Comprehensive Physiology最新文献_第2页

Familial Hyperkalemic Hypertension. 家族性高钾血症高血压。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2024-12-19 DOI: 10.1002/cphy.c240004

Ryan J Cornelius, Yujiro Maeoka, Ujwal Shinde, James A McCormick

{"title":"Familial Hyperkalemic Hypertension.","authors":"Ryan J Cornelius, Yujiro Maeoka, Ujwal Shinde, James A McCormick","doi":"10.1002/cphy.c240004","DOIUrl":"https://doi.org/10.1002/cphy.c240004","url":null,"abstract":"The rare disease Familial Hyperkalemic Hypertension (FHHt) is caused by mutations in the genes encoding Cullin 3 (CUL3), Kelch-Like 3 (KLHL3), and two members of the With-No-Lysine [K] (WNK) kinase family, WNK1 and WNK4. In the kidney, these mutations ultimately cause hyperactivation of NCC along the renal distal convoluted tubule. Hypertension results from increased NaCl retention, and hyperkalemia by impaired K + secretion by downstream nephron segments. CUL3 and KLHL3 are now known to form a ubiquitin ligase complex that promotes proteasomal degradation of WNK kinases, which activate downstream kinases that phosphorylate and thus activate NCC. For CUL3, potent effects on the vasculature that contribute to the more severe hypertensive phenotype have also been identified. Here we outline the in vitro and in vivo studies that led to the discovery of the molecular pathways regulating NCC and vascular tone, and how FHHt-causing mutations disrupt these pathways. Potential mechanisms for variability in disease severity related to differential effects of each mutation on the kidney and vasculature are described, and other possible effects of the mutant proteins beyond the kidney and vasculature are explored. © 2024 American Physiological Society. Compr Physiol 14:5839-5874, 2024.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 5","pages":"5839-5874"},"PeriodicalIF":4.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853292","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

Issue Information. 问题的信息。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2024-12-19 DOI: 10.1002/cphy.cv14i05

引用次数: 0

Prenatal Origins of Obstructive Airway Disease: Starting on the Wrong Trajectory? 阻塞性气道疾病的产前起源：从错误的轨迹开始？

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2024-12-19 DOI: 10.1002/cphy.c230019

Kimberley C W Wang, Alan L James, Graham M Donovan, Peter B Noble

{"title":"Prenatal Origins of Obstructive Airway Disease: Starting on the Wrong Trajectory?","authors":"Kimberley C W Wang, Alan L James, Graham M Donovan, Peter B Noble","doi":"10.1002/cphy.c230019","DOIUrl":"https://doi.org/10.1002/cphy.c230019","url":null,"abstract":"From the results of well-performed population health studies, we now have excellent data demonstrating that deficits in adult lung function may be present early in life, possibly as a result of developmental disorders, incurring a lifelong risk of obstructive airway diseases such as asthma and chronic obstructive pulmonary disease. Suboptimal fetal development results in intrauterine growth restriction and low birth weight at term (an outcome distinct from preterm complications), which are associated with subsequent obstructive disease. Numerous prenatal exposures and disorders compromise fetal development and these are summarized herein. Various physiological, structural, and mechanical abnormalities may result from prenatal disruption, including changes to airway smooth muscle structure-function, goblet cell biology, airway stiffness, geometry of the bronchial tree, lung parenchymal structure and mechanics, respiratory skeletal muscle contraction, and pulmonary inflammation. The literature therefore supports the need for early life intervention to prevent or correct growth defects, which may include simple nutritional or antioxidant therapy. © 2024 American Physiological Society. Compr Physiol 14:5729-5762, 2024.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 5","pages":"5729-5762"},"PeriodicalIF":4.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853349","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

Mitochondrial Function and Dysfunction in White Adipocytes and Therapeutic Implications. 白色脂肪细胞的线粒体功能和功能障碍及其治疗意义

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2024-10-09 DOI: 10.1002/cphy.c230009

