Acta Physiologica最新文献

{"title":"Beyond the Plasma Membrane: Nuclear G Protein-Coupled Receptors With a Focus on Angiotensin Receptors","authors":"Felicitas de Tezanos Pinto,&nbsp;Wanda M. Valsecchi,&nbsp;Ornella Conte,&nbsp;Ezequiel Bruna-Haupt,&nbsp;Mariela M. Gironacci","doi":"10.1111/apha.70338","DOIUrl":"10.1111/apha.70338","url":null,"abstract":"<div>\u0000 \u0000 <p>G protein-coupled receptors (GPCRs) have traditionally been described as seven-transmembrane receptors located at the plasma membrane. However, it is now well established that these receptors can also signal from intracellular membrane compartments, including endosomes, mitochondria, the Golgi apparatus, and nuclear membranes. Importantly, such intracellular signaling can generate distinct functional outcomes even when similar G protein–mediated pathways and second messenger systems are engaged. In this context, increasing evidence indicates that angiotensin receptors, which are GPCRs, are not restricted to the cell surface but can also localize to intracellular compartments, particularly the nucleus. This intracellular distribution supports the concept of an intracrine renin–angiotensin system, in which nuclear angiotensin receptors may directly regulate gene expression and cellular function. Thus, nuclear GPCR signaling represents an additional layer of complexity in angiotensin receptor biology, extending beyond classical membrane-initiated pathways. This review focuses on nuclear angiotensin receptors, their signaling properties, and their functional relevance in regulating cellular responses.</p>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 12","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331746","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":"Can an Excised Patch Probe the Cytoplasm?","authors":"Dawon Kang","doi":"10.1111/apha.70352","DOIUrl":"10.1111/apha.70352","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 12","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331747","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":"Why Physiology Is More Relevant Than Ever","authors":"Vera Anna Kulow","doi":"10.1111/apha.70335","DOIUrl":"https://doi.org/10.1111/apha.70335","url":null,"abstract":"&lt;p&gt;At the 2026 joint annual meeting of the German Physiological Society (DPG) and the Scandinavian physiological society (SPS) congress in Hamburg, I had a talk with an invited speaker during a coffee break. He looked around the crowded hall, visibly surprised, not just by the scientific quality of the talks, but by the sheer number of attendees. “Isn't physiology kind of outdated?” he asked. “I'm honestly surprised so many people still come to a congress about something we already know everything about.”&lt;/p&gt;&lt;p&gt;His question caught me off guard, but it also made me think. Is physiology outdated? Or is this high attendance actually a sign of something else entirely?&lt;/p&gt;&lt;p&gt;The speaker's assumption reflects a common but dangerous misconception: that physiology is a “finished” science, a historical foundation we've already built upon and can now move past. According to this view, exciting work happens at the molecular level, genomics, proteomics, or single-cell sequencing, while physiology is just the old foundation, explaining things we learned decades ago. But here's the thing: we don't treat molecules. We treat patients. And patients are not collections of genes or proteins; they are integrated, complex dynamic systems.&lt;/p&gt;&lt;p&gt;What does modern physiology look like in practice? Open any recent issue of &lt;i&gt;Acta Physiologica&lt;/i&gt;, and you'll find studies that span the entire spectrum from molecule to patient. For example, Espejo and colleagues showed how the global loss of the Na&lt;sup&gt;+&lt;/sup&gt;,&lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msubsup&gt;\u0000 &lt;mi&gt;HCO&lt;/mi&gt;\u0000 &lt;mn&gt;3&lt;/mn&gt;\u0000 &lt;mo&gt;−&lt;/mo&gt;\u0000 &lt;/msubsup&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ {mathrm{HCO}}_3^{-} $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt;-cotransporter NBCn1 leads to hypertension and cardiac hypertrophy, connecting ion transport at the cellular level to whole-organ cardiovascular pathology [&lt;span&gt;1&lt;/span&gt;]. Vondenhoff et al. showed that male patients with chronic kidney disease and cardiovascular comorbidity display an immature neutrophil phenotype with reduced CD10 expression and