Acta Physiologica最新文献

{"title":"Keynote Lectures","authors":"","doi":"10.1111/apha.70100","DOIUrl":"https://doi.org/10.1111/apha.70100","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 S735","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012487","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}

{"title":"Table to Contents","authors":"","doi":"10.1111/apha.70107","DOIUrl":"https://doi.org/10.1111/apha.70107","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 S735","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012432","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}

{"title":"Muscle Mitochondrial Dysfunction in COPD: Beyond Oxygen Consumption","authors":"Luis Peñailillo, Sebastián Gutiérrez, Matías Monsalves-Álvarez","doi":"10.1111/apha.70097","DOIUrl":"https://doi.org/10.1111/apha.70097","url":null,"abstract":"<p>In the June issue of <i>Acta Physiologica</i>, Abdellaoui and colleagues provide a detailed examination of skeletal muscle mitochondrial dysfunction in patients with chronic obstructive pulmonary disease (COPD) and its central and peripheral physiological adaptations to endurance training [<span>1</span>]. COPD is a leading cause of morbidity and mortality worldwide, accompanied by a high economic burden and years of disability, both projected to increase to 2050 [<span>2</span>]. Skeletal muscle represents approximately 50% of body weight and represents a potent target for interventions for extra-pulmonary manifestations of COPD, such as sarcopenia, osteopenia, metabolic syndrome, and hypertension [<span>3</span>]. Thus, understanding the adaptations induced by COPD to skeletal muscle is key to investigating the potential moderating effects of these extrapulmonary manifestations. However, direct measurements of skeletal muscle mitochondrial function in humans with chronic diseases are scarce, and reports of its changes after exercise interventions are limited. Abdellaoui and colleagues demonstrate that COPD has a lower ATP synthesis rate (Figure 1A), lower oxidative phosphorylation (OXPHOS) efficiency (ATP/O ratio; Figure 1B), increased lipid peroxidation production, and higher resting proton leak (Figure 1C) compared to sedentary healthy individuals. Their research underscores the critical role of mitochondria in the pathophysiology of COPD, as matching individuals by physical activity levels allows for the exclusion of the effect of disuse on muscle function and shows that specific traits of COPD (chronic inflammation or oxidative stress) have a direct impact on mitochondrial function. This may explain the previous inverse association found between systemic inflammation (tumor necrosis factor-alpha) and maximal aerobic capacity (i.e., VO<sub>2max</sub>) in patients with moderate COPD [<span>4</span>].</p><p>The findings by Abdellaoui and colleagues bridge a gap in understanding how peripheral limitations beyond ventilatory constraints, such as mitochondrial function, contribute to exercise intolerance in COPD patients. Interestingly, the decreased maximal respiration rates with substrates like palmitoyl-carnitine and pyruvate, as well as mitochondrial complexes expression in skeletal muscle, were not rescued by endurance training (ET) in COPD. However, ET enhanced ATP synthesis rates and downregulated uncoupled respiration in COPD patients, which was not evidenced in maximal oxygen consumption (VO<sub>2max</sub>; table 2), consistent with previous studies [<span>5, 6</span>]. This highlights the importance of investigating muscle mitochondrial changes beyond the VO<sub>2max</sub> adaptations in patients with COPD. Additionally, the authors reported that mitochondrial lipid peroxidation decreased after ET in patients with COPD only, while mitochondrial protein carbonylation remained unaltered in both groups. Interestingly, mitochondrial supe","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923579","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}

{"title":"Glucose and Smooth Muscle Cells: Unraveling the Metabolic Signals Behind Vascular Calcification","authors":"Glykeria Karadimou, Ljubica Matic","doi":"10.1111/apha.70096","DOIUrl":"https://doi.org/10.1111/apha.70096","url":null,"abstract":"<p>In this issue of <i>Acta Physiologica</i>, Heuschkel et al. Present compelling evidence of the hypotaurine metabolic pathway being involved in glucose-induced vascular smooth muscle cell (SMC) calcification. Using state-of-the-art in vitro approaches, their study reveals that elevated glucose levels in SMCs promote extracellular matrix calcification, suggesting potential novel therapeutic targets for hyperglycemia-driven vascular disease [<span>1</span>].</p><p>With the global rise in type 2 diabetes (T2D) and accompanying macrovascular complications, manifestations of atherosclerosis and arterial stiffening pose major clinical challenges. Vessels of diabetic patients present increased intimal and medial calcification, which has been associated with cardiovascular events and poor outcomes [<span>2</span>]. It has been hypothesized that prevention or halted calcification can improve clinical outcomes in diabetic populations.</p><p>Vascular calcification is an active process that involves many factors such as metabolic changes, oxidative stress, inflammation, and cellular trans-differentiation. In individuals with T2D, chronic hyperglycemia accelerates this process by promoting the production of advanced glycosylation end-products, endothelial dysfunction and immune cell infiltration, creating a microenvironment that favors the osteochondrogenic transformation of SMCs within the vessel wall [<span>3</span>]. However, despite decades of research, no pharmacological therapy has been approved to prevent or reverse vascular calcification. One major challenge lies in the overlap between many of the key molecular pathways involved in vascular calcification and those in bone metabolism, posing difficulties in targeting either of them without systemic side effects. Furthermore, the vast complexity of calcification, including different types such as macro- and micro-calcification, different stages during the progression of calcification formation, and the fact that it is usually detected at an advanced irreversible stage, all indicate that it cannot be targeted uniformly. To date, no safe, specific, and effective pharmacological treatment has been validated in clinical trials, underscoring an urgent need for novel research strategies and targets in this field.</p><p>In this study, Heuschkel et al. investigate the SMC-related metabolic changes that result in calcification under hyperglycemic conditions. In the search for novel pathways and targets, they employ a multi-omics approach integrating transcriptomic and metabolomic data derived from in vitro glucose-induced calcifying SMCs. As expected, high glucose promoted calcification of SMCs. However, this was not accompanied by the upregulation of classical osteochondrogenic markers such as ALPL, RUNX2, BMP2, and SOX9, suggesting the involvement of alternative mechanisms. Through integrated analysis of transcriptomic and intra- and extra-cellular metabolomic data, the authors identified the hypotaurine met","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910350","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}

