Aimi D. K. Hamilton, Johanna Hornhaver, Laura V. Sparsoe, Mads Vaarby Sorensen, Helle Praetorius
Aim
Urinary tract infections (UTIs) are common and frequently caused by uropathogenic Escherichia coli (UPEC). Whether urinary pH has any influence on the development and progression of UTIs is still widely debated. In this study, we systematically address whether urinary pH affected progression and dissemination of UTIs.
Methods
To assess the effect of urine pH on the development of UTI in vivo, 8–10-week-old female Balb/cJRj mice were randomized to 100 mM NH4Cl (acid-load), 100 mM NaHCO3 (base-load), or demineralised water as drinking water intervention 24 h before UTI was induced via installation of either UPEC or vehicle in the urinary bladder.
Results
Acid load lowered urinary pH by 0.8–1.0 pH points (p < 0.0001), decreased [HCO3−] (p = 0.0002), and increased [titratable acid] (TA, p = 0.0007), [NH4+] (p < 0.0001) and net acid concentration (NAC, p < 0.0001), while base load raised urinary pH by 0.3–0.7 pH points (p = 0.0154), increased [HCO3−] (p = 0.0358), and decreased [TA] (p = 0.0154), [NH4+] (p = 0.0121) and NAC (p = 0.0064). The UPEC infection did not affect urine acid/base parameters. Compared to control, acid load led to elevated urinary levels of tumor necrosis factor α (TNF-α), keratinocyte chemoattractant (KC), interleukin 1β (IL-1β) and IL-6, and reduced bacterial burden in urine (737.6 ± 1315.0 CFU mL−1 vs. 29.5 ± 53.3 CFU mL−1, p = 0.0030) and kidney (2.39 ± 5.94 CFU mg−1 vs. 0.06 ± 0.14 CFU mg−1, p = 0.0054). The opposite tendency was observed with base load (2204.0 ± 3135.0 CFU mL−1 urine, 2.23 ± 2.95 CFU mg−1 kidney).
Conclusion
Thus, increased urine acid excretion reduced UPEC burden in urine and decreased risk of pyelonephritis while enhancing the urinary excretion of proinflammatory cytokines.
目的：尿路感染是泌尿系致病性大肠杆菌（UPEC）引起的常见疾病。尿pH值是否对尿路感染的发生和发展有影响仍存在广泛争议。在这项研究中，我们系统地探讨了尿pH值是否影响尿路感染的进展和传播。方法：为了评估尿pH值对体内尿路感染发展的影响，8-10周龄雌性Balb/cJRj小鼠在UPEC或载具植入膀胱24小时前，随机分为100 mM NH4Cl（酸负荷）、100 mM NaHCO3（基础负荷）或去矿水作为饮用水干预。结果：酸负荷使尿pH降低0.8 ~ 1.0个pH点（p = 0.0002），使[可滴定酸]（TA, p = 0.0007）、[NH4 +] (p3 -) （p = 0.0358）升高，使[TA] （p = 0.0154）、[NH4 +] （p = 0.0121）、NAC （p = 0.0064）降低。UPEC感染对尿酸碱参数无影响。与对照组相比，酸负荷导致尿中肿瘤坏死因子α (TNF-α)、角化细胞趋化剂（KC）、白细胞介素1β (IL-1β)和IL-6水平升高，尿液（737.6±1315.0 CFU mL-1比29.5±53.3 CFU mL-1, p = 0.0030）和肾脏（2.39±5.94 CFU mg-1比0.06±0.14 CFU mg-1, p = 0.0054）细菌负荷降低。基础负荷（尿2204.0±3135.0 CFU mL-1，肾2.23±2.95 CFU mg-1）则相反。结论：尿酸排泄量增加可减轻尿中upc负担，降低肾盂肾炎风险，同时促进尿中促炎细胞因子的分泌。
{"title":"Oral Acid Load Lowers Bacterial Burden and Elevates Urinary Proinflammatory Response in a Mouse Model of Urinary Tract Infection","authors":"Aimi D. K. Hamilton, Johanna Hornhaver, Laura V. Sparsoe, Mads Vaarby Sorensen, Helle Praetorius","doi":"10.1111/apha.70149","DOIUrl":"10.1111/apha.70149","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Urinary tract infections (UTIs) are common and frequently caused by uropathogenic <i>Escherichia coli</i> (UPEC). Whether urinary pH has any influence on the development and progression of UTIs is still widely debated. In this study, we systematically address whether urinary pH affected progression and dissemination of UTIs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To assess the effect of urine pH on the development of UTI in vivo, 8–10-week-old female Balb/cJRj mice were randomized to 100 mM NH<sub>4</sub>Cl (acid-load), 100 mM NaHCO<sub>3</sub> (base-load), or demineralised water as drinking water intervention 24 h before UTI was induced via installation of either UPEC or vehicle in the urinary bladder.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Acid load lowered urinary pH by 0.8–1.0 pH points (<i>p</i> < 0.0001), decreased [HCO<sub>3</sub><sup>−</sup>] (<i>p</i> = 0.0002), and increased [titratable acid] (TA, <i>p</i> = 0.0007), [NH<sub>4</sub><sup>+</sup>] (<i>p</i> < 0.0001) and net acid concentration (NAC, <i>p</i> < 0.0001), while base load raised urinary pH by 0.3–0.7 pH points (<i>p</i> = 0.0154), increased [HCO<sub>3</sub><sup>−</sup>] (<i>p</i> = 0.0358), and decreased [TA] (<i>p</i> = 0.0154), [NH<sub>4</sub><sup>+</sup>] (<i>p</i> = 0.0121) and NAC (<i>p</i> = 0.0064). The UPEC infection did not affect urine acid/base parameters. Compared to control, acid load led to elevated urinary levels of tumor necrosis factor α (TNF-α), keratinocyte chemoattractant (KC), interleukin 1β (IL-1β) and IL-6, and reduced bacterial burden in urine (737.6 ± 1315.0 CFU mL<sup>−1</sup> vs. 29.5 ± 53.3 CFU mL<sup>−1</sup>, <i>p</i> = 0.0030) and kidney (2.39 ± 5.94 CFU mg<sup>−1</sup> vs. 0.06 ± 0.14 CFU mg<sup>−1</sup>, <i>p</i> = 0.0054). The opposite tendency was observed with base load (2204.0 ± 3135.0 CFU mL<sup>−1</sup> urine, 2.23 ± 2.95 CFU mg<sup>−1</sup> kidney).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Thus, increased urine acid excretion reduced UPEC burden in urine and decreased risk of pyelonephritis while enhancing the urinary excretion of proinflammatory cytokines.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909444","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}
