Zhang, He Huang","doi":"10.1042/CS20230728","DOIUrl":"10.1042/CS20230728","url":null,"abstract":"Background: The inflammatory response and subsequent ventricular remodeling are key factors contributing to ventricular arrhythmias (VAs) after myocardial infarction (MI). Ubiquitin-specific protease 38 (USP38) is a member of the USP family, but the impact of USP38 in arrhythmia substrate generation after MI remains unclear. This study aimed to determine the role of USP38 in post-MI VAs and its underlying mechanisms.Methods and results: Surgical left descending coronary artery ligation was used to construct MI models. Morphological, biochemical, histological, and electrophysiological studies and molecular analyses were performed after MI on days 3 and 28. We found that the USP38 expression was remarkably increased after MI. Cardiac-conditional USP38 knockout (USP38-CKO) reduces the expression of the inflammatory marker CD68 as well as the inflammatory factors TNF-α and IL-1β after MI, thereby alleviating advanced cardiac fibrosis, electrical remodeling, ion channel remodeling, and susceptibility to VAs. In contrast, cardiac-specific USP38 overexpression (USP38-TG) showed a significant opposite effect, exacerbating the early inflammatory response and cardiac remodeling after MI. Mechanistically, USP38 knockout inhibited activation of the TAK1/NF-κB signaling pathway after MI, whereas USP38 overexpression enhanced activation of the TAK1/NF-κB signaling pathway after MI.Conclusions: Our study confirms that USP38-CKO attenuates the inflammatory response, improves ventricular remodeling after myocardial infarction, and reduces susceptibility to malignant VA by inhibiting the activation of the TAK1/NF-κB pathway, with USP38-TG playing an opposing role. These results suggest that USP38 may be an important target for the treatment of cardiac remodeling and arrhythmias after MI.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1665-1681"},"PeriodicalIF":6.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71410997","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}

引用次数: 0

Overexpression of the LAT1 in primary human trophoblast cells increases the uptake of essential amino acids and activates mTOR signaling. LAT1在原代人类滋养层细胞中的过表达增加了必需氨基酸的摄取并激活mTOR信号传导。

IF 6 2区医学

Clinical science Pub Date : 2023-11-15 DOI: 10.1042/CS20230490

Fredrick J Rosario, Johann Urschitz, Theresa L Powell, Thomas L Brown, Thomas Jansson

{"title":"Overexpression of the LAT1 in primary human trophoblast cells increases the uptake of essential amino acids and activates mTOR signaling.","authors":"Fredrick J Rosario, Johann Urschitz, Theresa L Powell, Thomas L Brown, Thomas Jansson","doi":"10.1042/CS20230490","DOIUrl":"10.1042/CS20230490","url":null,"abstract":"The System L amino acid transporter, particularly the isoform Large Neutral Amino Acid Transporter Small Subunit 1 (LAT1) encoded by SLC7A5, is believed to mediate the transfer of essential amino acids in the human placenta. Placental System L amino acid transporter expression and activity is decreased in pregnancies complicated by IUGR and increased in fetal overgrowth. However, it remains unknown if changes in the expression of LAT1 are mechanistically linked to System L amino acid transport activity. Here, we combined overexpression approaches with protein analysis and functional studies in cultured primary human trophoblast (PHT) cells to test the hypothesis that SLC7A5 overexpression increases the uptake of essential amino acids and activates mTOR signaling in PHT cells. Overexpression of SLC7A5 resulted in a marked increase in protein expression of LAT1 in the PHT cells microvillous plasma membrane and System L amino acid transporter activity. Moreover, mTOR signaling was activated, and System A amino acid transporter activity increased following SLC7A5 overexpression, suggesting coordination of trophoblast amino transporter expression and activity to ensure balanced nutrient flux to the fetus. This is the first report showing that overexpression of LAT1 is sufficient to increase the uptake of essential amino acids in PHT cells, which activates mTOR, a master regulator of placental function. The decreased placental System L activity in human IUGR and the increased placental activity of this transporter system in some cases of fetal overgrowth may directly contribute to changes in fetal amino acid availability and altered fetal growth in these pregnancy complications.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1651-1664"},"PeriodicalIF":6.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49675098","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}

引用次数: 0

A normative microbiome is not restored following kidney transplantation. 肾移植后不能恢复正常的微生物组。

