Annual review of physiologyPub Date : 2024-02-12Epub Date: 2023-06-11DOI: 10.1146/annurev-physiol-042222-021346
Murray D Polkinghorne, Henry W West, Charalambos Antoniades
{"title":"Adipose Tissue in Cardiovascular Disease: From Basic Science to Clinical Translation.","authors":"Murray D Polkinghorne, Henry W West, Charalambos Antoniades","doi":"10.1146/annurev-physiol-042222-021346","DOIUrl":"10.1146/annurev-physiol-042222-021346","url":null,"abstract":"<p><p>The perception of adipose tissue as a metabolically quiescent tissue, primarily responsible for lipid storage and energy balance (with some endocrine, thermogenic, and insulation functions), has changed. It is now accepted that adipose tissue is a crucial regulator of metabolic health, maintaining bidirectional communication with other organs including the cardiovascular system. Additionally, adipose tissue depots are functionally and morphologically heterogeneous, acting not only as sources of bioactive molecules that regulate the physiological functioning of the vasculature and myocardium but also as biosensors of the paracrine and endocrine signals arising from these tissues. In this way, adipose tissue undergoes phenotypic switching in response to vascular and/or myocardial signals (proinflammatory, profibrotic, prolipolytic), a process that novel imaging technologies are able to visualize and quantify with implications for clinical prognosis. Furthermore, a range of therapeutic modalities have emerged targeting adipose tissue metabolism and altering its secretome, potentially benefiting those at risk of cardiovascular disease.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":" ","pages":"175-198"},"PeriodicalIF":15.7,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477418","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}
Annual review of physiologyPub Date : 2024-02-12Epub Date: 2023-10-03DOI: 10.1146/annurev-physiol-042022-015223
Jaime Ibarrola, Iris Z Jaffe
{"title":"The Mineralocorticoid Receptor in the Vasculature: Friend or Foe?","authors":"Jaime Ibarrola, Iris Z Jaffe","doi":"10.1146/annurev-physiol-042022-015223","DOIUrl":"10.1146/annurev-physiol-042022-015223","url":null,"abstract":"<p><p>Originally described as the renal aldosterone receptor that regulates sodium homeostasis, it is now clear that mineralocorticoid receptors (MRs) are widely expressed, including in vascular endothelial and smooth muscle cells. Ample data demonstrate that endothelial and smooth muscle cell MRs contribute to cardiovascular disease in response to risk factors (aging, obesity, hypertension, atherosclerosis) by inducing vasoconstriction, vascular remodeling, inflammation, and oxidative stress. Extrapolating from its role in disease, evidence supports beneficial roles of vascular MRs in the context of hypotension by promoting inflammation, wound healing, and vasoconstriction to enhance survival from bleeding or sepsis. Advances in understanding how vascular MRs become activated are also reviewed, describing transcriptional, ligand-dependent, and ligand-independent mechanisms. By synthesizing evidence describing how vascular MRs convert cardiovascular risk factors into disease (the vascular MR as a foe), we postulate that the teleological role of the MR is to coordinate responses to hypotension (the MR as a friend).</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":" ","pages":"49-70"},"PeriodicalIF":18.2,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41107955","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}
Annual review of physiologyPub Date : 2024-02-12Epub Date: 2023-10-31DOI: 10.1146/annurev-physiol-030323-042845
Andrea L Meredith
{"title":"BK Channelopathies and <i>KCNMA1</i>-Linked Disease Models.","authors":"Andrea L Meredith","doi":"10.1146/annurev-physiol-030323-042845","DOIUrl":"10.1146/annurev-physiol-030323-042845","url":null,"abstract":"<p><p>Novel <i>KCNMA1</i> variants<i>,</i> encoding the BK K<sup>+</sup> channel, are associated with a debilitating dyskinesia and epilepsy syndrome. Neurodevelopmental delay, cognitive disability, and brain and structural malformations are also diagnosed at lower incidence. More than half of affected individuals present with a rare negative episodic motor disorder, paroxysmal nonkinesigenic dyskinesia (PNKD3). The mechanistic relationship of PNKD3 to epilepsy and the broader spectrum of <i>KCNMA1</i>-associated symptomology is unknown. This review summarizes patient-associated <i>KCNMA1</i> variants within the BK channel structure, functional classifications, genotype-phenotype associations, disease models, and treatment. Patient and transgenic animal data suggest delineation of gain-of-function (GOF) and loss-of-function <i>KCNMA1</i> neurogenetic disease, validating two heterozygous alleles encoding GOF BK channels (D434G and N999S) as causing seizure and PNKD3. This discovery led to a variant-defined therapeutic approach for PNKD3, providing initial insight into the neurological basis. A comprehensive clinical definition of monogenic <i>KCNMA1</i>-linked disease and the neuronal mechanisms currently remain priorities for continued investigation.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":" ","pages":"277-300"},"PeriodicalIF":18.2,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420176","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}
Geniver El Tekle, Natalia Andreeva, Wendy S Garrett
