Physiological reviews最新文献

{"title":"Multiscale structure and function of the aortic valve apparatus.","authors":"Hussam El-Nashar, Malak Sabry, Yuan-Tsan Tseng, Nadine Francis, Najma Latif, Kim H Parker, James E Moore, Magdi H Yacoub","doi":"10.1152/physrev.00038.2022","DOIUrl":"10.1152/physrev.00038.2022","url":null,"abstract":"<p><p>Whereas studying the aortic valve in isolation has facilitated the development of life-saving procedures and technologies, the dynamic interplay of the aortic valve and its surrounding structures is vital to preserving their function across the wide range of conditions encountered in an active lifestyle. Our view is that these structures should be viewed as an integrated functional unit, here referred to as the aortic valve apparatus (AVA). The coupling of the aortic valve and root, left ventricular outflow tract, and blood circulation is crucial for AVA's functions: unidirectional flow out of the left ventricle, coronary perfusion, reservoir function, and support of left ventricular function. In this review, we explore the multiscale biological and physical phenomena that underlie the simultaneous fulfillment of these functions. A brief overview of the tools used to investigate the AVA, such as medical imaging modalities, experimental methods, and computational modeling, specifically fluid-structure interaction (FSI) simulations, is included. Some pathologies affecting the AVA are explored, and insights are provided on treatments and interventions that aim to maintain quality of life. The concepts explained in this article support the idea of AVA being an integrated functional unit and help identify unanswered research questions. Incorporating phenomena through the molecular, micro, meso, and whole tissue scales is crucial for understanding the sophisticated normal functions and diseases of the AVA.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1487-1532"},"PeriodicalIF":29.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41145423","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":"Mesenchymal stromal cells for improvement of cardiac function following acute myocardial infarction: a matter of timing.","authors":"Stéphanie Barrère-Lemaire, Anne Vincent, Christian Jorgensen, Christophe Piot, Joël Nargeot, Farida Djouad","doi":"10.1152/physrev.00009.2023","DOIUrl":"10.1152/physrev.00009.2023","url":null,"abstract":"<p><p>Acute myocardial infarction (AMI) is the leading cause of cardiovascular death and remains the most common cause of heart failure. Reopening of the occluded artery, i.e., reperfusion, is the only way to save the myocardium. However, the expected benefits of reducing infarct size are disappointing due to the reperfusion paradox, which also induces specific cell death. These ischemia-reperfusion (I/R) lesions can account for up to 50% of final infarct size, a major determinant for both mortality and the risk of heart failure (morbidity). In this review, we provide a detailed description of the cell death and inflammation mechanisms as features of I/R injury and cardioprotective strategies such as ischemic postconditioning as well as their underlying mechanisms. Due to their biological properties, the use of mesenchymal stromal/stem cells (MSCs) has been considered a potential therapeutic approach in AMI. Despite promising results and evidence of safety in preclinical studies using MSCs, the effects reported in clinical trials are not conclusive and even inconsistent. These discrepancies were attributed to many parameters such as donor age, in vitro culture, and storage time as well as injection time window after AMI, which alter MSC therapeutic properties. In the context of AMI, future directions will be to generate MSCs with enhanced properties to limit cell death in myocardial tissue and thereby reduce infarct size and improve the healing phase to increase postinfarct myocardial performance.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"659-725"},"PeriodicalIF":33.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10033541","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":"Lung endothelium, tau, and amyloids in health and disease.","authors":"Ron Balczon, Mike T Lin, Sarah Voth, Amy R Nelson, Jonas C Schupp, Brant M Wagener, Jean-Francois Pittet, Troy Stevens","doi":"10.1152/physrev.00006.2023","DOIUrl":"10.1152/physrev.00006.2023","url":null,"abstract":"<p><p>Lung endothelia in the arteries, capillaries, and veins are heterogeneous in structure and function. Lung capillaries in particular represent a unique vascular niche, with a thin yet highly restrictive alveolar-capillary barrier that optimizes gas exchange. Capillary endothelium surveys the blood while simultaneously interpreting cues initiated within the alveolus and communicated via immediately adjacent type I and type II epithelial cells, fibroblasts, and pericytes. This cell-cell communication is necessary to coordinate the immune response to lower respiratory tract infection. Recent discoveries identify an important role for the microtubule-associated protein tau that is expressed in lung capillary endothelia in the host-pathogen interaction. This endothelial tau stabilizes microtubules necessary for barrier integrity, yet infection drives production of cytotoxic tau variants that are released into the airways and circulation, where they contribute to end-organ dysfunction. Similarly, beta-amyloid is produced during infection. Beta-amyloid has antimicrobial activity, but during infection it can acquire cytotoxic activity that is deleterious to the host. The production and function of these cytotoxic tau and amyloid variants are the subject of this review. Lung-derived cytotoxic tau and amyloid variants are a recently discovered mechanism of end-organ dysfunction, including neurocognitive dysfunction, during and in the aftermath of infection.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"533-587"},"PeriodicalIF":29.