Sensory gating is a neurological mechanism that filters out irrelevant sensory input, protecting cognitive processing from sensory overload. Patients with schizophrenia usually lack sensory gating, which severely affects normal cognitive functions due to an overload of irrelevant information. Sensory gating and cognitive tasks have been found to need moderate activity in the medial prefrontal cortex (mPFC). However, the specific control mechanisms of the mPFC remain unknown. We assume that the “Excitation-Inhibition” imbalance in the mPFC can induce schizophrenia-like sensory gating and cognitive defects.
Methods
The current study utilized chemogenetics and FloxP-Cre techniques to examine the distinct roles of glutamatergic and GABAergic neurons in the mPFC in regulating sensory gating and cognitive functions, both in healthy and schizophrenia-like mouse models.
Results
Manipulation of neural activity in the mPFC, specifically inhibiting GABAergic neurons or stimulating glutamatergic neurons in the mPFC, caused schizophrenia-like sensory gating deficits, disturbances in temporal order and long-term recognition memory, and hyperlocomotion. Conversely, activating GABAergic neurons or inhibiting glutamatergic neurons mitigated these schizophrenia-like symptoms, including sensory gating deficits, temporal order memory impairments, and hyperlocomotion.
Conclusions
We discovered that a disturbance in the “Excitation-Inhibition” balance in the mPFC significantly contributes to schizophrenia-like sensory gating deficits, cognitive impairments, and hyperlocomotion. Remarkably, correcting this imbalance in schizophrenia-like mice alleviated these deficits, providing profound insights into the regulatory functions of glutamatergic and GABAergic neurons in the mPFC.
{"title":"Chemogenetic Restoration of the “Excitation-Inhibition” Imbalance in the Medial Prefrontal Cortex Ameliorates Schizophrenia-Like Sensory Gating Deficits","authors":"Xiaoyu Chen, Lichun He, Qiuxia Zhang, Yanci Luo, Yushan Cao, Huifeng Zhu, Weihai Chen","doi":"10.1111/apha.70151","DOIUrl":"10.1111/apha.70151","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Sensory gating is a neurological mechanism that filters out irrelevant sensory input, protecting cognitive processing from sensory overload. Patients with schizophrenia usually lack sensory gating, which severely affects normal cognitive functions due to an overload of irrelevant information. Sensory gating and cognitive tasks have been found to need moderate activity in the medial prefrontal cortex (mPFC). However, the specific control mechanisms of the mPFC remain unknown. We assume that the “Excitation-Inhibition” imbalance in the mPFC can induce schizophrenia-like sensory gating and cognitive defects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The current study utilized chemogenetics and FloxP-Cre techniques to examine the distinct roles of glutamatergic and GABAergic neurons in the mPFC in regulating sensory gating and cognitive functions, both in healthy and schizophrenia-like mouse models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Manipulation of neural activity in the mPFC, specifically inhibiting GABAergic neurons or stimulating glutamatergic neurons in the mPFC, caused schizophrenia-like sensory gating deficits, disturbances in temporal order and long-term recognition memory, and hyperlocomotion. Conversely, activating GABAergic neurons or inhibiting glutamatergic neurons mitigated these schizophrenia-like symptoms, including sensory gating deficits, temporal order memory impairments, and hyperlocomotion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We discovered that a disturbance in the “Excitation-Inhibition” balance in the mPFC significantly contributes to schizophrenia-like sensory gating deficits, cognitive impairments, and hyperlocomotion. Remarkably, correcting this imbalance in schizophrenia-like mice alleviated these deficits, providing profound insights into the regulatory functions of glutamatergic and GABAergic neurons in the mPFC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898687","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}
<p>Collagen-VI has long waited in the wings of cardiac biology. Better known to neuromuscular researchers who study Ullrich congenital muscular dystrophy and Bethlem myopathy [<span>1</span>], this beaded filament collagen is often relegated to the diffuse background of the ventricular wall, grouped with generic “fibrotic” matrix rather than treated as a molecule with specific, testable roles in mechanics and signaling. The study by Krstic and colleagues in this issue invites a re-evaluation of that view [<span>2</span>]. By deleting the Col6a1 gene in rat and interrogating the heart from organ to myofilament scale, they reveal collagen-VI as a determinant of systolic performance and Ca<sup>2+</sup> handling and a potential player in arrhythmogenesis.</p><p>The central finding is paradoxical in the best physiological sense. In vivo, Col6a1-deficient rats show reduced cardiac ejection fraction, fractional shortening, stroke volume and output, consistent with impaired systolic function. Yet isolated Col6a1-null ventricular myocytes exhibit larger Ca<sup>2+</sup> transients and increased sarcoplasmic reticulum Ca<sup>2+</sup> load—changes that usually support stronger, not weaker, twitch force. Resolution comes at the tissue level: trabeculae from null rats generate less peak stress and display slower twitch kinetics, indicating that the major defect lies in force transmission rather than in activating Ca<sup>2+</sup>. Collagen-VI therefore appears not just as a passive constituent of the extracellular-space but as part of the mechanical line coupling intracellular contraction to chamber-level pumping.