IF 6 2区医学

Clinical science Pub Date : 2023-10-31 DOI: 10.1042/CS20230779

Hannah Craven, Helen Erlandsson, Dagmara McGuiness, David McGuiness, Denise Mafra, Umer Ijaz, Peter Bergman, Paul G Shiels, Peter Stenvinkel

{"title":"A normative microbiome is not restored following kidney transplantation.","authors":"Hannah Craven, Helen Erlandsson, Dagmara McGuiness, David McGuiness, Denise Mafra, Umer Ijaz, Peter Bergman, Paul G Shiels, Peter Stenvinkel","doi":"10.1042/CS20230779","DOIUrl":"10.1042/CS20230779","url":null,"abstract":"Dialysis and kidney transplantation (Ktx) mitigate some of the physiological deficits in chronic kidney disease (CKD), but it remains to be determined if these mitigate microbial dysbiosis and the production of inflammatory microbial metabolites, which contribute significantly to the uraemic phenotype. We have investigated bacterial DNA signatures present in the circulation of CKD patients and those receiving a KTx. Our data are consistent with increasing dysbiosis as CKD progresses, with an accompanying increase in trimethylamine (TMA) producing pathobionts Pseudomonas and Bacillus. Notably, KTx patients displayed a significantly different microbiota compared with CKD5 patients, which surprisingly included further increase in TMA producing Bacillus and loss of salutogenic Lactobacilli. Only two genera (Viellonella and Saccharimonidales) showed significant differences in abundance following KTx that may reflect a reciprocal relationship between TMA producers and utilisers, which supersedes restoration of a normative microbiome. Our metadata analysis confirmed that TMA N-oxide (TMAO) along with one carbon metabolism had significant impact upon both inflammatory burden and the composition of the microbiome. This indicates that these metabolites are key to shaping the uraemic microbiome and might be exploited in the development of dietary intervention strategies to both mitigate the physiological deficits in CKD and enable the restoration of a more salutogenic microbiome.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1563-1575"},"PeriodicalIF":6.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10582644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41142842","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}

引用次数: 0

Adverse effects of ovarian cryopreservation and auto-transplantation on ovarian grafts and quality of produced oocytes in a mouse model. 卵巢冷冻保存和自体移植对小鼠模型中卵巢移植物和卵母细胞质量的不良影响。

IF 6 2区医学

Clinical science Pub Date : 2023-10-31 DOI: 10.1042/CS20230483

Que Wu, Gaizhen Ru, Wanfen Xiao, Qian Wang, Zhiling Li

{"title":"Adverse effects of ovarian cryopreservation and auto-transplantation on ovarian grafts and quality of produced oocytes in a mouse model.","authors":"Que Wu, Gaizhen Ru, Wanfen Xiao, Qian Wang, Zhiling Li","doi":"10.1042/CS20230483","DOIUrl":"10.1042/CS20230483","url":null,"abstract":"The process of ovarian cryopreservation and transplantation is the only feasible fertility preservation method for prepubertal girls and female patients with cancer who cannot delay radiotherapy and chemotherapy. However, basic research on this technique is lacking. To better understand ovarian function and oocyte quality after ovarian tissue (OT) transplantation, we characterised the appearance, angiogenesis, and endocrine function of ovarian grafts in a murine model; the mitochondrial function and DNA damage in oocytes isolated from the OT; and the development of embryos after in vitro fertilisation. The results showed a decrease in oocyte numbers in the transplanted OT, abnormal endocrine function of ovarian grafts, as well as dysfunctional mitochondria and DNA damage in the oocytes, which could adversely affect subsequent embryonic development. However, these adverse phenotypes were partially or completely resolved within 21 days of transplantation, suggesting that ovulation induction and assisted pregnancy treatment should not be conducted too soon after OT transfer to ensure optimal patient and offspring outcomes.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1577-1591"},"PeriodicalIF":6.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10600147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41113130","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}

引用次数: 0

High-fructose corn syrup aggravates colitis via microbiota dysbiosis-mediated Th17/Treg imbalance. 高果糖玉米糖浆通过微生物群失调介导的Th17/Treg失衡加重结肠炎。