Fenfen Wang, Phu M Huynh, Yu A An

{"title":"Mitochondrial Function and Dysfunction in White Adipocytes and Therapeutic Implications.","authors":"Fenfen Wang, Phu M Huynh, Yu A An","doi":"10.1002/cphy.c230009","DOIUrl":"https://doi.org/10.1002/cphy.c230009","url":null,"abstract":"For a long time, white adipocytes were thought to function as lipid storages due to the sizeable unilocular lipid droplet that occupies most of their space. However, recent discoveries have highlighted the critical role of white adipocytes in maintaining energy homeostasis and contributing to obesity and related metabolic diseases. These physiological and pathological functions depend heavily on the mitochondria that reside in white adipocytes. This article aims to provide an up-to-date overview of the recent research on the function and dysfunction of white adipocyte mitochondria. After briefly summarizing the fundamental aspects of mitochondrial biology, the article describes the protective role of functional mitochondria in white adipocyte and white adipose tissue health and various roles of dysfunctional mitochondria in unhealthy white adipocytes and obesity. Finally, the article emphasizes the importance of enhancing mitochondrial quantity and quality as a therapeutic avenue to correct mitochondrial dysfunction, promote white adipocyte browning, and ultimately improve obesity and its associated metabolic diseases. © 2024 American Physiological Society. Compr Physiol 14:5581-5640, 2024.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 4","pages":"5581-5640"},"PeriodicalIF":4.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388696","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

Maternal Microvascular Dysfunction During and After Preeclamptic Pregnancy. 先兆子痫妊娠期间和之后的母体微血管功能障碍

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2024-10-09 DOI: 10.1002/cphy.c240003

Kelsey S Schwartz, Anna E Stanhewicz

{"title":"Maternal Microvascular Dysfunction During and After Preeclamptic Pregnancy.","authors":"Kelsey S Schwartz, Anna E Stanhewicz","doi":"10.1002/cphy.c240003","DOIUrl":"10.1002/cphy.c240003","url":null,"abstract":"Preeclampsia, a pregnancy disorder characterized by de novo hypertension and maternal multisystem organ dysfunction, is the leading cause of maternal mortality worldwide and is associated with a fourfold greater risk of cardiovascular disease throughout the lifespan. Current understanding of the etiology of preeclampsia remains unclear, due in part to the varying phenotypical presentations of the disease, which has hindered the development of effective and mechanism-specific treatment or prevention strategies both during and after the affected pregnancy. These maternal sequelae of preeclampsia are symptoms of systemic vascular dysfunction in the maternal nonreproductive microvascular beds that drives the development and progression of adverse cardiovascular outcomes during preeclampsia. Despite normalization of vascular disturbances after delivery, subclinical dysfunction persists in the nonreproductive microvascular beds, contributing to an increased lifetime risk of cardiovascular and metabolic diseases and all-cause mortality. Given that women with a history of preeclampsia demonstrate vascular dysfunction despite an absence of traditional CVD risk factors, an understanding of the underlying mechanisms of microvascular dysfunction during and after preeclampsia is essential to identify potential therapeutic avenues to mitigate or reverse the development of overt disease. This article aims to provide a summary of the existing literature on the pathophysiology of maternal microvascular dysfunction during preeclampsia, the mechanisms underlying the residual dysfunction that remains after delivery, and current and potential treatments both during and after the affected pregnancy that may reduce microvascular dysfunction in these high-risk women. © 2024 American Physiological Society. Compr Physiol 14:5703-5727, 2024.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 4","pages":"5703-5727"},"PeriodicalIF":4.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388695","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

Neuromuscular Transmission in a Biological Context. 生物学背景下的神经肌肉传递。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2024-10-09 DOI: 10.1002/cphy.c240001

Clarke R Slater

{"title":"Neuromuscular Transmission in a Biological Context.","authors":"Clarke R Slater","doi":"10.1002/cphy.c240001","DOIUrl":"https://doi.org/10.1002/cphy.c240001","url":null,"abstract":"Neuromuscular transmission is the process by which motor neurons activate muscle contraction and thus plays an essential role in generating the purposeful body movements that aid survival. While many features of this process are common throughout the Animal Kingdom, such as the release of transmitter in multimolecular \"quanta,\" and the response to it by opening ligand-gated postsynaptic ion channels, there is also much diversity between and within species. Much of this diversity is associated with specialization for either slow, sustained movements such as maintain posture or fast but brief movements used during escape or prey capture. In invertebrates, with hydrostatic and exoskeletons, most motor neurons evoke graded depolarizations of the muscle which cause graded muscle contractions. By contrast, vertebrate motor neurons trigger action potentials in the muscle fibers which give rise to all-or-none contractions. The properties of neuromuscular transmission, in particular the intensity and persistence of transmitter release, reflect these differences. Neuromuscular transmission varies both between and within individual animals, which often have distinct tonic and phasic subsystems. Adaptive plasticity of neuromuscular transmission, on a range of time scales, occurs in many species. This article describes the main steps in neuromuscular transmission and how they vary in a number of \"model\" species, including C. elegans , Drosophila , zebrafish, mice, and humans. © 2024 American Physiological Society. Compr Physiol 14:5641-5702, 2024.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 4","pages":"5641-5702"},"PeriodicalIF":4.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388697","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