</p><p>This picture dovetails with earlier work on collagen-VI in myocardial infarction, where global deletion improved post-MI remodeling with less fibrosis and better-preserved ventricular function [<span>3, 4</span>]. These findings cast collagen-VI not as a neutral scaffold but as a driver of adverse fibrotic remodeling, aligning with broader views that highlight fibroblast–matrix signaling as a therapeutic target [<span>5</span>]. Krstic et al. now add that in the uninjured rat heart, the same gene deletion exacts a cost—baseline systolic depression and heightened susceptibility to triggered activity under β-adrenergic stress—so that collagen-VI emerges as a double-edged molecule, harmful in excess yet required in proper amounts for efficient force transmission and stable excitation–contraction coupling.</p><p>The calcium findings are particularly informative. Despite unchanged T-tubule regularity and RyR2 cluster architecture by confocal and STED imaging, Col6a1-deficient cardiomyocytes exhibit increased Ca<sup>2+</sup> transient amplitude and greater SR Ca<sup>2+</sup> content, as revealed by caffeine-evoked release. Under β-adrenergic stimulation, the difference is amplified: isoproterenol elicits larger transients, faster upstrokes, and, in about half of Col6a1-null myocytes, spontaneous diastolic Ca<sup>2+</sup> release events absent in wild-
{"title":"Untethered and Triggered: Collagen VI Loss at the Nexus of Force, Fibrosis, and Arrhythmia","authors":"Robert G. Gourdie","doi":"10.1111/apha.70155","DOIUrl":"10.1111/apha.70155","url":null,"abstract":"<p>Collagen-VI has long waited in the wings of cardiac biology. Better known to neuromuscular researchers who study Ullrich congenital muscular dystrophy and Bethlem myopathy [<span>1</span>], this beaded filament collagen is often relegated to the diffuse background of the ventricular wall, grouped with generic “fibrotic” matrix rather than treated as a molecule with specific, testable roles in mechanics and signaling. The study by Krstic and colleagues in this issue invites a re-evaluation of that view [<span>2</span>]. By deleting the Col6a1 gene in rat and interrogating the heart from organ to myofilament scale, they reveal collagen-VI as a determinant of systolic performance and Ca<sup>2+</sup> handling and a potential player in arrhythmogenesis.</p><p>The central finding is paradoxical in the best physiological sense. In vivo, Col6a1-deficient rats show reduced cardiac ejection fraction, fractional shortening, stroke volume and output, consistent with impaired systolic function. Yet isolated Col6a1-null ventricular myocytes exhibit larger Ca<sup>2+</sup> transients and increased sarcoplasmic reticulum Ca<sup>2+</sup> load—changes that usually support stronger, not weaker, twitch force. Resolution comes at the tissue level: trabeculae from null rats generate less peak stress and display slower twitch kinetics, indicating that the major defect lies in force transmission rather than in activating Ca<sup>2+</sup>. Collagen-VI therefore appears not just as a passive constituent of the extracellular-space but as part of the mechanical line coupling intracellular contraction to chamber-level pumping.</p><p>This picture dovetails with earlier work on collagen-VI in myocardial infarction, where global deletion improved post-MI remodeling with less fibrosis and better-preserved ventricular function [<span>3, 4</span>]. These findings cast collagen-VI not as a neutral scaffold but as a driver of adverse fibrotic remodeling, aligning with broader views that highlight fibroblast–matrix signaling as a therapeutic target [<span>5</span>]. Krstic et al. now add that in the uninjured rat heart, the same gene deletion exacts a cost—baseline systolic depression and heightened susceptibility to triggered activity under β-adrenergic stress—so that collagen-VI emerges as a double-edged molecule, harmful in excess yet required in proper amounts for efficient force transmission and stable excitation–contraction coupling.</p><p>The calcium findings are particularly informative. Despite unchanged T-tubule regularity and RyR2 cluster architecture by confocal and STED imaging, Col6a1-deficient cardiomyocytes exhibit increased Ca<sup>2+</sup> transient amplitude and greater SR Ca<sup>2+</sup> content, as revealed by caffeine-evoked release. Under β-adrenergic stimulation, the difference is amplified: isoproterenol elicits larger transients, faster upstrokes, and, in about half of Col6a1-null myocytes, spontaneous diastolic Ca<sup>2+</sup> release events absent in wild-","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877327","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}
Ependymal cell-derived perilesional glial borders may play a beneficial role in neural regeneration after spinal cord injury (SCI). Yes-associated protein (YAP), a key transcriptional cofactor, is involved in the control of body organ size by regulating cell differentiation, proliferation, growth, and apoptosis; however, it remains unclear whether the roles and underlying mechanisms of YAP signaling regulate the ependymal cell-derived perilesional glial borders after SCI.
