Comprehensive Physiology最新文献_第2页

The Human Microbiome-A Physiologic Perspective. 人类微生物组--生理学的视角。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2024-06-27 DOI: 10.1002/cphy.c230013

Yang Xiao, Tijs Louwies, Ruben A T Mars, Purna C Kashyap

{"title":"The Human Microbiome-A Physiologic Perspective.","authors":"Yang Xiao, Tijs Louwies, Ruben A T Mars, Purna C Kashyap","doi":"10.1002/cphy.c230013","DOIUrl":"https://doi.org/10.1002/cphy.c230013","url":null,"abstract":"The human microbiome consists of the microorganisms associated with the body, such as bacteria, fungi, archaea, protozoa, and viruses, along with their gene content and products. These microbes are abundant in the digestive, respiratory, renal/urinary, and reproductive systems. While microbes found in other organs/tissues are often associated with diseases, some reports suggest their presence even in healthy individuals. Lack of microbial colonization does not indicate a lack of microbial influence, as their metabolites can affect distant locations through circulation. In a healthy state, these microbes maintain a mutualistic relationship and help shape the host's physiological functions. Unlike the host's genetic content, microbial gene content and expression are dynamic and influenced by factors such as ethnicity, genetic background, sex, age, lifestyle/diet, and psychological/physical conditions. Therefore, defining a healthy microbiome becomes challenging as it is context dependent and can vary over time for an individual. Although differences in microbial composition have been observed in various diseases, these changes may reflect host alterations rather than causing the disease itself. As the field is evolving, there is increased emphasis on understanding when changes in the microbiome are an important component of pathogenesis rather than the consequence of a disease state. This article focuses on the microbial component in the digestive and respiratory tracts-the primary sites colonized by microorganisms-and the physiological functions of microbial metabolites in these systems. It also discusses their physiological functions in the central nervous and cardiovascular systems, which have no microorganism colonization under healthy conditions based on human studies. © 2024 American Physiological Society. Compr Physiol 14:5491-5519, 2024.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 3","pages":"5491-5519"},"PeriodicalIF":4.2,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897003","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 TRP to Pathological Angiogenesis and Vascular Normalization. 病态血管生成和血管正常化的 TRP。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2024-03-29 DOI: 10.1002/cphy.c230014

Venkatesh Katari, Kesha Dalal, Ravi K Adapala, Brianna D Guarino, Narendrababu Kondapalli, Sailaja Paruchuri, Charles K Thodeti

{"title":"A TRP to Pathological Angiogenesis and Vascular Normalization.","authors":"Venkatesh Katari, Kesha Dalal, Ravi K Adapala, Brianna D Guarino, Narendrababu Kondapalli, Sailaja Paruchuri, Charles K Thodeti","doi":"10.1002/cphy.c230014","DOIUrl":"https://doi.org/10.1002/cphy.c230014","url":null,"abstract":"Uncontrolled angiogenesis underlies various pathological conditions such as cancer, age-related macular degeneration (AMD), and proliferative diabetic retinopathy (PDR). Hence, targeting pathological angiogenesis has become a promising strategy for the treatment of cancer and neovascular ocular diseases. However, current pharmacological treatments that target VEGF signaling have met with limited success either due to acquiring resistance against anti-VEGF therapies with serious side effects including nephrotoxicity and cardiovascular-related adverse effects in cancer patients or retinal vasculitis and intraocular inflammation after intravitreal injection in patients with AMD or PDR. Therefore, there is an urgent need to develop novel strategies which can control multiple aspects of the pathological microenvironment and regulate the process of abnormal angiogenesis. To this end, vascular normalization has been proposed as an alternative for antiangiogenesis approach; however, these strategies still focus on targeting VEGF or FGF or PDGF which has shown adverse effects. In addition to these growth factors, calcium has been recently implicated as an important modulator of tumor angiogenesis. This article provides an overview on the role of major calcium channels in endothelium, TRP channels, with a special focus on TRPV4 and its downstream signaling pathways in the regulation of pathological angiogenesis and vascular normalization. We also highlight recent findings on the modulation of TRPV4 activity and endothelial phenotypic transformation by tumor microenvironment through Rho/YAP/VEGFR2 mechanotranscriptional pathways. Finally, we provide perspective on endothelial TRPV4 as a novel VEGF alternative therapeutic target for vascular normalization and improved therapy. © 2024 American Physiological Society. Compr Physiol 14:5389-5406, 2024.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 2","pages":"5389-5406"},"PeriodicalIF":4.2,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896998","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