enhanced circulating myeloperoxidase, linking altered immune cell maturation to the increased cardiovascular risk in cardiorenal disease [&lt;span&gt;2&lt;/span&gt;]. Another example is a paper from Munro et al. using super-resolution microscopy to demonstrate that neuronal ryanodine receptor 2 forms nanoscale clusters in hippocampal neurons that remodel in the APP/PS1 mouse model of Alzheimer's disease, connecting subcellular calcium channel organization to neuronal dysfunction in neurodegeneration [&lt;span&gt;3&lt;/span&gt;]. These are not historical footnotes. They are cutting-edge studies that connect molecular mechanisms to organ function, to disease, to therapy. This is physiology as it is practiced today: mechanistic, integrative, and clinically relevant.&lt;/p&gt;&lt;p&gt;But perhaps t","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 12","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70335","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149311424","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":"Resolving Hypoxia Research Controversies: An Intra-Plateau Tripartite Staging Paradigm for Chronic Mountain Sickness","authors":"Qingjia Liang,&nbsp;Haoyuan Hu,&nbsp;Wei Liu,&nbsp;Hong Mei,&nbsp;Ga Sangjia,&nbsp;Chilie Lunzhu,&nbsp;Xianwang Wang,&nbsp;Ruohan Xia","doi":"10.1111/apha.70351","DOIUrl":"https://doi.org/10.1111/apha.70351","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 12","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149311427","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 Completion Gap: Why Cardiomyocytes Enter the Cell Cycle but Rarely Complete a Division","authors":"Matheus Corteletti,&nbsp;Robson Santos,&nbsp;Yu Nie","doi":"10.1111/apha.70336","DOIUrl":"https://doi.org/10.1111/apha.70336","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 12","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149311425","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":"Peak Cardiac Mechanical and Haemodynamic Responses During Incremental Exercise Are Temporally Associated With Ventilatory Thresholds: Novel Insight Into the Coordination of Integrative Physiological Responses to Exercise","authors":"Fabian Spahiu,&nbsp;Moritz Lampkemeyer,&nbsp;Michelle Ottlik,&nbsp;Max Hagemann,&nbsp;Lars C. Helbig,&nbsp;Eric J. Stöhr","doi":"10.1111/apha.70331","DOIUrl":"https://doi.org/10.1111/apha.70331","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Maximal aerobic capacity (VO₂peak) is traditionally attributed to limitations in oxygen transport and utilization. However, it remains unclear whether peak cardiac mechanical and haemodynamic responses occur in temporal association to ventilatory thresholds during incremental exercise, and whether these relationships vary with cardiorespiratory fitness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eighteen healthy, recreationally active adults (26 ± 3.18 years VO₂peak 41.87 ± 4.76 mL·kg·min⁻¹) completed two incremental supine cycling tests to exhaustion, with breath-by-breath gas exchange analysis, exercise echocardiography, and continuous blood pressure monitoring. Plateau timing (PT) was defined as the relative heart rate (%HRmax) at which each cardiovascular variable reached its peak or plateau response. Associations between cardiovascular PTs, VO₂peak, and the first (VT1) and second ventilatory thresholds (VT2) were examined using correlation analysis. Exploratory k-means clustering was used to descriptively visualize plateau-timing distributions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>VT1 significantly correlated with PT–ejection fraction (EF) and PT–vascular conductance, whereas VT2 correlated with deformation-based parameters including PT–apical circumferential strain, PT–apical rotation, and iCarT (<i>p</i> &lt; 0.05). VO₂peak was positively associated with PT–twist and PT–apical rotation (<i>p</i> &lt; 0.05), and negatively associated with PT–EF (<i>p</i> &lt; 0.05). Exploratory clustering yielded two descriptive clusters which differed in VO₂peak (<i>p</i> &lt; 0.05) and were characterized by differences in volumetric and rotational plateau-timing distributions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>During exercise, different cardiac parameters are temporally associated with ventilatory thresholds 1 and 2. Cardiorespiratory fitness may influence interindividual differences in the temporal organization of response patterns during incremental exercise.