Results
- Showing results for:
- Reset all filters
Search results
-
Journal articleToe QK, Issitt T, Quinlan GJ, et al., 2026,
The Interplay Between IL-6, Hepcidin, and BMPR2 Signalling in Pulmonary Arterial Hypertension: Mechanistic Insights Into Vascular Remodelling.
, Pulm Circ, Vol: 16, ISSN: 2045-8932Pulmonary arterial hypertension (PAH) is characterized by excessive pulmonary vasoconstriction and vascular remodelling, with mutations in bone morphogenetic protein receptor type 2 (BMPR2) being the most common genetic alteration associated with the disease. While inflammatory mediators like interleukin-6 (IL-6) and the iron-regulatory hormone hepcidin have been implicated in vascular remodelling, their interaction with BMPR2 signalling remains poorly understood. This study investigated how IL-6 and hepcidin influence BMPR2 expression and downstream signalling in human pulmonary arterial endothelial cells (hPAECs). Using qPCR and Western blot analyses, we demonstrated that both IL-6 and hepcidin significantly reduced BMPR2 mRNA and protein levels in hPAECs. Intriguingly, despite this reduction, SMAD1/5 phosphorylation remained active, suggesting compensatory signalling through alternative receptor complexes. Treatment with IL-6 and hepcidin upregulated inhibitors of differentiation (ID) protein expression, mimicking the effects observed with BMPR2 knockdown. These findings reveal a novel regulatory axis involving IL-6, hepcidin, and BMPR2 in PAH pathogenesis, where IL-6 and hepcidin promote vascular remodelling through both BMPR2-dependent and independent mechanisms. These results suggest that therapeutic strategies targeting this axis, particularly those aimed at rebalancing BMP/TGF-β signalling, may hold promise for treating PAH.
-
Journal articlePaul R, Rossios C, Hinken A, et al., 2026,
IL-18 Binding Protein, a biomarker of strength maintenance after surgery but reduced physical performance in age-related sarcopenia
, PLoS ONE, Vol: 21, ISSN: 1932-6203Inflammation is thought to contribute to muscle loss in acute and chronic sarcopenia. Which inflammatory proteins contribute to sarcopenia in any condition is not clear. In a well-characterised cohort of patients experiencing acute sarcopenia following surgery, we used a proteomic screen of plasma to identify proteins associated with the change in strength. We compared change in handgrip strength over 7 days in surgery patients with plasma protein levels quantified by SOMAscan before and 24h after surgery. Surgery increased circulating concentrations of 295 proteins and decreased 301. Analysis of the day 1 protein levels showed that IL-18BP associated with maintenance of strength. To further investigate relationships between IL18BP and strength, IL-18BP as well as its ligands IL-18 and IL-37, were quantified by ELISA and in surgery patients and in 129 individuals (68 women) with age-related sarcopenia recruited to the Leucine and/or ACE inhibitor (LACE) trial. In LACE participants, the proteins were compared to grip strength, quadriceps maximal voluntary contraction (QMVC) and 6-minute walk distance (6MWD) and baseline SARC-F score. In the LACE cohort, IL-18BP was negatively associated with grip strength in men but not women, at baseline (r = −0.314, p = 0.014) and 12 months (r = −0.446, p = 0.001). QMVC and 6MWD showed similar associations. IL-18BP was associated with SARC-F in men (r = 0.389, p = 0.003) but not women. Investigation of SOMAscan data from surgery patients at baseline showed similar inverse associations of IL-18BP with strength. Comparison of circulating IL-18BP with the muscle transcriptome in these patients showed negative enrichment for mitochondrial genes. Analysis of the ligands showed that free IL-18 was proportional to 6MWD. After surgery high IL-18BP levels associate with maintenance of strength but circulating IL-18BP concentrations are associated
-
Journal articlePrak K, Luft C, Tsefou E, et al., 2026,
Functional analyses and integrated mechanisms of cellular destruction by L-amino acid oxidase
, Cell Death and Disease, Vol: 17, ISSN: 2041-4889Snakebite accidents are prevalent worldwide and cause a spectrum of severe clinical manifestations and result in a reduction of patient quality of life and economic income. A major bottleneck in envenomation treatment is our limited understanding of how venom toxins perturb specific cellular processes involved in tissue necrosis. Here, we address this knowledge gap and define the cellular mechanisms via which cell death is triggered by the snake toxin L-amino acid oxidase (LAAO). LAAO is a highly toxic enzyme present in various venoms that causes tissue necrosis, edema, coagulopathies, and organ failure. Here, we identify the residues essential for LAAO oxidation and obtain a catalytically inactive LAAO mutant, which is unable to reproduce the cellular phenotypes. Striking cellular defects are triggered by a