Function and Regulation of Bone Marrow Adipose Tissue in Health and Disease: State of the Field and Clinical Considerations. 健康与疾病中骨髓脂肪组织的功能和调节：领域现状与临床考虑。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2024-06-27 DOI: 10.1002/cphy.c230016

Xiao Zhang, Linda Tian, Anurag Majumdar, Erica L Scheller

{"title":"Function and Regulation of Bone Marrow Adipose Tissue in Health and Disease: State of the Field and Clinical Considerations.","authors":"Xiao Zhang, Linda Tian, Anurag Majumdar, Erica L Scheller","doi":"10.1002/cphy.c230016","DOIUrl":"10.1002/cphy.c230016","url":null,"abstract":"Bone marrow adipose tissue (BMAT) is a metabolically and clinically relevant fat depot that exists within bone. Two subtypes of BMAT, regulated and constitutive, reside in hematopoietic-rich red marrow and fatty yellow marrow, respectively, and exhibit distinct characteristics compared to peripheral fat such as white and brown adipose tissues. Bone marrow adipocytes (BMAds) are evolutionally preserved in most vertebrates, start development after birth and expand throughout life, and originate from unique progenitor populations that control bone formation and hematopoiesis. Mature BMAds also interact closely with other cellular components of the bone marrow niche, serving as a nearby energy reservoir to support the skeletal system, a signaling hub that contributes to both local and systemic homeostasis, and a final fuel reserve for survival during starvation. Though BMAT and bone are often inversely correlated, more BMAT does not always mean less bone, and the prevention of BMAT expansion as a strategy to prevent bone loss remains questionable. BMAT adipogenesis and lipid metabolism are regulated by the nervous systems and a variety of circulating hormones. This contributes to the plasticity of BMAT, including BMAT expansion in common physiological or pathological conditions, and BMAT catabolism under certain extreme circumstances, which are often associated with malnutrition and/or systemic inflammation. Altogether, this article provides a comprehensive overview of the local and systemic functions of BMAT and discusses the regulation and plasticity of this unique adipose tissue depot in health and disease. © 2024 American Physiological Society. Compr Physiol 14:5521-5579, 2024.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 3","pages":"5521-5579"},"PeriodicalIF":4.2,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897001","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

Human Gut Microbiota in Cardiovascular Disease. 心血管疾病中的人体肠道微生物群。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2024-06-27 DOI: 10.1002/cphy.c230012

Daniel Ronen, Yair Rokach, Suzan Abedat, Abed Qadan, Samar Daana, Offer Amir, Rabea Asleh

{"title":"Human Gut Microbiota in Cardiovascular Disease.","authors":"Daniel Ronen, Yair Rokach, Suzan Abedat, Abed Qadan, Samar Daana, Offer Amir, Rabea Asleh","doi":"10.1002/cphy.c230012","DOIUrl":"https://doi.org/10.1002/cphy.c230012","url":null,"abstract":"The gut ecosystem, termed microbiota, is composed of bacteria, archaea, viruses, protozoa, and fungi and is estimated to outnumber human cells. Microbiota can affect the host by multiple mechanisms, including the synthesis of metabolites and toxins, modulating inflammation and interaction with other organisms. Advances in understanding commensal organisms' effect on human conditions have also elucidated the importance of this community for cardiovascular disease (CVD). This effect is driven by both direct CV effects and conditions known to increase CV risk, such as obesity, diabetes mellitus (DM), hypertension, and renal and liver diseases. Cardioactive metabolites, such as trimethylamine N -oxide (TMAO), short-chain fatty acids (SCFA), lipopolysaccharides, bile acids, and uremic toxins, can affect atherosclerosis, platelet activation, and inflammation, resulting in increased CV incidence. Interestingly, this interaction is bidirectional with microbiota affected by multiple host conditions including diet, bile acid secretion, and multiple diseases affecting the gut barrier. This interdependence makes manipulating microbiota an attractive option to reduce CV risk. Indeed, evolving data suggest that the benefits observed from low red meat and Mediterranean diet consumption can be explained, at least partially, by the changes that these diets may have on the gut microbiota. In this article, we depict the current epidemiological and mechanistic understanding of the role of microbiota and CVD. Finally, we discuss the potential therapeutic approaches aimed at manipulating gut microbiota to improve CV outcomes. © 2024 American Physiological Society. Compr Physiol 14:5449-5490, 2024.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 3","pages":"5449-5490"},"PeriodicalIF":4.2,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897002","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 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":"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