Methods
We established a dorsal cord incision injury mouse model. The YAPf/f; FoxJ1-CreERT2 (YAPFoxJ1-ERT2-CKO) mice and YAPf/f; FoxJ1-CreERT2; Rosa26tdTomato mice were generated to examine the roles of ependymal YAP signaling in SCI. The RNA-seq, western blot, immunostaining, and cell-fate tracing tools were used to investigate the underlying mechanisms of YAP signaling in the regulation of ependymal cell-derived perilesional glial borders after SCI.
Results
YAP was activated in ependymal cells after SCI. Interestingly, YAP deletion in ependymal cells (YAPFoxJ1-ERT2-CKO mice) aggravated the neuronal loss and impaired the formation of perilesional glial borders and then inhibited the functional recovery after SCI. Furthermore, YAP deletion inhibited the proliferation and differentiation of ependymal cells to astrocytes and oligodendrocytes and reduced the secretion of neurotrophic factors after SCI. Mechanically, RNA-seq revealed that the expression of Colorectal Neoplasia Differentially Expressed (CRNDE) was downregulated in YAPFoxJ1-ERT2-CKO mice. Furthermore, we found downregulation of P300 and β-catenin and upregulation of GSK-3β in YAP−/− ependymal cells after SCI.
Conclusion
Ependymal YAP signaling promotes the formation of ependymal cell-derived perilesional glial borders in mice through the P300-CRNDE-Wnt/β-catenin pathway after SCI, which provides a novel target for SCI.
{"title":"Ependymal Yes-Associated Protein Promotes the Neural Regeneration Through Enhancing the Ependymal Cell-Derived Perilesional Glial Borders in Mice After Spinal Cord Injury","authors":"Jiashu Lian, Xiaowu Lin, Jiali Shi, Mengxian Jia, Wenbin Zhang, Xin Yan, Sheng Lu, Dewei Xie, Jian Zhou, Zhoule Zhu, Ziwei Fan, Yaozhi He, Yumin Wu, Jianhong Dong, Wei Zhang, Kelun Huang, Minyu Zhu, Ying Wang, Zhihui Huang, Honglin Teng","doi":"10.1111/apha.70147","DOIUrl":"10.1111/apha.70147","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Ependymal cell-derived perilesional glial borders may play a beneficial role in neural regeneration after spinal cord injury (SCI). Yes-associated protein (YAP), a key transcriptional cofactor, is involved in the control of body organ size by regulating cell differentiation, proliferation, growth, and apoptosis; however, it remains unclear whether the roles and underlying mechanisms of YAP signaling regulate the ependymal cell-derived perilesional glial borders after SCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We established a dorsal cord incision injury mouse model. The YAP<sup>f/f</sup>; FoxJ1-CreERT2 (YAP<sup>FoxJ1-ERT2</sup>-CKO) mice and YAP<sup>f/f</sup>; FoxJ1-CreERT2; Rosa26<sup>tdTomato</sup> mice were generated to examine the roles of ependymal YAP signaling in SCI. The RNA-seq, western blot, immunostaining, and cell-fate tracing tools were used to investigate the underlying mechanisms of YAP signaling in the regulation of ependymal cell-derived perilesional glial borders after SCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>YAP was activated in ependymal cells after SCI. Interestingly, YAP deletion in ependymal cells (YAP<sup>FoxJ1-ERT2</sup>-CKO mice) aggravated the neuronal loss and impaired the formation of perilesional glial borders and then inhibited the functional recovery after SCI. Furthermore, YAP deletion inhibited the proliferation and differentiation of ependymal cells to astrocytes and oligodendrocytes and reduced the secretion of neurotrophic factors after SCI. Mechanically, RNA-seq revealed that the expression of Colorectal Neoplasia Differentially Expressed (CRNDE) was downregulated in YAP<sup>FoxJ1-ERT2</sup>-CKO mice. Furthermore, we found downregulation of P300 and β-catenin and upregulation of GSK-3β in YAP<sup>−/−</sup> ependymal cells after SCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Ependymal YAP signaling promotes the formation of ependymal cell-derived perilesional glial borders in mice through the P300-CRNDE-Wnt/β-catenin pathway after SCI, which provides a novel target for SCI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843296","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":"A Hundred Years of the Chemosensory Synapse: A Tribute to Fernando de Castro","authors":"Fernando de Castro, José López-Barneo","doi":"10.1111/apha.70145","DOIUrl":"10.1111/apha.70145","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145814665","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}
A. Krstic, H. Moammer, S. Hassan, J. Bai, P. Kallingappa, Y. Hou, M. Annandale, A. Taberner, J.-C. Han, K. Mellor, M. L. Ward, C. J. Barrett, D. J. Crossman
Aim