catalysis-dependent increase in oxidative stress, via H2O2 (reaction by product). LAAO uptake by cells leads to a decrease in lysosome number and size and inhibits autophagy flux. In parallel, mitochondria function is impaired by severe proton leakage, and mitochondrial fission is stimulated, causing their engulfment by autophagosomes. However, mitochondrial clearance is prevented by the lysosomal defects. The concurrent shutdown of cell respiration and energy consumption indicates that LAAO catalysis reduces both metabolism and cell fitness. Thus, essential organelles are coordinately impaired by LAAO activity, accelerating cell demise. Considering the multi-organelle impairment, strategies to reduce organelle injury after LAAO exposure may be effective to maintain critical cell functions and strengthen adaptive responses against cytotoxicity.
-
Journal articleAlexander SPH, Fabbro D, Peach CJ, et al., 2025,
The Concise Guide to PHARMACOLOGY 2025/26: Catalytic receptors.
, Br J Pharmacol, Vol: 182 Suppl 1, Pages: S259-S306The Concise Guide to Pharmacology 2025/26 marks the seventh edition in this series of biennial publications in the British Journal of Pharmacology. Presented in landscape format, the guide provides a comparative overview of the pharmacology of drug target families. The concise nature of the Concise Guide refers to the style of presentation, being clear, accessible, and well-structured, rather than the scope of the content, which spans approximately 500 pages. The Concise Guide summarises the key pharmacological properties of around 1900 human drug targets, and nearly 7000 interactions, involving around 4400 ligands. While the content is a substantially condensed version of the more detailed information and links available at the www.guidetopharmacology.org website, the printed guide serves as a permanent, citable, point-in-time record, that remains stable despite ongoing updates to the online database. The full contents of this publication can be found at https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.70233. The Concise Guides provide expert-curated recommendations of 'Gold Standard' selective pharmacological tools, available either commercially or as donations, which enable the identification of individual drug targets or families of drug targets. While the Concise Guide offers a more streamlined overview, more comprehensive information, including detailed pharmacological profiles and links to multiple online databases, is available through the Guide to Pharmacology website. The 2025/26 edition of the Concise Guide is based on material current as of mid-2025, and supersedes all previous editions, including the 2023/24 Guide, and earlier Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), and as such provides official IUPHAR classification and nomenclature for human drug targets, where applicable. Catalytic receptors are
-
Journal articleHao Z, Leitinger B, 2025,
Warburg-Cinotti disease variant p.Tyr740Cys enhances catalytic activity of DDR2 kinase
, PLoS ONE, Vol: 20, ISSN: 1932-6203The discoidin domain receptor DDR2 is a collagen-binding receptor tyrosine kinase whose dysregulation is associated with a wide range of diseases. Missense mutations in the DDR2 kinase domain cause Warburg-Cinotti syndrome in an autosomal dominant manner. Warburg-Cinotti syndrome is a severe connective tissue disorder, characterised by a range of manifestations including joint contractures of the hand, corneal vascularisation and pannus, skin fusion and infection, keloid plaques and acro-osteolysis. The Warburg-Cinotti variants, p.Leu610Pro and p.Tyr740Cys, were previously hypothesised to cause disease through a gain-of-function mechanism but mechanistic studies addressing this notion have been lacking. Here we show that both disease variants exhibit ligand-independent constitutive autophosphorylation when expressed as full-length proteins in mammalian cells. We also characterised the enzyme kinetics of soluble WT and DDR2-Y740C kinase constructs. WT DDR2 kinase was found to follow the same two-step activation mechanism previously characterised for DDR1 kinase but with enhanced autophosphorylation and substrate phosphorylation rates. Compared with WT DDR2, DDR2-Y740C displayed further enhanced autophosphorylation and substrate phosphorylation rates, but no effect on ATP binding affinity. The increased catalytic rates of unphosphorylated DDR2-Y740C kinase were similar to those of fully phosphorylated WT DDR2, indicating that the missense variant bypasses all autoinhibitory constraints and adopts the fully active kinase conformation. Tyrosine-740 is a residue in the A-loop of DDR2 kinase that forms autoinhibitory hydrogen bonds with key catalytic residues. These hydrogen bonds cannot form in the cysteine-substituted variant, providing a structural explanation for the release of the A-loop from its autoinhibitory conformation.