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9957916","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":"Community-acquired bacterial coinfections and COVID-19.","authors":"Michael John Patton,&nbsp;Amit Gaggar,&nbsp;Matthew Might,&nbsp;Nathaniel Erdmann,&nbsp;Carlos J Orihuela,&nbsp;Kevin S Harrod","doi":"10.1152/physrev.00010.2023","DOIUrl":"10.1152/physrev.00010.2023","url":null,"abstract":"","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1-21"},"PeriodicalIF":33.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10016545","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":"Tissue transglutaminase: a multifunctional and multisite regulator in health and disease.","authors":"Zhouzhou Yao, Yuhua Fan, Lizhen Lin, Rodney E Kellems, Yang Xia","doi":"10.1152/physrev.00003.2023","DOIUrl":"10.1152/physrev.00003.2023","url":null,"abstract":"<p><p>Tissue transglutaminase (TG2) is a widely distributed multifunctional protein involved in a broad range of cellular and metabolic functions carried out in a variety of cellular compartments. In addition to transamidation, TG2 also functions as a Gα signaling protein, a protein disulfide isomerase (PDI), a protein kinase, and a scaffolding protein. In the nucleus, TG2 modifies histones and transcription factors. The PDI function catalyzes the trimerization and activation of heat shock factor-1 in the nucleus and regulates the oxidation state of several mitochondrial complexes. Cytosolic TG2 modifies proteins by the addition of serotonin or other primary amines and in this way affects cell signaling. Modification of protein-bound glutamines reduces ubiquitin-dependent proteasomal degradation. At the cell membrane, TG2 is associated with G protein-coupled receptors (GPCRs), where it functions in transmembrane signaling. TG2 is also found in the extracellular space, where it functions in protein cross-linking and extracellular matrix stabilization. Of particular importance in transglutaminase research are recent findings concerning the role of TG2 in gene expression, protein homeostasis, cell signaling, autoimmunity, inflammation, and hypoxia. Thus, TG2 performs a multitude of functions in multiple cellular compartments, making it one of the most versatile cellular proteins. Additional evidence links TG2 with multiple human diseases including preeclampsia, hypertension, cardiovascular disease, organ fibrosis, cancer, neurodegenerative diseases, and celiac disease. In conclusion, TG2 provides a multifunctional and multisite response to physiological stress.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"281-325"},"PeriodicalIF":33.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10247153","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":"Glucocorticoids, their uses, sexual dimorphisms, and diseases: new concepts, mechanisms, and discoveries.","authors":"Genesee J Martinez, Malik Appleton, Zachary A Kipp, Analia S Loria, Booki Min, Terry D Hinds","doi":"10.1152/physrev.00021.2023","DOIUrl":"10.1152/physrev.00021.2023","url":null,"abstract":"<p><p>The normal stress response in humans is governed by the hypothalamic-pituitary-adrenal (HPA) axis through heightened mechanisms during stress, raising blood levels of the glucocorticoid hormone cortisol. Glucocorticoids are quintessential compounds that balance the proper functioning of numerous systems in the mammalian body. They are also generated synthetically and are the preeminent therapy for inflammatory diseases. They act by binding to the nuclear receptor transcription factor glucocorticoid receptor (GR), which has two main isoforms (GRα and GRβ). Our classical understanding of glucocorticoid signaling is from the GRα isoform, which binds the hormone, whereas GRβ has no known ligands. With glucocorticoids being involved in many physiological and cellular processes, even small disruptions in their release via the HPA axis, or changes in GR isoform expression, can have dire ramifications on health. Long-term chronic glucocorticoid therapy can lead to a glucocorticoid-resistant state, and we deliberate how this impacts disease treatment. Chronic glucocorticoid treatment can lead to noticeable side effects such as weight gain, adiposity, diabetes, and others that we discuss in detail. There are sexually dimorphic responses to glucocorticoids, and women tend to have a more hyperresponsive HPA axis than men. This review summarizes our understanding of glucocorticoids and critically analyzes the GR isoforms and their beneficial and deleterious mechanisms and the sexual differences that cause a dichotomy in responses. We also discuss the future of glucocorticoid therapy and propose a new concept of dual GR isoform agonist and postulate why activating both isoforms may prevent glucocorticoid resistance.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"473-532"},"PeriodicalIF":29.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41125524","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":"Sex differences in blood pressure regulation and hypertension: renal, hemodynamic, and hormonal mechanisms.","authors":"Erika R Drury, Jing Wu, Joseph C Gigliotti, Thu H Le","doi":"10.1152/physrev.00041.2022","DOIUrl":"10.1152/physrev.00041.2022","url":null,"abstract":"<p><p>The teleology of sex differences has been argued since at least as early as Aristotle's controversial <i>Generation of Animals</i> more than 300 years BC, which reflects the sex bias of the time to contemporary readers. Although the question \"why are the sexes different\" remains a topic of debate in the present day in metaphysics, the recent emphasis on sex comparison in research studies has led to the question \"how are the sexes different\" being addressed in health science through numerous observational studies in both health and disease susceptibility, including blood pressure regulation and hypertension. These efforts have resulted in better understanding of differences in males and females at the molecular level that partially explain their differences in vascular function and renal sodium handling and hence blood pressure and the consequential cardiovascular and kidney disease risks in hypertension. This review focuses on clinical studies comparing differences between men and women in blood pressure over the life span and response to dietary sodium and highlights experimental models investigating sexual dimorphism in the renin-angiotensin-aldosterone, vascular, sympathetic nervous, and immune systems, endothelin, the major renal sodium transporters/exchangers/channels, and the impact of sex hormones on these systems in blood pressure homeostasis. Understanding the mechanisms governing sex differences in blood pressure regulation could guide novel therapeutic approaches in a sex-specific manner to lower cardiovascular risks in hypertension and advance personalized medicine.