{"title":"The Role of the Microbiome in the Etiopathogenesis of Colon Cancer.","authors":"Geniver El Tekle, Natalia Andreeva, Wendy S Garrett","doi":"10.1146/annurev-physiol-042022-025619","DOIUrl":"10.1146/annurev-physiol-042022-025619","url":null,"abstract":"<p><p>Studies in preclinical models support that the gut microbiota play a critical role in the development and progression of colorectal cancer (CRC). Specific microbial species and their corresponding virulence factors or associated small molecules can contribute to CRC development and progression either via direct effects on the neoplastic transformation of epithelial cells or through interactions with the host immune system. Induction of DNA damage, activation of Wnt/β-catenin and NF-κB proinflammatory pathways, and alteration of the nutrient's availability and the metabolic activity of cancer cells are the main mechanisms by which the microbiota contribute to CRC. Within the tumor microenvironment, the gut microbiota alter the recruitment, activation, and function of various immune cells, such as T cells, macrophages, and dendritic cells. Additionally, the microbiota shape the function and composition of cancer-associated fibroblasts and extracellular matrix components, fashioning an immunosuppressive and pro-tumorigenic niche for CRC. Understanding the complex interplay between gut microbiota and tumorigenesis can provide therapeutic opportunities for the prevention and treatment of CRC.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":"86 ","pages":"453-478"},"PeriodicalIF":18.2,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721404","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}
Annual review of physiologyPub Date : 2024-02-12Epub Date: 2023-11-27DOI: 10.1146/annurev-physiol-042222-024724
Maria Chrysopoulou, Markus M Rinschen
{"title":"Metabolic Rewiring and Communication: An Integrative View of Kidney Proximal Tubule Function.","authors":"Maria Chrysopoulou, Markus M Rinschen","doi":"10.1146/annurev-physiol-042222-024724","DOIUrl":"10.1146/annurev-physiol-042222-024724","url":null,"abstract":"<p><p>The kidney proximal tubule is a key organ for human metabolism. The kidney responds to stress with altered metabolite transformation and perturbed metabolic pathways, an ultimate cause for kidney disease. Here, we review the proximal tubule's metabolic function through an integrative view of transport, metabolism, and function, and embed it in the context of metabolome-wide data-driven research. Function (filtration, transport, secretion, and reabsorption), metabolite transformation, and metabolite signaling determine kidney metabolic rewiring in disease. Energy metabolism and substrates for key metabolic pathways are orchestrated by metabolite sensors. Given the importance of renal function for the inner milieu, we also review metabolic communication routes with other organs. Exciting research opportunities exist to understand metabolic perturbation of kidney and proximal tubule function, for example, in hypertension-associated kidney disease. We argue that, based on the integrative view outlined here, kidney diseases without genetic cause should be approached scientifically as metabolic diseases.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":" ","pages":"405-427"},"PeriodicalIF":18.2,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138443609","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}
Annual review of physiologyPub Date : 2024-02-12Epub Date: 2023-11-27DOI: 10.1146/annurev-physiol-042222-025000
Charlotte A Hoogstraten, Joost G Hoenderop, Jeroen H F de Baaij
{"title":"Mitochondrial Dysfunction in Kidney Tubulopathies.","authors":"Charlotte A Hoogstraten, Joost G Hoenderop, Jeroen H F de Baaij","doi":"10.1146/annurev-physiol-042222-025000","DOIUrl":"10.1146/annurev-physiol-042222-025000","url":null,"abstract":"<p><p>Mitochondria play a key role in kidney physiology and pathology. They produce ATP to fuel energy-demanding water and solute reabsorption processes along the nephron. Moreover, mitochondria contribute to cellular health by the regulation of autophagy, (oxidative) stress responses, and apoptosis. Mitochondrial abundance is particularly high in cortical segments, including proximal and distal convoluted tubules. Dysfunction of the mitochondria has been described for tubulopathies such as Fanconi, Gitelman, and Bartter-like syndromes and renal tubular acidosis. In addition, mitochondrial cytopathies often affect renal (tubular) tissues, such as in Kearns-Sayre and Leigh syndromes. Nevertheless, the mechanisms by which mitochondrial dysfunction results in renal tubular diseases are only scarcely being explored. This review provides an overview of mitochondrial dysfunction in the development and progression of kidney tubulopathies. Furthermore, it emphasizes the need for further mechanistic investigations to identify links between mitochondrial function and renal electrolyte reabsorption.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":" ","pages":"379-403"},"PeriodicalIF":18.2,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138443610","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}
Annual review of physiologyPub Date : 2024-02-12Epub Date: 2023-11-06DOI: 10.1146/annurev-physiol-042222-022728
Elisabetta Brunello, Luca Fusi
{"title":"Regulating Striated Muscle Contraction: Through Thick and Thin.","authors":"Elisabetta Brunello, Luca Fusi","doi":"10.1146/annurev-physiol-042222-022728","DOIUrl":"10.1146/annurev-physiol-042222-022728","url":null,"abstract":"<p><p>Force generation in striated muscle is primarily controlled by structural changes in the actin-containing thin filaments triggered by an increase in intracellular calcium concentration. However, recent studies have elucidated a new class of regulatory mechanisms, based on the myosin-containing thick filament, that control the strength and speed of contraction by modulating the availability of myosin motors for the interaction with actin. This review summarizes the mechanisms of thin and thick filament activation that regulate the contractility of skeletal and cardiac muscle. A novel dual-filament paradigm of muscle regulation is emerging, in which the dynamics of force generation depends on the coordinated activation of thin and thick filaments. We highlight the interfilament signaling pathways based on titin and myosin-binding protein-C that couple thin and thick filament regulatory mechanisms. This dual-filament regulation mediates the length-dependent activation of cardiac muscle that underlies the control of the cardiac output in each heartbeat.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":" ","pages":"255-275"},"PeriodicalIF":15.7,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477420","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}