-
Journal articleMarei I, Vinokurova M, Qiucheng L, et al., 2025,
Impact of type 1 diabetes on endothelial cells derived from living donors
, FASEB BioAdvances, Vol: 7, ISSN: 2573-9832Endothelial colony forming cells (ECFCs) derived from peripheral blood have been shown to retain disease phenotype in several conditions thus possessing great translational potential for regenerative medicine. Hyperglycaemia may alter the phenotype of ECFCs yet the characteristics of ECFCs isolated from people with type 1 diabetes (T1D) have not been described. Here, we establish whether ECFCs can be successfully isolated from donors with T1D and we characterize their functional properties. Human ECFCs were isolated from peripheral blood of up to 9 control and T1D donors. Expression of cell markers and cytokines was analyzed using immunocytochemistry, RT-PCR and ELISA. Ca2+ signaling and contraction were studied using Fluo-4-AM in cells treated with serial concentrations of histamine (1 × 10−7-1 × 10−4M). T1D ECFCs showed robust endothelial marker expression and displayed normal morphology but had a reduced size compared to those from control donors. In response to inflammatory stimuli, T1D ECFCs exhibited exaggerated pro-atherogenic/pro-inflammatory cytokine (IL-6 and MCP-1) and adhesion molecule gene induction (VCAM-1 and ICAM-1) but suppressed induction of interferon signaling markers (IP-10). Histamine stimulated a concentration-dependent increase in Ca2+ influx in ECFCs which was significantly reduced in ECFCs from T1D donors, independent of differences in H1 receptor expression levels. Histamine-induced contraction was significantly enhanced in T1D ECFCs. ECFCs from control and T1D donors exhibit distinct phenotypic differences redolent of the vascular pathologies associated with T1D. This establishes the utility of T1D ECFCs for modeling vascular complications but also highlights the need to understand the potential limitations of autologous ECFCs to treat diabetic complications.
-
Journal articleHaskard D, Cao J, Boyle J, et al., 2025,
Impact of an Alu insertion on the cellular localisation of tissue factor protein
, Scientific Reports, ISSN: 2045-2322 -
Journal articleWebb CM, Collins P, 2025,
Stable angina in young women
, EUROPEAN HEART JOURNAL, ISSN: 0195-668X -
Journal articleMahomed AS, Burke-Gaffney A, Moledina S, et al., 2025,
SOX17-silenced HPAECs upregulate NF-κB-induced CXCL10 and CXCL11: implications for lymphocyte chemotaxis in SOX17-PAH
, Scientific Reports, Vol: 15, ISSN: 2045-2322Pulmonary arterial hypertension (PAH) is a progressive pulmonary vasculopathy characterized by extensive pre-capillary arterial remodeling, instigating increased pulmonary vascular resistance and eventual right heart failure. Rare mutations in the SOX17 gene and common variants in the enhancer region are thought to predispose to PAH. Central to the PAH pathobiology is lung immune cell recruitment, orchestrated by the overproduction of chemokines (e.g. CXCL10) via the induction of NF-κB. Emerging evidence from murine models of SOX17 impairment suggests perivascular leukocyte accumulation in the lung, likely due to disordered inflammatory mediator expression. Therefore, in the current study we assessed the role of SOX17 deficiency in human pulmonary artery endothelial cells (HPAECs) on selected inflammatory mediator release. Following a semi-quantitative array of 100 cytokines and chemokines, we identified markedly elevated CXCL10 and CXCL11 mRNA and soluble protein release in SOX17-silenced HPAECs (versus control siRNA-treated cells), driven by excessive NF-κB p65 activity. Further, we show that plasma CXCL10 levels are raised in a small cohort (n = 3) of carriers of pathogenic SOX17 rare variants versus healthy controls. Finally, SOX17 knockdown HPAEC supernatants mediated the in vitro migration of transfectants expressing CXCR3. Therefore, enhanced lymphocyte migration may be a pathomechanism of PAH due to SOX17 loss, driven by a CXCL10/CXCL11/CXCR3 axis.