Epithelial Na ⁺ Channels Function as Extracellular Sensors. 上皮细胞 Na + 通道作为细胞外传感器发挥作用

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2024-03-29 DOI: 10.1002/cphy.c230015

Ossama B Kashlan, Xue-Ping Wang, Shaohu Sheng, Thomas R Kleyman

{"title":"Epithelial Na + Channels Function as Extracellular Sensors.","authors":"Ossama B Kashlan, Xue-Ping Wang, Shaohu Sheng, Thomas R Kleyman","doi":"10.1002/cphy.c230015","DOIUrl":"10.1002/cphy.c230015","url":null,"abstract":"The epithelial Na + channel (ENaC) resides on the apical surfaces of specific epithelia in vertebrates and plays a critical role in extracellular fluid homeostasis. Evidence that ENaC senses the external environment emerged well before the molecular identity of the channel was reported three decades ago. This article discusses progress toward elucidating the mechanisms through which specific external factors regulate ENaC function, highlighting insights gained from structural studies of ENaC and related family members. It also reviews our understanding of the role of ENaC regulation by the extracellular environment in physiology and disease. After familiarizing the reader with the channel's physiological roles and structure, we describe the central role protein allostery plays in ENaC's sensitivity to the external environment. We then discuss each of the extracellular factors that directly regulate the channel: proteases, cations and anions, shear stress, and other regulators specific to particular extracellular compartments. For each regulator, we discuss the initial observations that led to discovery, studies investigating molecular mechanism, and the physiological and pathophysiological implications of regulation. © 2024 American Physiological Society. Compr Physiol 14:5407-5447, 2024.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 2","pages":"1-41"},"PeriodicalIF":4.2,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11309579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896999","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

Pancreatic Crosstalk in the Disease Setting: Understanding the Impact of Exocrine Disease on Endocrine Function. 疾病背景下的胰腺串联：了解外分泌疾病对内分泌功能的影响。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2024-03-29 DOI: 10.1002/cphy.c230008

Catharina B P Villaca, Teresa L Mastracci

{"title":"Pancreatic Crosstalk in the Disease Setting: Understanding the Impact of Exocrine Disease on Endocrine Function.","authors":"Catharina B P Villaca, Teresa L Mastracci","doi":"10.1002/cphy.c230008","DOIUrl":"10.1002/cphy.c230008","url":null,"abstract":"The exocrine and endocrine are functionally distinct compartments of the pancreas that have traditionally been studied as separate entities. However, studies of embryonic development, adult physiology, and disease pathogenesis suggest there may be critical communication between exocrine and endocrine cells. In fact, the incidence of the endocrine disease diabetes secondary to exocrine disease/dysfunction ranges from 25% to 80%, depending on the type and severity of the exocrine pathology. Therefore, it is necessary to investigate how exocrine-endocrine \"crosstalk\" may impact pancreatic function. In this article, we discuss common exocrine diseases, including cystic fibrosis, acute, hereditary, and chronic pancreatitis, and the impact of these exocrine diseases on endocrine function. Additionally, we review how obesity and fatty pancreas influence exocrine function and the impact on cellular communication between the exocrine and endocrine compartments. Interestingly, in all pathologies, there is evidence that signals from the exocrine disease contribute to endocrine dysfunction and the progression to diabetes. Continued research efforts to identify the mechanisms that underlie the crosstalk between various cell types in the pancreas are critical to understanding normal pancreatic physiology as well as disease states. © 2024 American Physiological Society. Compr Physiol 14:5371-5387, 2024.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 2","pages":"5371-5387"},"PeriodicalIF":4.2,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897000","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