Annual review of physiologyPub Date : 2024-02-12Epub Date: 2023-10-20DOI: 10.1146/annurev-physiol-042022-030946
Xin Rui Lim, Osama F Harraz
{"title":"Mechanosensing by Vascular Endothelium.","authors":"Xin Rui Lim, Osama F Harraz","doi":"10.1146/annurev-physiol-042022-030946","DOIUrl":"10.1146/annurev-physiol-042022-030946","url":null,"abstract":"<p><p>Mechanical forces influence different cell types in our bodies. Among the earliest forces experienced in mammals is blood movement in the vascular system. Blood flow starts at the embryonic stage and ceases when the heart stops. Blood flow exposes endothelial cells (ECs) that line all blood vessels to hemodynamic forces. ECs detect these mechanical forces (mechanosensing) through mechanosensors, thus triggering physiological responses such as changes in vascular diameter. In this review, we focus on endothelial mechanosensing and on how different ion channels, receptors, and membrane structures detect forces and mediate intricate mechanotransduction responses. We further highlight that these responses often reflect collaborative efforts involving several mechanosensors and mechanotransducers. We close with a consideration of current knowledge regarding the dysregulation of endothelial mechanosensing during disease. Because hemodynamic disruptions are hallmarks of cardiovascular disease, studying endothelial mechanosensing holds great promise for advancing our understanding of vascular physiology and pathophysiology.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":" ","pages":"71-97"},"PeriodicalIF":18.2,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10922104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49673725","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}
Annual review of physiologyPub Date : 2024-02-12Epub Date: 2023-10-23DOI: 10.1146/annurev-physiol-042022-013956
Tibor Rohacs
{"title":"Phosphoinositide Regulation of TRP Channels: A Functional Overview in the Structural Era.","authors":"Tibor Rohacs","doi":"10.1146/annurev-physiol-042022-013956","DOIUrl":"10.1146/annurev-physiol-042022-013956","url":null,"abstract":"<p><p>Transient receptor potential (TRP) ion channels have diverse activation mechanisms including physical stimuli, such as high or low temperatures, and a variety of intracellular signaling molecules. Regulation by phosphoinositides and their derivatives is their only known common regulatory feature. For most TRP channels, phosphatidylinositol 4,5-bisphosphate [PI(4,5)P<sub>2</sub>] serves as a cofactor required for activity. Such dependence on PI(4,5)P<sub>2</sub> has been demonstrated for members of the TRPM subfamily and for the epithelial TRPV5 and TRPV6 channels. Intracellular TRPML channels show specific activation by PI(3,5)P<sub>2</sub>. Structural studies uncovered the PI(4,5)P<sub>2</sub> and PI(3,5)P<sub>2</sub> binding sites for these channels and shed light on the mechanism of channel opening. PI(4,5)P<sub>2</sub> regulation of TRPV1-4 as well as some TRPC channels is more complex, involving both positive and negative effects. This review discusses the functional roles of phosphoinositides in TRP channel regulation and molecular insights gained from recent cryo-electron microscopy structures.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":" ","pages":"329-355"},"PeriodicalIF":18.2,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49688439","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}
Annual review of physiologyPub Date : 2024-02-12Epub Date: 2023-11-06DOI: 10.1146/annurev-physiol-042022-014926
Duane D Hall, Hiroshi Takeshima, Long-Sheng Song
{"title":"Structure, Function, and Regulation of the Junctophilin Family.","authors":"Duane D Hall, Hiroshi Takeshima, Long-Sheng Song","doi":"10.1146/annurev-physiol-042022-014926","DOIUrl":"10.1146/annurev-physiol-042022-014926","url":null,"abstract":"<p><p>In both excitable and nonexcitable cells, diverse physiological processes are linked to different calcium microdomains within nanoscale junctions that form between the plasma membrane and endo-sarcoplasmic reticula. It is now appreciated that the junctophilin protein family is responsible for establishing, maintaining, and modulating the structure and function of these junctions. We review foundational findings from more than two decades of research that have uncovered how junctophilin-organized ultrastructural domains regulate evolutionarily conserved biological processes. We discuss what is known about the junctophilin family of proteins. Our goal is to summarize the current knowledge of junctophilin domain structure, function, and regulation and to highlight emerging avenues of research that help our understanding of the transcriptional, translational, and post-translational regulation of this gene family and its roles in health and during disease.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":" ","pages":"123-147"},"PeriodicalIF":18.2,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10922073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477421","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}