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 12","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70331","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149311426","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":"Did You Not Get the Memo? A New PAD Model to Make Note Of","authors":"Nathanael Wood","doi":"10.1111/apha.70334","DOIUrl":"10.1111/apha.70334","url":null,"abstract":"&lt;p&gt;In a recent publication in &lt;i&gt;ACTA Physiologica&lt;/i&gt; [&lt;span&gt;1&lt;/span&gt;], Kitzerow and colleagues introduce a new model of peripheral arterial disease (PAD) that utilizes a novel intra-arterial, catheter-based approach to induce hindlimb ischemia (HLI). The new model is clinically translatable yet less technically demanding than existing HLI in vivo models and overcomes several of the previous limitations.&lt;/p&gt;&lt;p&gt;PAD currently affects over 200 million people worldwide and is usually caused by progressive build-up of fatty plaques that narrows and blocks the arteries (atherosclerosis) [&lt;span&gt;2&lt;/span&gt;]. Arterial occlusion causes a chronic reduction in blood flow, which induces ischemic myopathy of the limb muscles resulting in atrophy, fibrosis, and various other cellular, molecular, and functional skeletal muscle impairments [&lt;span&gt;2&lt;/span&gt;]. Though current medication can alleviate symptoms, there are no pharmaceutical cures of PAD. Further, it is well documented that revascularisation surgery has poor long-term durability with only short-term benefits to quality of life and, more importantly, many patients are ineligible for revascularisation surgery due to cofactors and comorbidities [&lt;span&gt;3&lt;/span&gt;]. Therefore, new treatment options are required for improving patient quality of life and outcomes. However, previous research to date has shown that observed benefits associated with many novel therapies in pre-clinical animal studies have not been consistently reproduced when translated to human trials [&lt;span&gt;4&lt;/span&gt;]. This suggests that current animal models of PAD may be limited in their clinical relevance. Improving pre-clinical animal models of PAD is imperative for increasing the likelihood of novel therapies being translatable to human patients.&lt;/p&gt;&lt;p&gt;Historically PAD models have utilized surgical ligation and complete excision of the femoral artery to induce HLI [&lt;span&gt;5&lt;/span&gt;]. While these models replicate characteristics of PAD such as skeletal muscle atrophy, fibrosis, and contractile dysfunction, the acute decrease in resting blood flow differs from the pathophysiology of PAD in humans [&lt;span&gt;6&lt;/span&gt;]. Further, damage to surrounding tissues may be unavoidable when accessing all branches of the femoral artery, affecting the physiological response to the induced ischemia.&lt;/p&gt;&lt;p&gt;The PAD Sprague–Dawley rat model developed by Kitzerow and colleagues [&lt;span&gt;1&lt;/span&gt;] addresses these issues using an ilio-femoral endovascular catheter occlusion (IFCO) method (Figure 1). Briefly, the left femoral artery is carefully exposed before performing an arteriotomy proximal to the saphenous/popliteal bifurcation into which the catheter was then inserted and secured in place with a ligature [&lt;span&gt;1&lt;/span&gt;]. This method significantly reduces resting limb perfusion for up to 28 days, as measured by laser doppler perfusion imaging, simulating a chronic ischemic response. The authors suggest this is the only Sprague–Dawley rat HLI model capable of inducing t","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 11","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70334","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149242062","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":"ITCHing To Halt Muscle Atrophy","authors":"César Vásquez-Trincado,&nbsp;Erin L. Seifert","doi":"10.1111/apha.70330","DOIUrl":"10.1111/apha.70330","url":null,"abstract":"&lt;p&gt;Skeletal muscle (SkM) mass is maintained by a coordinated balance between protein synthesis and degradation. Protein breakdown is primarily mediated by the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway [&lt;span&gt;1&lt;/span&gt;]. This balance can change during normal muscle growth or in response to resistance exercise, increasing muscle mass through hypertrophy. In contrast, nutrient deprivation, aging, muscle disuse, cancer cachexia and sustained glucocorticoid exposure (e.g., pharmacological administration of dexamethasone) can shift this balance toward net protein loss, leading to muscle atrophy, or inability to increase mass. Although increased protein breakdown may be adaptive (e.g., during fasting), sustained protein catabolism can cause muscle weakness and reduce SkM metabolic capacity. Consistent with this metabolic decline, atrophic remodeling can also compromise mitochondrial homeostasis. Short-term muscle unloading promotes atrophy alongside a reduction in markers of mitochondrial biogenesis and a molecular pattern consistent with increased mitochondrial clearance through receptor-mediated mitophagy [&lt;span&gt;2&lt;/span&gt;]. This imbalance may lower mitochondrial content and oxidative capacity in SkM.&lt;/p&gt;&lt;p&gt;Thrombospondin 1 (THBS1)—an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions—has emerged as a regulator of SkM remodeling [&lt;span&gt;3-5&lt;/span&gt;]. In the context of muscle wasting, THBS1 expression is increased under several atrophic conditions, including denervation, fasting and aging [&lt;span&gt;4&lt;/span&gt;]. Importantly, SkM-specific THBS1 overexpression induced myofiber atrophy, whereas deletion of &lt;i&gt;Thbs1&lt;/i&gt; attenuated muscle loss induced by denervation or fasting [&lt;span&gt;4&lt;/span&gt;]. Mechanistically, THBS1 promoted atrophy through TGFβ-Smad2/3-ATF4 signaling and positive modulation of the UPS and autophagy-lysosome pathway [&lt;span&gt;4&lt;/span&gt;]. These findings identify THBS1 as a major positive regulator of SkM atrophy, highlighting the importance of understanding how its expression is controlled.&lt;/p&gt;&lt;p&gt;The recent article by Yu et al. in Acta Physiologica identified ITCH (AIP4) as a regulator of THBS1 protein degradation [&lt;span&gt;6&lt;/span&gt;]. ITCH belongs to the NEDD4 family of HECT-type E3 ubiquitin ligases, previously linked to the regulation of mitochondrial morphology, cholesterol content and mitochondria-dependent apoptotic signaling [&lt;span&gt;7&lt;/span&gt;]. ITCH deficiency was also associated with impaired mitochondrial respiration and ATP production [&lt;span&gt;8&lt;/span&gt;]. Yu et al. found that dexamethasone lowered ITCH expression and increased THBS1 levels in mice and C2C12 cells. ITCH overexpression (ITCH-OE) in murine SkM attenuated dexamethasone-induced muscle loss and the expression of atrophy-related genes (atrogin-1, myostatin and MuRF-1), while improving markers of mitochondrial biogenesis, such as NRF1, TFAM and PGC-1α. THBS1-OE could override the protective effects of ITCH-OE on dexamethasone-induced atrop","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 11","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70330","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163310","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":"Sex Hormone-Binding Globulin Limits Glucocorticoid-Induced Muscle Wasting by Preserving Estrogen-Dependent Repression of Catabolic Signaling","authors":"Junyong Park,&nbsp;Ah-Young Song,&nbsp;Hae-Rahn Bae,&nbsp;Eui-Ju Hong,&nbsp;Sang R. Lee","doi":"10.1111/apha.70332","DOIUrl":"10.1111/apha.70332","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Chronic glucocorticoid (GC) therapy induces severe metabolic complications, notably secondary sarcopenia driven by excessive glucocorticoid receptor (GR)-mediated catabolism. Although sex steroids protect skeletal muscle metabolism, the role of sex hormone-binding globulin (SHBG), the primary determinant of sex steroid bioavailability, in modulating local endocrine crosstalk under GC stress remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We evaluated the clinical correlation between serum SHBG and endocrine factors in a rheumatology cohort frequently exposed to GC. To establish causality and underlying mechanisms, male and female human SHBG-transgenic (<i>hSHBG</i>-Tg) mice, with or without gonadectomy, and C2C12 myoblasts were challenged with dexamethasone (DXM) to simulate GC-induced muscle atrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In patients with high cumulative GC exposure (≥ 10,000 mg), circulating SHBG strongly inversely correlated with serum myostatin (<i>r</i> = −0.7153, <i>p</i> = 0.0076). In mice, <i>hSHBG</i>-Tg significantly rescued DXM-induced loss of muscle mass (quadriceps, gastrocnemius, tibialis anterior) and grip strength in females; notably, this protection was entirely abolished by ovariectomy. Mechanistically, <i>hSHBG</i>-Tg