Collagen VI has recently been strongly linked to poor outcomes in heart failure through increased endotrophin, a collagen VI-derived signaling molecule linked to fibrotic remodeling in cardiovascular disease. The mutation of collagen VI can result in Ullrich congenital muscular dystrophy and Bethlem myopathy, pointing to a critical function in muscle physiology. However, the functional role of collagen VI in the heart is poorly understood. In human heart failure with reduced ejection fraction, collagen VI is increased within the remodeled T-tubules, suggesting a possible role in tubular structure and Ca2+ dynamics.
Methods
To investigate this hypothesis, a global knockout of the collagen VI alpha 1 gene (Col6a1−/−) was generated in the rat.
Results
T-tubule structure and ryanodine receptor cluster organization were unchanged, but echocardiography demonstrated reduced systolic function. Consistent with this, isolated trabeculae from Col6a1−/− hearts generated significantly less peak stress, confirming impaired contractile force at the tissue level. Paradoxically, isolated cardiomyocytes from the Col6a1−/− rat had increased Ca2+ transient amplitude and increased sarcoplasmic reticulum Ca2+ load that would be expected to increase force. β-adrenergic stimulation further increased Ca2+ transient amplitude and was associated with diastolic Ca2+ release events in Col6a1−/− cardiomyocytes. Furthermore, β-adrenergic stimulation of Col6a1−/− trabeculae exhibited spontaneous contractions, indicating an increased susceptibility to arrhythmic activity.
Conclusion
Together, these results indicate collagen VI has a role in both force transduction and Ca2+ cycling in the heart.
{"title":"The Absence of Collagen VI Reduces Systolic Function but Paradoxically Increases Ca2+ Release in the Rat Heart","authors":"A. Krstic, H. Moammer, S. Hassan, J. Bai, P. Kallingappa, Y. Hou, M. Annandale, A. Taberner, J.-C. Han, K. Mellor, M. L. Ward, C. J. Barrett, D. J. Crossman","doi":"10.1111/apha.70144","DOIUrl":"10.1111/apha.70144","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Collagen VI has recently been strongly linked to poor outcomes in heart failure through increased endotrophin, a collagen VI-derived signaling molecule linked to fibrotic remodeling in cardiovascular disease. The mutation of collagen VI can result in Ullrich congenital muscular dystrophy and Bethlem myopathy, pointing to a critical function in muscle physiology. However, the functional role of collagen VI in the heart is poorly understood. In human heart failure with reduced ejection fraction, collagen VI is increased within the remodeled T-tubules, suggesting a possible role in tubular structure and Ca<sup>2+</sup> dynamics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To investigate this hypothesis, a global knockout of the collagen VI alpha 1 gene (Col6a1<sup>−/−</sup>) was generated in the rat.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>T-tubule structure and ryanodine receptor cluster organization were unchanged, but echocardiography demonstrated reduced systolic function. Consistent with this, isolated trabeculae from Col6a1<sup>−/−</sup> hearts generated significantly less peak stress, confirming impaired contractile force at the tissue level. Paradoxically, isolated cardiomyocytes from the Col6a1<sup>−/−</sup> rat had increased Ca<sup>2+</sup> transient amplitude and increased sarcoplasmic reticulum Ca<sup>2+</sup> load that would be expected to increase force. β-adrenergic stimulation further increased Ca<sup>2+</sup> transient amplitude and was associated with diastolic Ca<sup>2+</sup> release events in Col6a1<sup>−/−</sup> cardiomyocytes. Furthermore, β-adrenergic stimulation of Col6a1<sup>−/−</sup> trabeculae exhibited spontaneous contractions, indicating an increased susceptibility to arrhythmic activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Together, these results indicate collagen VI has a role in both force transduction and Ca<sup>2+</sup> cycling in the heart.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802775","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}
Manovriti Thakur, Thibaut Quillard, Nico Angliker, Mark Siegrist, Yvonne Jansen, Yi Yan, Julia Wollenhaupt, Claudia Goettsch, Lars Maegdefessel, Nadia Sachs, Marc Schindewolf, Drosos Kotelis, Heidi Noels, Yvonne Döring
Aim
Lower-extremity arterial disease (LEAD) is a manifestation of atherosclerotic cardiovascular disease, affecting 230 million people worldwide with increasing prevalence. Medial arterial calcification (MAC) is common in LEAD patients and contributes to disease-related mortality. However, therapeutic strategies targeting femoral MAC are lacking, and its underlying mechanisms remain unclear. This study aimed to identify molecular drivers of femoral MAC in LEAD.