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"199-251"},"PeriodicalIF":29.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9867092","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":"Recent insights into channelopathies.","authors":"Osama F Harraz, Eric Delpire","doi":"10.1152/physrev.00022.2023","DOIUrl":"10.1152/physrev.00022.2023","url":null,"abstract":"","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"23-31"},"PeriodicalIF":33.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10046282","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":"Ca²⁺ dynamics in interstitial cells: foundational mechanisms for the motor patterns in the gastrointestinal tract.","authors":"Kenton M Sanders, Bernard T Drumm, Caroline A Cobine, Salah A Baker","doi":"10.1152/physrev.00036.2022","DOIUrl":"10.1152/physrev.00036.2022","url":null,"abstract":"<p><p>The gastrointestinal (GI) tract displays multiple motor patterns that move nutrients and wastes through the body. Smooth muscle cells (SMCs) provide the forces necessary for GI motility, but interstitial cells, electrically coupled to SMCs, tune SMC excitability, transduce inputs from enteric motor neurons, and generate pacemaker activity that underlies major motor patterns, such as peristalsis and segmentation. The interstitial cells regulating SMCs are interstitial cells of Cajal (ICC) and PDGF receptor (PDGFR)α⁺ cells. Together these cells form the SIP syncytium. ICC and PDGFRα⁺ cells express signature Ca²⁺-dependent conductances: ICC express Ca²⁺-activated Cl^- channels, encoded by <i>Ano1</i>, that generate inward current, and PDGFRα⁺ cells express Ca²⁺-activated K⁺ channels, encoded by <i>Kcnn3</i>, that generate outward current. The open probabilities of interstitial cell conductances are controlled by Ca²⁺ release from the endoplasmic reticulum. The resulting Ca²⁺ transients occur spontaneously in a stochastic manner. Ca²⁺ transients in ICC induce spontaneous transient inward currents and spontaneous transient depolarizations (STDs). Neurotransmission increases or decreases Ca²⁺ transients, and the resulting depolarizing or hyperpolarizing responses conduct to other cells in the SIP syncytium. In pacemaker ICC, STDs activate voltage-dependent Ca²⁺ influx, which initiates a cluster of Ca²⁺ transients and sustains activation of ANO1 channels and depolarization during slow waves. Regulation of GI motility has traditionally been described as neurogenic and myogenic. Recent advances in understanding Ca²⁺ handling mechanisms in interstitial cells and how these mechanisms influence motor patterns of the GI tract suggest that the term \"myogenic\" should be replaced by the term \"SIPgenic,\" as this review discusses.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"329-398"},"PeriodicalIF":29.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10005435","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":"Sympathetic circuits regulating hepatic glucose metabolism: where we stand.","authors":"Andrea Zsombok, Lucie D Desmoulins, Andrei V Derbenev","doi":"10.1152/physrev.00005.2023","DOIUrl":"10.1152/physrev.00005.2023","url":null,"abstract":"<p><p>The prevalence of metabolic disorders, including type 2 diabetes mellitus, continues to increase worldwide. Although newer and more advanced therapies are available, current treatments are still inadequate and the search for solutions remains. The regulation of energy homeostasis, including glucose metabolism, involves an exchange of information between the nervous systems and peripheral organs and tissues; therefore, developing treatments to alter central and/or peripheral neural pathways could be an alternative solution to modulate whole body metabolism. Liver glucose production and storage are major mechanisms controlling glycemia, and the autonomic nervous system plays an important role in the regulation of hepatic functions. Autonomic nervous system imbalance contributes to excessive hepatic glucose production and thus to the development and progression of type 2 diabetes mellitus. At cellular levels, change in neuronal activity is one of the underlying mechanisms of autonomic imbalance; therefore, modulation of the excitability of neurons involved in autonomic outflow governance has the potential to improve glycemic status. Tissue-specific subsets of preautonomic neurons differentially control autonomic outflow; therefore, detailed information about neural circuits and properties of liver-related neurons is necessary for the development of strategies to regulate liver functions via the autonomic nerves. This review provides an overview of our current understanding of the hypothalamus-ventral brainstem-liver pathway involved in the sympathetic regulation of the liver, outlines strategies to identify organ-related neurons, and summarizes neuronal plasticity during diabetic conditions with a particular focus on liver-related neurons in the paraventricular nucleus.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"85-101"},"PeriodicalIF":29.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9764341","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}