-
Journal articlePortas L, Talaei M, Dean C, et al., 2025,
Lung development genes, adult lung function and cardiovascular comorbidities
, Thorax, Vol: 80, Pages: 738-747, ISSN: 0040-6376Background: The association between lower adult lung function and increased cardiovascular comorbidity has not been adequately explained. We investigated whether shared developmental signalling pathways, critical to lung development and repair, could partly explain it.Methods: In UK Biobank (UKB), we performed pairwise colocalisation analysis of variants in 55 lung development genes associated with adult forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1)/FVC, to see if these are also associated with coronary heart disease (CHD), blood pressure (systolic, diastolic, hypertension), pulse pressure, Arterial Stiffness index and carotid intima-media thickness. For CHD, we meta-analysed data from UKB and the CARDIoGRAM consortium.Results: We found that 12 of the 55 genes shared the same variant between one (or more) lung function trait and one (or more) cardiovascular trait (H4colocalisation). The direction of effects was always in keeping with our hypothesis (lower lung function–higher cardiovascular risk) for FVC, but not always for FEV1/FVC. The seven signals for hypertension and CHD all replicated nominally in the FinnGen study, while replication was poor in the China Kadoorie Biobank (CKB) study. In addition, we found a further 10 genes where genetic associations with lung function and cardiovascular traits were within the same gene but involved different variants (H3 colocalisation). Interestingly, six of all 22 genes (H4 and H3 colocalisation) were novel for cardiovascular traits; four replicated in FinnGen, three in CKB.Conclusion: Lung function and cardiovascular traits have shared developmental pathways that may partly explain why lower lung function, especially FVC, is associated with increased cardiovascular risk.
-
Journal articleKemp PR, Griffiths M, Polkey MI, et al., 2025,
Variability in sensitivity to inflammation in muscle and lung of patients with COPD may underlie susceptibility to lung function decline
, Thorax, Vol: 80, Pages: 520-529, ISSN: 0040-6376Background: Muscle wasting and weakness (sarcopenia) are commonly associated with COPD causing frailty and reduced quality of life. The contribution of inflammation to muscle loss and the susceptibility to rapid lung function decline is debated. We hypothesised that comparing the muscle transcriptome to circulating inflammatory cytokine profiles in patients would identify any contribution of systemic inflammation to muscle atrophy.Methods: Quadriceps differential gene expression was determined between mild-COPD (n=28) and severe-COPD (n=51) using GSE100281. These microarray data were compared by biweight mid-correlation with lung function and plasma cytokine levels from the same patients.Results: Patients with severe COPD had reduced fat-free mass index (a measurement of muscle mass) compared with patients with mild COPD despite similar physical activity and inflammatory cytokine levels. Gene sets associated with inflammation and epithelial mesenchymal transition (EMT) were elevated in severe COPD, suggesting that inflammation may contribute to the loss of muscle mass. In patients with severe COPD, EMT and inflammation gene sets were strongly associated with circulating proinflammatory and anti-inflammatory cytokines. However, in patients with mild COPD, anti-inflammatory cytokines showed negative associations with these gene sets and associations with proinflammatory cytokines were weak. In data from lung and blood samples, patients with severe COPD had elevated inflammatory and EMT gene expression compared with patients with mild COPD suggesting that this phenomenon is not muscle-specific.Conclusions: In patients at the severe end of the COPD spectrum, the proinflammatory response in muscle predominates, whereas in patients at the mild end of the spectrum, the anti-inflammatory response predominates. This suggestion needs confirming in a longitudinal cohort.