{"title":"Recent Advances in Magnesium Transport Physiology","authors":"Milos Bogdanovic, Henrik Dimke","doi":"10.1111/apha.70092","DOIUrl":"https://doi.org/10.1111/apha.70092","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897220","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}

{"title":"NMDA-Type Glutamate Receptor Activation Promotes Ischemic Arrhythmias by Targeting the AKT1–TBX3–Nav1.5 Axis","authors":"Yuxian He,&nbsp;Han Zhang,&nbsp;Qinggang Zhang,&nbsp;Zewei Sun,&nbsp;Xingang Sun,&nbsp;Ling Xia,&nbsp;Liangrong Zheng,&nbsp;Lihong Wang","doi":"10.1111/apha.70085","DOIUrl":"https://doi.org/10.1111/apha.70085","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The aim of this study is to determine the possible role of N-methyl-D-aspartate receptor (NMDAR) dysregulation in the ischemic electrical remodeling observed in patients with myocardial infarction (MI) and elucidate the underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human heart tissue was obtained from the border of the infarct and remote zones of patients with ischemic heart disease, and mouse heart tissue was obtained from the peri-infarct zone. NMDAR expression was detected using immunofluorescence (IF) and Western blotting (WB). Spontaneous ventricular arrhythmias (VAs) in mice were detected using electrocardiogram backpacks. Electrical remodeling post-MI was detected using patch clamp recordings, quantitative real-time polymerase chain reactions, IF, and WB. Mechanistic studies were performed using bioinformatic analysis, plasmid and small interfering RNA transfection, lentiviral packaging, and site-directed mutagenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NMDAR is highly expressed in patients with ischemic heart disease and mice with MI. NMDAR inhibition reduces the occurrence of VAs. Mechanistically, NMDAR activation promotes electrophysiological remodeling, as characterized by decreased Nav1.5, Kv11.1, Kv4.2, Kv7.1, Kir2.1, and Cav1.2 expression in patients with ischemic heart disease and mice with MI and rescues these ion channels dysregulation in mice with MI to varying degrees by NMDAR inhibition. Decreased Nav1.5 expression and inward sodium current density were attenuated by NMDAR inhibition in primary rat cardiomyocytes. Moreover, NMDAR activation upregulates T-Box Transcription Factor 3 (TBX3) post-translationally, further downregulating Nav1.5 transcriptionally. Furthermore, AKT1 is the predominant isoform in the ventricular myocardium upstream of TBX3 and mediates NMDAR-induced TBX3 upregulation in cardiomyocytes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>NMDAR activation contributes to MI-induced VAs by regulating the AKT1–TBX3–Nav1.5 axis, providing novel therapeutic strategies for treating ischemic arrhythmias.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885339","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}