Advanced Imaging Techniques for the Characterization of Subcellular Organelle Structure in Pancreatic Islet β Cells. 用于表征胰岛β细胞亚细胞器结构的先进成像技术。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2023-12-29 DOI: 10.1002/cphy.c230002

Madeline R McLaughlin, Staci A Weaver, Farooq Syed, Carmella Evans-Molina

{"title":"Advanced Imaging Techniques for the Characterization of Subcellular Organelle Structure in Pancreatic Islet β Cells.","authors":"Madeline R McLaughlin, Staci A Weaver, Farooq Syed, Carmella Evans-Molina","doi":"10.1002/cphy.c230002","DOIUrl":"10.1002/cphy.c230002","url":null,"abstract":"Type 2 diabetes (T2D) affects more than 32.3 million individuals in the United States, creating an economic burden of nearly $966 billion in 2021. T2D results from a combination of insulin resistance and inadequate insulin secretion from the pancreatic β cell. However, genetic and physiologic data indicate that defects in β cell function are the chief determinant of whether an individual with insulin resistance will progress to a diagnosis of T2D. The subcellular organelles of the insulin secretory pathway, including the endoplasmic reticulum, Golgi apparatus, and secretory granules, play a critical role in maintaining the heavy biosynthetic burden of insulin production, processing, and secretion. In addition, the mitochondria enable the process of insulin release by integrating the metabolism of nutrients into energy output. Advanced imaging techniques are needed to determine how changes in the structure and composition of these organelles contribute to the loss of insulin secretory capacity in the β cell during T2D. Several microscopy techniques, including electron microscopy, fluorescence microscopy, and soft X-ray tomography, have been utilized to investigate the structure-function relationship within the β cell. In this overview article, we will detail the methodology, strengths, and weaknesses of each approach. © 2024 American Physiological Society. Compr Physiol 14:5243-5267, 2024.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 1","pages":"5243-5267"},"PeriodicalIF":4.2,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073560","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

Mechanosensing in Metabolism. 新陈代谢中的机械传感

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2023-12-29 DOI: 10.1002/cphy.c230005

John D Tranter, Ashutosh Kumar, Vinayak K Nair, Rajan Sah

{"title":"Mechanosensing in Metabolism.","authors":"John D Tranter, Ashutosh Kumar, Vinayak K Nair, Rajan Sah","doi":"10.1002/cphy.c230005","DOIUrl":"10.1002/cphy.c230005","url":null,"abstract":"Electrical mechanosensing is a process mediated by specialized ion channels, gated directly or indirectly by mechanical forces, which allows cells to detect and subsequently respond to mechanical stimuli. The activation of mechanosensitive (MS) ion channels, intrinsically gated by mechanical forces, or mechanoresponsive (MR) ion channels, indirectly gated by mechanical forces, results in electrical signaling across lipid bilayers, such as the plasma membrane. While the functions of mechanically gated channels within a sensory context (e.g., proprioception and touch) are well described, there is emerging data demonstrating functions beyond touch and proprioception, including mechanoregulation of intracellular signaling and cellular/systemic metabolism. Both MR and MS ion channel signaling have been shown to contribute to the regulation of metabolic dysfunction, including obesity, insulin resistance, impaired insulin secretion, and inflammation. This review summarizes our current understanding of the contributions of several MS/MR ion channels in cell types implicated in metabolic dysfunction, namely, adipocytes, pancreatic β-cells, hepatocytes, and skeletal muscle cells, and discusses MS/MR ion channels as possible therapeutic targets. © 2024 American Physiological Society. Compr Physiol 14:5269-5290, 2024.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 1","pages":"5269-5290"},"PeriodicalIF":4.2,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073564","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