-
Journal articleThomas AN, Kalakoutas A, Yates M, et al., 2025,
Mitochondrial dysfunction contributes to sustained muscle loss after cardiac surgery: a prospective observational study
, Journal of Cachexia, Sarcopenia and Muscle, Vol: 16, ISSN: 2190-5991BackgroundAs a major systemic insult, cardiac surgery can lead to significant muscle loss, which increases the time to recovery as well as being correlated with mortality. Highly variable loss of muscle mass (0%–40% rectus femoris cross-sectional area [RFcsa]) and strength in the week after surgery has aided understanding of mechanisms of sarcopenia after acute illness. To include muscle recovery, patients' muscle phenotype beyond the first week after surgery and up to their return as outpatients was studied and correlated with protein and metabolomic markers.MethodsPatients undergoing elective aortic valve surgery were recruited. Muscle mass (RFcsa), strength (handgrip, knee extension and spirometry), body composition (by bioimpedance) and health-related quality of life (generic questionnaire EQ-5D-5L) were determined pre-operatively, 7 days after surgery and at outpatient follow-up. Blood samples were taken on Days 0, 1, 3, 7 and follow-up. The plasma metabolome was determined in 20 patients at Days 0, 3, 7 and follow-up.ResultsOf 31 participants, 20 were male: mean age 68.8 years with a range between 48 and 85 years. Proportionate mean loss of RFcsa between pre-op and Day 7 values was 6.44% [95% CI 4.21 to 8.68, n = 31]; between pre-op and follow-up 9.69% [95% CI 4.92 to 14.96, n = 22]; and between Day 7 and follow-up 3.60% [95% CI −1.30 to 8.48, n = 22]. By contrast to measures of muscle bulk, the strength and functionality assessments (knee extension, handgrip, spirometry and short physical performance battery) decreased in the first week after surgery (pre-op to Day 7) followed by a return to baseline (Day 7 to follow-up). Health-related quality of life (cross-walk index) changed little over the course of the study but correlated positively at follow-up with muscle bulk (RFcsa: r = 0.58 [95% CI 0.19 to 0.81] p = 0.005) and strength of knee extension (r&thinsp
-
Conference paperBoyle J, Chiappo D, Cooper S, et al., 2025,
Aminocoumarin-based heme oxygenase activity fluorescence probe reveals novel aspects of HO-1 regulation
, 93rd Congress of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, ISSN: 0021-9150 -
Conference paperCave L, Lodge K, Chiappo D, et al., 2025,
Hemin-driven epigenetics of atherosclerotic risk gene SMARCA4 switches human blood-derived macrophages from leukocyte clearance to erythrocyte clearance
, Publisher: ELSEVIER IRELAND LTD, ISSN: 0021-9150 -
Journal articleBankole E, Wong CW, Kim S, et al., 2025,
A human PCLS model of lung injury and repair for discovery and pharmaceutical research
, Respiratory Research, Vol: 26, ISSN: 1465-9921Background: The Acid Injury and Repair (AIR) model is an ex vivo model of lung injury and repair, that was previously established using mouse precision-cut lung slices (PCLS). The AIR model provides a bridge between the current in vitro and in vivo models to study the effects of lung injury in 3D lung tissue slices. Here, we show that the AIR model can be adapted for use in human tissue as a translational model for discovery research and drug screening.Methods: To generate PCLS, resected human lung tissue was coated with alginate hydrogel to form an artificial pleura. Lung tissue was inflated by point injecting 3% agarose, followed by generation of 450-500 μM thick slices of tissue. An isolated area of each slice was injured by brief application of 0.1 M Hydrochloric acid. AIR-PCLS were then washed and cultured for 48 hr before immunostaining to assess proliferating cells (Ki67) alveolar type II/progenitor cell markers (HTII, proSP-C), Lipofibroblasts (ADRP) and endothelial cells (ERG). Viability of PCLS was assessed by both MTT assay and Live/Dead staining. Results: We show that levels of proliferation do not change in response to acid injury. However, there is a significant increase in the percentage of proSP-C and HTII positive cells in the injured regions of AIR-PCLS. We also identify non-epithelial cell populations; lipofibroblasts and endothelial cells in human AIR-PCLS, to demonstrate that other repair relevant cell types can be identified and tracked in the human AIR (hAIR model). Conclusions: The hAIR model is an effective ex-vivo tool to study early mechanisms of lung repair following injury. By establishing an area of injured tissue adjacent to uninjured tissue, this model mimics the heterogenous pattern of lung injury frequently present in lung diseases. The hAIR model will facilitate mechanistic studies of human lung repair and provides a valuable pre-clinical model for drug testing.