Methods & Results
Calcium deposits and pro-calcifying markers were analyzed in human patient samples using von Kossa staining, immunofluorescence, and gene expression analysis. Femorals showed significantly more calcification and pro-calcifying gene expression than carotids. Given MAC abundance in LEAD, we assessed medial calcification in Apoe−/− mice fed a WD for 4/21 weeks. Digital PCR revealed upregulation of Ddr1 and Bmp2 in femoral versus carotid arteries after 21 weeks of WD. DDR1 expression positively correlated with calcification in human femoral samples. In vitro experiments with mouse femoral vs. carotid vascular smooth muscle cells (VSMCs) confirmed a significantly higher prevalence of calcifying proteins (DDR1, BMP2, and RUNX2) in femoral VSMCs. Additionally, calcification analyses in murine and human VSMCs showed that DDR1 inhibition reduced, while DDR1 activation increased, calcium deposition. Transcriptomic analysis revealed elevated NF-κB expression in human femoral arteries, matching data in femoral VSMCs. DDR1 stimulation activated NF-κB, and its inhibition blocked DDR1-induced calcification.
Conclusion
This study identifies DDR1 as a key driver of calcification in LEAD, operating through NF-κB activation and the expression of calcifying proteins. Targeting DDR1 may offer a novel therapeutic approach to prevent MAC in LEAD.
{"title":"DDR1 Regulates Femoral Arterial Calcification in Lower-Extremity Artery Disease Through NF-Kappa B Activation","authors":"Manovriti Thakur, Thibaut Quillard, Nico Angliker, Mark Siegrist, Yvonne Jansen, Yi Yan, Julia Wollenhaupt, Claudia Goettsch, Lars Maegdefessel, Nadia Sachs, Marc Schindewolf, Drosos Kotelis, Heidi Noels, Yvonne Döring","doi":"10.1111/apha.70146","DOIUrl":"10.1111/apha.70146","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Lower-extremity arterial disease (LEAD) is a manifestation of atherosclerotic cardiovascular disease, affecting 230 million people worldwide with increasing prevalence. Medial arterial calcification (MAC) is common in LEAD patients and contributes to disease-related mortality. However, therapeutic strategies targeting femoral MAC are lacking, and its underlying mechanisms remain unclear. This study aimed to identify molecular drivers of femoral MAC in LEAD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods & Results</h3>\u0000 \u0000 <p>Calcium deposits and pro-calcifying markers were analyzed in human patient samples using von Kossa staining, immunofluorescence, and gene expression analysis. Femorals showed significantly more calcification and pro-calcifying gene expression than carotids. Given MAC abundance in LEAD, we assessed medial calcification in <i>Apoe−/−</i> mice fed a WD for 4/21 weeks. Digital PCR revealed upregulation of <i>Ddr1</i> and <i>Bmp2</i> in femoral versus carotid arteries after 21 weeks of WD. DDR1 expression positively correlated with calcification in human femoral samples. In vitro experiments with mouse femoral vs. carotid vascular smooth muscle cells (VSMCs) confirmed a significantly higher prevalence of calcifying proteins (DDR1, BMP2, and RUNX2) in femoral VSMCs. Additionally, calcification analyses in murine and human VSMCs showed that DDR1 inhibition reduced, while DDR1 activation increased, calcium deposition. Transcriptomic analysis revealed elevated NF-κB expression in human femoral arteries, matching data in femoral VSMCs. DDR1 stimulation activated NF-κB, and its inhibition blocked DDR1-induced calcification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study identifies DDR1 as a key driver of calcification in LEAD, operating through NF-κB activation and the expression of calcifying proteins. Targeting DDR1 may offer a novel therapeutic approach to prevent MAC in LEAD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12706703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761683","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}
Andrea Tognozzi, Fabrizia Carli, Sherif Abdelkarim, Sara Cornuti, Francesca Damiani, Maria Grazia Giuliano, Alice Miniati, Martina Nasisi, Lia De Benedictis, Kousha Changizi Ashtiani, Gaia Scabia, Margherita Maffei, Pierre Baldi, Amalia Gastaldelli, Paola Tognini
Aim
Obesity significantly impacts the central nervous system (CNS), increasing the risks of neuropsychiatric disorders and dementia. Intermittent fasting (IF) shows promise for improving peripheral and CNS health, but its mechanisms are unclear.