Behavioral Motor Performance. 行为运动表现。

IF 5.8 2区医学

Comprehensive Physiology Pub Date : 2023-12-29 DOI: 10.1002/cphy.c220032

Raz Leib, Ian S Howard, Matthew Millard, David W Franklin

{"title":"Behavioral Motor Performance.","authors":"Raz Leib, Ian S Howard, Matthew Millard, David W Franklin","doi":"10.1002/cphy.c220032","DOIUrl":"10.1002/cphy.c220032","url":null,"abstract":"The human sensorimotor control system has exceptional abilities to perform skillful actions. We easily switch between strenuous tasks that involve brute force, such as lifting a heavy sewing machine, and delicate movements such as threading a needle in the same machine. Using a structure with different control architectures, the motor system is capable of updating its ability to perform through our daily interaction with the fluctuating environment. However, there are issues that make this a difficult computational problem for the brain to solve. The brain needs to control a nonlinear, nonstationary neuromuscular system, with redundant and occasionally undesired degrees of freedom, in an uncertain environment using a body in which information transmission is subject to delays and noise. To gain insight into the mechanisms of motor control, here we survey movement laws and invariances that shape our everyday motion. We then examine the major solutions to each of these problems in the three parts of the sensorimotor control system, sensing, planning, and acting. We focus on how the sensory system, the control architectures, and the structure and operation of the muscles serve as complementary mechanisms to overcome deviations and disturbances to motor behavior and give rise to skillful motor performance. We conclude with possible future research directions based on suggested links between the operation of the sensorimotor system across the movement stages. © 2024 American Physiological Society. Compr Physiol 14:5179-5224, 2024.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 1","pages":"5179-5224"},"PeriodicalIF":5.8,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073561","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

Pathophysiology of Red Blood Cell Trapping in Ischemic Acute Kidney Injury. 缺血性急性肾损伤中红细胞潴留的病理生理学。

IF 5.8 2区医学

Comprehensive Physiology Pub Date : 2023-12-29 DOI: 10.1002/cphy.c230010

Sarah R McLarnon

{"title":"Pathophysiology of Red Blood Cell Trapping in Ischemic Acute Kidney Injury.","authors":"Sarah R McLarnon","doi":"10.1002/cphy.c230010","DOIUrl":"10.1002/cphy.c230010","url":null,"abstract":"Red blood cell (RBC) trapping describes the accumulation of RBCs in the microvasculature of the kidney outer medulla that occurs following ischemic acute kidney injury (AKI). Despite its prominence in human kidneys following AKI, as well as evidence from experimental models demonstrating that the severity of RBC trapping is directly correlated with renal recovery, to date, RBC trapping has not been a primary focus in understanding the pathogenesis of ischemic kidney injury. New evidence from rodent models suggests that RBC trapping is responsible for much of the tubular injury occurring in the initial hours after kidney reperfusion from ischemia. This early injury appears to result from RBC cytotoxicity and closely reflects the injury profile observed in human kidneys, including sloughing of the medullary tubules and the formation of heme casts in the distal tubules. In this review, we discuss what is currently known about RBC trapping. We conclude that RBC trapping is likely avoidable. The primary causes of RBC trapping are thought to include rheologic alterations, blood coagulation, tubular cell swelling, and increased vascular permeability; however, new data indicate that a mismatch in blood flow between the cortex and medulla where medullary perfusion is maintained during cortical ischemia is also likely critical. The mechanism(s) by which RBC trapping contributes to renal functional decline require more investigation. We propose a renewed focus on the mechanisms mediating RBC trapping, and RBC trapping-associated injury is likely to provide important knowledge for improving AKI outcomes. © 2024 American Physiological Society. Compr Physiol 14:5325-5343, 2024.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 1","pages":"5325-5343"},"PeriodicalIF":5.8,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073565","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

Environmental Enrichment for Stroke and Traumatic Brain Injury: Mechanisms and Translational Implications. 中风和创伤性脑损伤的环境富集：机制与转化影响》。

IF 5.8 2区医学

Comprehensive Physiology Pub Date : 2023-12-29 DOI: 10.1002/cphy.c230007

Luwei Nie, Jinxin He, Junmin Wang, Ruike Wang, Leo Huang, Lin Jia, Yun Tai Kim, Ujjal K Bhawal, Xiaochong Fan, Marietta Zille, Chao Jiang, Xuemei Chen, Jian Wang