-
Journal articleYin X, Beele A, Theofilatos K, et al., 2025,
A Comparative Proteomics Study of Autopsy and Fresh-Frozen Coronary Artery Samples
, JOURNAL OF PROTEOME RESEARCH, Vol: 24, Pages: 3154-3159, ISSN: 1535-3893 -
Journal articleMourikis P, Benkhoff M, Wildeis L, et al., 2025,
Icosapent ethyl reduces arterial thrombosis by inhibition of cyclooxygenase-1 induced platelet reactivity
, Science Translational Medicine, Vol: 17, ISSN: 1946-6234Large, randomized trials testing omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation to reduce cardiovascular events have reported contradictory results. Interpretation of these trials is challenging, because different dosages and formulations of ω-3 PUFA were tested. Furthermore, the exact mechanisms for the reduction in cardiovascular events are unclear. In this study, we investigated the effects of ω-3 PUFA on platelet adhesion, degranulation, and aggregation in vitro and in patients with cardiovascular disease using different formulations of ω-3 PUFA. We also investigated the effects of ω-3 PUFA in rodent models of arterial thrombosis and in tail bleeding assays, including in cyclooxygenase-1 (COX-1)–deficient animals. The ω-3 PUFA eicosapentaenoic acid (EPA) dose-dependently reduced platelet adhesion, degranulation, and aggregation in vitro. Moreover, arterial thrombus formation in wild-type mice was inhibited by oral EPA administration before thrombus formation. Photoaffinity labeling and in silico docking analyses suggested a direct, competitive interaction of EPA and arachidonic acid at the level of COX-1. The COX-1 dependency of EPA’s inhibitory effects was confirmed by platelet-specific COX-1–deficient animals that had no reduction of thrombus burden by EPA. In patients with cardiovascular disease, switching from 2 grams of EPA twice daily to 1 gram of docosahexaenoic acid (DHA) (460 milligrams of EPA and 380 milligrams of DHA) once daily completely blunted the platelet inhibition achieved by EPA. Our results may partially explain contradictory results with different ω-3 PUFA formulations in clinical trials.
-
Journal articleHopkinson N, Polkey M, Price L, et al., 2025,
Dietary nitrate supplementation enhances exercise capacity in WHO Group 3 pulmonary hypertension: a double-blind, placebo-controlled, randomised crossover study (EDEN-OX2)
, Thorax, Vol: 80, Pages: 335-338, ISSN: 0040-6376Dietary nitrate supplementation, which improves skeletal muscle oxygen utilisation, vascular endothelial function and exercise capacity in people with chronic obstructive pulmonary disease, may benefit other lung conditions. In a double-blind, placebo-controlled, crossover study, in 19 adults with Group 3 pulmonary hypertension who desaturated during exercise, 140 mL of nitrate-rich beetroot juice improved endurance shuttle walk time compared with nitrate-depleted beetroot juice placebo (median (IQR) ESWT NR-BRJ 197 (140–273) s vs PL-BRJ 174 (107–229) s; median difference (MD) (95% CI) 30 (6.19 to 91.07) s, p=0.0281), endothelial function, flow-mediated dilatation (+3.40±5.47% vs −1.33±4.78; MD (95% CI) 4.73 (1.44 to 8.02), p=0.007) and lowered mean arterial blood pressure (−3.9 (−7.4 to −0.4) mm Hg, p=0.028).