{"title":"Magnetic Resonance Cartography of Renal Tubule Volume Fraction During Diuretic Intervention","authors":"Ehsan Tasbihi,&nbsp;Thomas Gladytz,&nbsp;Jason M. Millward,&nbsp;Kathleen Cantow,&nbsp;Erdmann Seeliger,&nbsp;Thoralf Niendorf","doi":"10.1111/apha.70095","DOIUrl":"https://doi.org/10.1111/apha.70095","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The renal tubular volume fraction (TVF) fluctuates under physiological conditions, and is altered in several renal diseases. Tools that enable noninvasive assessment of TVF are currently lacking. Magnetic Resonance (MR) TVF cartography is a novel approach for unraveling renal (patho-)physiology. Here, we employ MR-TVF cartography to monitor changes in response to the diuretic furosemide, and examine its role for the interpretation of renal oxygenation assessed by mapping the MRI relaxation time <i>T</i>₂*. We hypothesize that furosemide increases TVF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In anesthetized rats (<i>n</i> = 7) the MRI relaxation times <i>T</i>₂, <i>T</i>₂*, <i>T</i>₂′ and kidney size were obtained before/following an i.v. bolus of furosemide using a 9.4 Tesla MRI scanner. Spectral analysis of the <i>T</i>₂ signal decay was performed to estimate the number of <i>T</i>₂ components in renal tissue. TVF cartographies were calculated using voxel-wise bi-exponential fit of the <i>T</i>₂ decay. Near Infrared Spectroscopy (NIRS, <i>n</i> = 9) was used to assess the total hemoglobin concentration (HbT) as a surrogate of renal blood volume.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Furosemide induced changes in renal MRI and NIRS parameters relative to baseline: TVF_CORTEX = 31.1%, TVF_{OUTER_MEDULLA} = 30.7%, <i>T</i>_{2_CORTEX} = 13.0% and <i>T</i>_{2_OUTER_MEDULLA} = 20.6%. HbT_CORTEX was reduced by 2.7%. HbT_MEDULLA declined by 8.6%. Kidney size showed a modest increase of 2.9%. <i>T</i>₂*_{OUTER_MEDULLA} and <i>T</i>₂<b>´</b>_{OUTER_MEDULLA} rose by 20.5% and 20.2%. <i>T</i>₂*_CORTEX and <i>T</i>₂<b>´</b>_CORTEX remained unchanged. <i>T</i>₂* and TVF were strongly correlated in the outer medulla and moderately in the cortex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>MR-TVF cartography is highly relevant for elucidating mechanisms of renal (patho-)physiology, including the role of renal oxygenation assessed by MRI mapping of renal <i>T</i>₂*.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885340","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}

{"title":"Immune and Vascular Function in Cardiometabolic Disorders: Interplay With Sex Differences and Impact on Incretin Therapy","authors":"Anirudh Subramanian Muralikrishnan,&nbsp;Valentina Biasin,&nbsp;Diana Zabini,&nbsp;Elena Osto","doi":"10.1111/apha.70091","DOIUrl":"https://doi.org/10.1111/apha.70091","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Vascular dysfunction, driven by endothelial impairment, arterial stiffness, inflammation, and immune activation, contributes to cardiometabolic disorders such as hypertension and atherosclerosis. Sex differences and sex hormones influence the progression of vascular and immune dysfunction. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), regulate glucose homeostasis and also impact vascular and immuno-metabolic health. This review examines their roles in these processes, with emphasis on sex-specific effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A narrative review of preclinical and clinical studies assessing GLP-1 and GIP actions on vascular function, immune regulation, and metabolism, and their modulation by sex and sex hormones.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Incretins improve endothelial function, reduce vascular inflammation, and modulate immune-metabolic crosstalk, processes often impaired in cardiometabolic disease. Sex differences affect incretin secretion, signalling, and therapeutic responses, though underlying mechanisms remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Incretin hormones are promising targets for improving vascular and immune-metabolic health in cardiometabolic disorders. Understanding sex-specific mechanisms will be essential for optimizing incretin-based therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881187","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}

{"title":"AMPK: Accumulating Evidence in Support of its role in Dual Regulation of Vascular Function and Metabolism During Human Pregnancy","authors":"Lorna G. Moore,&nbsp;Stephanie R. Wesolowski,&nbsp;Ramón A. Lorca,&nbsp;Colleen G. Julian","doi":"10.1111/apha.70093","DOIUrl":"https://doi.org/10.1111/apha.70093","url":null,"abstract":"<div>\u0000 \u0000 <p>Adenosine monophosphate-activated protein kinase (AMPK) serves to match perfusion with metabolism. Since pregnancy necessitates significant changes in both perfusion and metabolism for supporting fetal growth, surprising is that AMPK has received scant attention during pregnancy, perhaps due to the complexity of its actions and multiple maternal, placental, and fetal targets. Here we review human as well as experimental animal studies documenting AMPK activation's broad-ranging maternal effects. Emphasized are those affecting vascular control and blood flow to the uteroplacental circulation under conditions of chronic hypoxia. Time and dosage-dependent effects on the placenta and the fetus are also reviewed, revealing that AMPK activation affects all three—maternal, placental, and fetal—pregnancy compartments. We point to the need for an integrated study of AMPK's effects in each compartment during normal as well as fetal growth-restricted (FGR) pregnancies. Since there are currently no therapies for FGR apart from early delivery, whereas there are drugs or nutritional substances activating AMPK approved for human use, such agents may represent new treatments. However, understanding their molecular mechanisms and specific actions in pregnancy compartments is required before conducting such trials.</p>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869707","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}

{"title":"The Taming of the Shrew: Making Microglia Neuroprotective by Inhibiting Cx43 Hemichannels","authors":"Yixun Su,&nbsp;Alexei Verkhratsky,&nbsp;Chenju Yi","doi":"10.1111/apha.70094","DOIUrl":"https://doi.org/10.1111/apha.70094","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869708","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}