{"title":"Environmental Enrichment for Stroke and Traumatic Brain Injury: Mechanisms and Translational Implications.","authors":"Luwei Nie, Jinxin He, Junmin Wang, Ruike Wang, Leo Huang, Lin Jia, Yun Tai Kim, Ujjal K Bhawal, Xiaochong Fan, Marietta Zille, Chao Jiang, Xuemei Chen, Jian Wang","doi":"10.1002/cphy.c230007","DOIUrl":"10.1002/cphy.c230007","url":null,"abstract":"Acquired brain injuries, such as ischemic stroke, intracerebral hemorrhage (ICH), and traumatic brain injury (TBI), can cause severe neurologic damage and even death. Unfortunately, currently, there are no effective and safe treatments to reduce the high disability and mortality rates associated with these brain injuries. However, environmental enrichment (EE) is an emerging approach to treating and rehabilitating acquired brain injuries by promoting motor, sensory, and social stimulation. Multiple preclinical studies have shown that EE benefits functional recovery, including improved motor and cognitive function and psychological benefits mediated by complex protective signaling pathways. This article provides an overview of the enriched environment protocols used in animal models of ischemic stroke, ICH, and TBI, as well as relevant clinical studies, with a particular focus on ischemic stroke. Additionally, we explored studies of animals with stroke and TBI exposed to EE alone or in combination with multiple drugs and other rehabilitation modalities. Finally, we discuss the potential clinical applications of EE in future brain rehabilitation therapy and the molecular and cellular changes caused by EE in rodents with stroke or TBI. This article aims to advance preclinical and clinical research on EE rehabilitation therapy for acquired brain injury. © 2024 American Physiological Society. Compr Physiol 14:5291-5323, 2024.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 1","pages":"5291-5323"},"PeriodicalIF":5.8,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073562","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

Integrated Functions of Cardiac Energetics, Mechanics, and Purine Nucleotide Metabolism. 心脏能量学、力学和嘌呤核苷酸代谢的综合功能。

IF 5.8 2区医学

Comprehensive Physiology Pub Date : 2023-12-29 DOI: 10.1002/cphy.c230011

Rachel Lopez-Schenk, Nicole L Collins, Noah A Schenk, Daniel A Beard

{"title":"Integrated Functions of Cardiac Energetics, Mechanics, and Purine Nucleotide Metabolism.","authors":"Rachel Lopez-Schenk, Nicole L Collins, Noah A Schenk, Daniel A Beard","doi":"10.1002/cphy.c230011","DOIUrl":"10.1002/cphy.c230011","url":null,"abstract":"Purine nucleotides play central roles in energy metabolism in the heart. Most fundamentally, the free energy of hydrolysis of the adenine nucleotide adenosine triphosphate (ATP) provides the thermodynamic driving force for numerous cellular processes including the actin-myosin crossbridge cycle. Perturbations to ATP supply and/or demand in the myocardium lead to changes in the homeostatic balance between purine nucleotide synthesis, degradation, and salvage, potentially affecting myocardial energetics and, consequently, myocardial mechanics. Indeed, both acute myocardial ischemia and decompensatory remodeling of the myocardium in heart failure are associated with depletion of myocardial adenine nucleotides and with impaired myocardial mechanical function. Yet there remain gaps in the understanding of mechanistic links between adenine nucleotide degradation and contractile dysfunction in heart disease. The scope of this article is to: (i) review current knowledge of the pathways of purine nucleotide depletion and salvage in acute ischemia and in chronic heart disease; (ii) review hypothesized mechanisms linking myocardial mechanics and energetics with myocardial adenine nucleotide regulation; and (iii) highlight potential targets for treating myocardial metabolic and mechanical dysfunction associated with these pathways. It is hypothesized that an imbalance in the degradation, salvage, and synthesis of adenine nucleotides leads to a net loss of adenine nucleotides in both acute ischemia and under chronic high-demand conditions associated with the development of heart failure. This reduction in adenine nucleotide levels results in reduced myocardial ATP and increased myocardial inorganic phosphate. Both of these changes have the potential to directly impact tension development and mechanical work at the cellular level. © 2024 American Physiological Society. Compr Physiol 14:5345-5369, 2024.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 1","pages":"5345-5369"},"PeriodicalIF":5.8,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10956446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073563","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