Methods
Using a diet-induced obesity mouse model [10 weeks high fat diet (HFD), then 4 weeks intervention], we compared HFD, HFD-IF, ad libitum control chow (CC), and CC-IF groups.
Results
Switching to CC or IF reduced body weight, fat mass, and improved glucose tolerance. Notably, CC-IF uniquely enhanced exploration and reduced anxiety-like behavior. Transcriptomics revealed HFD-induced hippocampal neuroinflammation, whereas metabolomics identified a specific succinate signature in CC-IF mice: plasma concentration decreased, whereas liver and brown adipose tissue (BAT) levels increased. Succinate supplementation mimicked CC-IF metabolic and behavioral benefits and reduced hippocampal inflammation.
Conclusion
These findings suggest that regulating plasma succinate and its metabolism in liver and BAT may represent a novel biochemical correlate underlying the metabolic, neuroinflammatory, and behavioral improvements induced by IF.
{"title":"Succinate Modulation as a Biochemical Correlate of Metabolic and Neurobehavioral Changes Associated With Intermittent Fasting in Obesity","authors":"Andrea Tognozzi, Fabrizia Carli, Sherif Abdelkarim, Sara Cornuti, Francesca Damiani, Maria Grazia Giuliano, Alice Miniati, Martina Nasisi, Lia De Benedictis, Kousha Changizi Ashtiani, Gaia Scabia, Margherita Maffei, Pierre Baldi, Amalia Gastaldelli, Paola Tognini","doi":"10.1111/apha.70143","DOIUrl":"10.1111/apha.70143","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Obesity significantly impacts the central nervous system (CNS), increasing the risks of neuropsychiatric disorders and dementia. Intermittent fasting (IF) shows promise for improving peripheral and CNS health, but its mechanisms are unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using a diet-induced obesity mouse model [10 weeks high fat diet (HFD), then 4 weeks intervention], we compared HFD, HFD-IF, ad libitum control chow (CC), and CC-IF groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Switching to CC or IF reduced body weight, fat mass, and improved glucose tolerance. Notably, CC-IF uniquely enhanced exploration and reduced anxiety-like behavior. Transcriptomics revealed HFD-induced hippocampal neuroinflammation, whereas metabolomics identified a specific succinate signature in CC-IF mice: plasma concentration decreased, whereas liver and brown adipose tissue (BAT) levels increased. Succinate supplementation mimicked CC-IF metabolic and behavioral benefits and reduced hippocampal inflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that regulating plasma succinate and its metabolism in liver and BAT may represent a novel biochemical correlate underlying the metabolic, neuroinflammatory, and behavioral improvements induced by IF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754952","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}
We have previously described an important role of skeletal muscle tone in body temperature regulation, muscle tone defined as the tonic motor unit activity recorded between movements. Here, we study muscle tone in an extensive sample of new muscles outside (external muscles) and inside (internal muscles) the body core.
Methods
Skeletal muscles of adult, male Wistar rats were chronically implanted with EMG electrodes, and EMG was recorded during exposures to changes in ambient temperatures between 30°C and 5°C. Every consecutive period between movements (M) was identified as one of rest (R), whether the rat was awake or asleep. The amount of tonic motor unit impulse activity, or muscle tone, within (R) was then measured by root mean square analysis of the raw EMG.
Results
Muscle tone in external muscles depended strictly on ambient temperature, rising and falling with falling and rising ambient temperatures. In contrast, muscle tone in internal iliacus and psoas muscles showed no relation to ambient temperature but increased markedly during recovery from hypothermia caused by general anesthesia. Mean tonic motor unit firing rates varied between 10 and 75 Hz.
Conclusion
All examined muscles, except iliopsoas, participated in moment-to-moment regulation of body temperature by heat-producing muscle tone during rest. Iliopsoas appeared to have an emergency function coming into play when the body temperature fell below some critical value, as during anesthesia. The wide range of tonic firing rates indicated that not only slow but also fast, fatigue-resistant motor units contributed to heat-producing muscle tone during rest.
{"title":"Body Temperature Regulation in the Rat by Muscle Tone","authors":"Arild Njå, Terje Lømo","doi":"10.1111/apha.70148","DOIUrl":"10.1111/apha.70148","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We have previously described an important role of skeletal muscle tone in body temperature regulation, muscle tone defined as the tonic motor unit activity recorded between movements. Here, we study muscle tone in an extensive sample of new muscles outside (external muscles) and inside (internal muscles) the body core.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Skeletal muscles of adult, male Wistar rats were chronically implanted with EMG electrodes, and EMG was recorded during exposures to changes in ambient temperatures between 30°C and 5°C. Every consecutive period between movements (M) was identified as one of rest (R), whether the rat was awake or asleep. The amount of tonic motor unit impulse activity, or muscle tone, within (R) was then measured by root mean square analysis of the raw EMG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Muscle tone in external muscles depended strictly on ambient temperature, rising and falling with falling and rising ambient temperatures. In contrast, muscle tone in internal iliacus and psoas muscles showed no relation to ambient temperature but increased markedly during recovery from hypothermia caused by general anesthesia. Mean tonic motor unit firing rates varied between 10 and 75 Hz.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>All examined muscles, except iliopsoas, participated in moment-to-moment regulation of body temperature by heat-producing muscle tone during rest. Iliopsoas appeared to have an emergency function coming into play when the body temperature fell below some critical value, as during anesthesia. The wide range of tonic firing rates indicated that not only slow but also fast, fatigue-resistant motor units contributed to heat-producing muscle tone during rest.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12704031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754922","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}
The mechanism of pulmonary venous remodeling (PVR) remains unclear. We tested the role of the calcium sensing receptor (CaSR) in PVR in pulmonary hypertension (PH).