IF 6 2区医学

Clinical science Pub Date : 2023-10-31 DOI: 10.1042/CS20230788

Mingxia Zhou, Xiaoman Liu, Jing He, Xinyu Xu, Chenxi Ju, Shangjian Luo, Xiajuan Lu, Peng Du, Yingwei Chen

{"title":"High-fructose corn syrup aggravates colitis via microbiota dysbiosis-mediated Th17/Treg imbalance.","authors":"Mingxia Zhou, Xiaoman Liu, Jing He, Xinyu Xu, Chenxi Ju, Shangjian Luo, Xiajuan Lu, Peng Du, Yingwei Chen","doi":"10.1042/CS20230788","DOIUrl":"10.1042/CS20230788","url":null,"abstract":"Dietary fructose is widely used in beverages, processed foods, and Western diets as food additives, and is closely related to the increased prevalence of multiple diseases, including inflammatory bowel disease (IBD). However, the detailed mechanism by which high fructose disrupts intestinal homeostasis remains elusive. The present study showed that high-fructose corn syrup (HFCS) administration exacerbated intestinal inflammation and deteriorated barrier integrity. Several in vivo experimental models were utilized to verify the importance of gut microbiota and immune cells in HFCS-mediated dextran sulfate sodium (DSS)-induced colitis. In addition, untargeted metabolomics analysis revealed the imbalance between primary bile acids (PBAs) and secondary bile acids (SBAs) in feces. Hence, high fructose was speculated to modulate gut microbiota community and reduced the relative abundance of Clostridium and Clostridium scindens at genus and species level respectively, followed by a decrease in SBAs, especially isoalloLCA, thereby affecting Th17/Treg cells equilibrium and promoting intestinal inflammation. These findings provide novel insights into the crosstalk between gut flora, bile acids, and mucosal immunity, and highlight potential strategies for precise treatment of IBD.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1619-1635"},"PeriodicalIF":6.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41193759","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}

引用次数: 0

The vascular Na,K-ATPase: clinical implications in stroke, migraine, and hypertension. 血管Na, k - atp酶:卒中，偏头痛和高血压的临床意义。

IF 6 2区医学

Clinical science Pub Date : 2023-10-31 DOI: 10.1042/CS20220796

Christian Staehr, Christian Aalkjaer, Vladimir V Matchkov

{"title":"The vascular Na,K-ATPase: clinical implications in stroke, migraine, and hypertension.","authors":"Christian Staehr, Christian Aalkjaer, Vladimir V Matchkov","doi":"10.1042/CS20220796","DOIUrl":"10.1042/CS20220796","url":null,"abstract":"In the vascular wall, the Na,K-ATPase plays an important role in the control of arterial tone. Through cSrc signaling, it contributes to the modulation of Ca2+ sensitivity in vascular smooth muscle cells. This review focuses on the potential implication of Na,K-ATPase-dependent intracellular signaling pathways in severe vascular disorders; ischemic stroke, familial migraine, and arterial hypertension. We propose similarity in the detrimental Na,K-ATPase-dependent signaling seen in these pathological conditions. The review includes a retrospective proteomics analysis investigating temporal changes after ischemic stroke. The analysis revealed that the expression of Na,K-ATPase α isoforms is down-regulated in the days and weeks following reperfusion, while downstream Na,K-ATPase-dependent cSrc kinase is up-regulated. These results are important since previous studies have linked the Na,K-ATPase-dependent cSrc signaling to futile recanalization and vasospasm after stroke. The review also explores a link between the Na,K-ATPase and migraine with aura, as reduced expression or pharmacological inhibition of the Na,K-ATPase leads to cSrc kinase signaling up-regulation and cerebral hypoperfusion. The review discusses the role of an endogenous cardiotonic steroid-like compound, ouabain, which binds to the Na,K-ATPase and initiates the intracellular cSrc signaling, in the pathophysiology of arterial hypertension. Currently, our understanding of the precise control mechanisms governing the Na,K-ATPase/cSrc kinase regulation in the vascular wall is limited. Understanding the role of vascular Na,K-ATPase signaling is essential for developing targeted treatments for cerebrovascular disorders and hypertension, as the Na,K-ATPase is implicated in the pathogenesis of these conditions and may contribute to their comorbidity.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"137 20","pages":"1595-1618"},"PeriodicalIF":6.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0e/eb/cs-137-cs20220796.PMC10600256.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50157238","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}

引用次数: 1