blunted GR Ser211 phosphorylation and downregulated the ubiquitin ligases <i>Fbxo32</i> and <i>Trim63</i>, while preserving estrogen receptor (ER) target genes (<i>Tff1</i> and <i>Pgr</i>). In vitro, estradiol antagonized DXM-induced <i>Trim63</i> transcription via ER, and co-treatment with SHBG sustained this anti-catabolic effect by extending estradiol bioavailability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SHBG acts as a promoter of estrogen bioavailability that coordinates a protective endocrine crosstalk, counteracting GR-driven catabolism in female skeletal muscle. These findings identify SHBG as a key metabolic determinant and a promising therapeutic target to prevent corticosteroid-induced muscle wasting.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 11","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163341","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":"From Inflammation Resolution to Immune Cell Fate: Maresin 2 in Hypertensive Vascular Remodeling","authors":"Lu Zhang,&nbsp;Ming-Sheng Zhou","doi":"10.1111/apha.70328","DOIUrl":"10.1111/apha.70328","url":null,"abstract":"&lt;p&gt;Inflammation is not simply terminated by the disappearance of an injurious stimulus; rather, its resolution is an active biological process coordinated by specialized pro-resolving mediators (SPMs) [&lt;span&gt;1&lt;/span&gt;]. Increasing evidence has implicated SPMs in vascular inflammation, endothelial dysfunction, and hypertension [&lt;span&gt;2, 3&lt;/span&gt;], but their potential to directly restrain vascular remodeling remains incompletely understood. In a recent issue of &lt;i&gt;Acta Physiologica&lt;/i&gt;, Peng et al. identify Maresin 2 (MaR2) as a novel regulator of hypertensive vascular remodeling and provide evidence that the actions of MaR2 extend beyond conventional suppression of inflammation [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The principal contribution of this study is the identification of a link between MaR2-mediated resolution and macrophage fibrotic plasticity. Using AngII-induced hypertension, Peng and colleagues show that MaR2 not only prevents hypertension-associated medial thickening and fibrosis but also retains efficacy when administered after hypertension has been established. Importantly, the therapeutic experiments are strengthened by the inclusion of a blood-pressure–matched hydralazine group. Despite achieving comparable blood-pressure reduction, hydralazine did not reproduce the structural and phenotypic benefits of MaR2, showing that MaR2 does not simply protect the vasculature as a consequence of lowering blood pressure, but exerts additional effects within the vascular wall. This distinction is particularly important because vascular remodeling can become partially uncoupled from hemodynamic load, and therefore normalization of blood pressure does not necessarily normalize the underlying cellular and extracellular-matrix pathology. More broadly, this finding shifts the therapeutic concept from controlling the hemodynamic trigger to modifying the biological response of the vessel wall to that trigger, an important distinction for chronic vascular disease.&lt;/p&gt;&lt;p&gt;Mechanistically, the study moves the SPM field beyond the familiar concept of cytokine suppression toward regulation of immune-cell phenotype. RNA sequencing of bone marrow-derived macrophages identified enrichment of extracellular matrix and TGF-β-related pathways, while complementary in vivo and in vitro experiments demonstrated that MaR2 reduced macrophage accumulation and acquisition of collagen-, vimentin-, and α-SMA-associated pro-fibrotic characteristics. These observations are consistent with emerging evidence that macrophage plasticity contributes to fibrotic remodeling [&lt;span&gt;5&lt;/span&gt;]. Indeed, recent single-cell, lineage-tracing, and parabiosis studies have provided evidence that circulating monocyte-derived macrophages can acquire myofibroblast-like characteristics during AngII-induced hypertensive cardiac fibrosis [&lt;span&gt;6&lt;/span&gt;]. Thus, the conceptual advance of the present study is not simply the description of macrophage-to-myofibroblast-like phenotypes, but the demonstration that a","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 11","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70328","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101403","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}