Methods
PVR was investigated in two PH models, monocrotaline (MCT)-induced PH (MCT-PH) and hypoxia-induced PH (HPH). Human pulmonary venous smooth muscle cells (PVSMCs) were subjected to hypoxia. We examined whether CaSR is involved in the enhanced Ca2+ influx and proliferation in PVSMCs and whether CaSR mediates PVR.
Results
PVR presented in distal pulmonary veins (PV) in MCT-PH and HPH rats, accompanied by upregulated CaSR expression in PVSMCs from PH rats. Hypoxia promoted human PVSMCs proliferation with increased CaSR and HIF-1α expression in hypoxic cells. Extracellular Ca2+ restoration induced a huge increase in [Ca2+]i in MCT-PH PVSMCs and human hypoxic PVSMCs, which was significantly higher than that in normal cells. Both the basal [Ca2+]i and proliferate rate in MCT-PH PVSMCs and human hypoxic PVSMCs were higher than in normal PVSMCs. Spermine or R568 enhanced, whereas both NPS2143 or NPS2390 and siCaSR attenuated the extracellular Ca2+-induced [Ca2+]i increase in rat MCT-PH PVSMCs and human hypoxic PVSMCs and hypoxia-induced human PVSMCs proliferation. Blockade of CaSR with NPS2143 attenuated the increases in basal [Ca2+]i in PVSMCs, right ventricular systolic pressure, and Fulton index in PH rats and prevented PVR and PH development in rats injected with MCT or exposed to hypoxia.
Conclusions
Upregulated CaSR mediating excessive PVSMCs proliferation through enhanced CaSR function and increased intracellular Ca2+ signaling is an important pathogenic mechanism underlying the development of PVR in PH.
{"title":"Upregulated Calcium Sensing Receptor Mediates Pulmonary Venous Remodeling in Pulmonary Hypertension","authors":"Qiudi Mo, Xing Wen, Luyao Wang, Weitao Cao, Jieping Liang, Shaoxing Li, Zhenli Fu, Xiaohua Gao, Yan Xue, Hong Yuan, Zhenbo Xu, Wei Hong, Yumin Zhou, Gongyong Peng","doi":"10.1111/apha.70142","DOIUrl":"10.1111/apha.70142","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The mechanism of pulmonary venous remodeling (PVR) remains unclear. We tested the role of the calcium sensing receptor (CaSR) in PVR in pulmonary hypertension (PH).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PVR was investigated in two PH models, monocrotaline (MCT)-induced PH (MCT-PH) and hypoxia-induced PH (HPH). Human pulmonary venous smooth muscle cells (PVSMCs) were subjected to hypoxia. We examined whether CaSR is involved in the enhanced Ca<sup>2+</sup> influx and proliferation in PVSMCs and whether CaSR mediates PVR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PVR presented in distal pulmonary veins (PV) in MCT-PH and HPH rats, accompanied by upregulated CaSR expression in PVSMCs from PH rats. Hypoxia promoted human PVSMCs proliferation with increased CaSR and HIF-1α expression in hypoxic cells. Extracellular Ca<sup>2+</sup> restoration induced a huge increase in [Ca<sup>2+</sup>]<sub>i</sub> in MCT-PH PVSMCs and human hypoxic PVSMCs, which was significantly higher than that in normal cells. Both the basal [Ca<sup>2+</sup>]<sub>i</sub> and proliferate rate in MCT-PH PVSMCs and human hypoxic PVSMCs were higher than in normal PVSMCs. Spermine or R568 enhanced, whereas both NPS2143 or NPS2390 and siCaSR attenuated the extracellular Ca<sup>2+</sup>-induced [Ca<sup>2+</sup>]<sub>i</sub> increase in rat MCT-PH PVSMCs and human hypoxic PVSMCs and hypoxia-induced human PVSMCs proliferation. Blockade of CaSR with NPS2143 attenuated the increases in basal [Ca<sup>2+</sup>]<sub>i</sub> in PVSMCs, right ventricular systolic pressure, and Fulton index in PH rats and prevented PVR and PH development in rats injected with MCT or exposed to hypoxia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Upregulated CaSR mediating excessive PVSMCs proliferation through enhanced CaSR function and increased intracellular Ca<sup>2+</sup> signaling is an important pathogenic mechanism underlying the development of PVR in PH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740062","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号