-
Journal articleManolis AJ, Collins P, Lopez-Sendon J, 2025,
Diagnosing and treating stable angina: a contemporary approach for practicing physicians
, FUTURE CARDIOLOGY, Vol: 21, Pages: 291-303, ISSN: 1479-6678 -
Journal articleSagawe JS, Loake V, Openshaw P, et al., 2025,
Aging enhances pro-atrogenic gene expression and skeletal muscle loss following respiratory syncytial virus infection
, GeroScience, Vol: 47, Pages: 1485-1500, ISSN: 2509-2723Aging and many age-related health conditions are associated with skeletal muscle loss. Furthermore, older adults are more susceptible to severe respiratory infections, which can in turn lead to muscle wasting. The mechanisms by which respiratory viral infection can impact skeletal muscle in older adults are not well understood. We determined the effects of acute infection with respiratory syncytial virus (RSV) on the lung and skeletal muscle of aged mice. RSV infection caused more severe disease in aged mice with enhanced weight loss, reduced feeding, higher viral load, and greater airway inflammation. Aged but not young mice showed decreased leg muscle weight at the peak of illness and decreased size of leg muscle fibers. Aged mice increased muscle-specific expression of atrophy-promoting enzymes (Atrogin-1 and MuRF-1) and failed to increase the rate of muscle protein synthesis during RSV infection. In aged mice, the changes in Atrogin-1 and MuRF-1 gene expression in skeletal muscle correlated with IL-6 levels in the lungs. These findings indicate that RSV infection of aged mice provides a model for studying the diverse adverse systemic consequences of respiratory viral infections on health and wellbeing in older adults.
-
Journal articleWebb C, George M, Collins P, 2025,
The 2024 ESC guidelines for chronic coronary syndromes – good news for ANOCA/INOCA patients?
, European Heart Journal Open, Vol: 5, ISSN: 2752-4191 -
Journal articleLehmann M, Krishnan R, Sucre J, et al., 2025,
Precision-Cut Lung Slices: Emerging Tools for Preclinical and Translational Lung Research An Official American Thoracic Society Workshop Report
, ANNALS OF THE AMERICAN THORACIC SOCIETY, Vol: 22, Pages: 16-31, ISSN: 2329-6933- Cite
- Citations: 9
-
Journal articleDulay MS, Ahmed R, Liu A, et al., 2025,
Ascertaining the prognostic role of cardiac resynchronisation therapy in cardiac sarcoidosis: A comparison with ischaemic cardiomyopathy
, CURRENT PROBLEMS IN CARDIOLOGY, Vol: 50, ISSN: 0146-2806 -
Journal articleAhmed R, Ahsan A, Ahmed M, et al., 2024,
Outcomes of definite vs probable/presumed cardiac sarcoidosis: a systematic review and meta-analysis
, CURRENT PROBLEMS IN CARDIOLOGY, Vol: 49, ISSN: 0146-2806 -
Journal articlePhilip MA, Webb CM, Chakraborty T, et al., 2024,
Effect of sex on sodium-glucose co-transporter-2 antagonists and glucagon-like peptide-1 agonists in heart failure
, ESC Heart Failure, Vol: 11, Pages: 3539-3550, ISSN: 2055-5822BACKGROUND: Recent evidence suggests that medications not primarily targeting the cardiovascular (CV) system may have cardioprotective effects in patients with heart failure (HF), in particular the anti-diabetic therapies sodium-glucose co-transporter-2 (SGLT-2) antagonists and glucagon-like peptide-1 (GLP-1) agonists. We conducted a systematic review to assess the pooled evidence for the use of SGLT-2 antagonists and GLP-1 agonists in patients with HF and the effect of biological sex on the results. METHODS: MEDLINE, Embase, Cochrane Library and clinical trial databases were searched until February 2023. Randomized controlled trials (RCTs) published in English that included adult participants with HF who were randomized to an SGLT-2 antagonist or GLP-1 agonist with a primary or secondary outcome of HF hospitalization (HFH) or CV death were eligible for inclusion. Data pooling was undertaken using a random effects model and odds ratios (ORs) to determine the association between drug and outcome. Sub-group analyses to investigate sex differences were conducted. RESULTS: Six RCTs were included (24 781 patients). Four studies investigated SGLT-2 antagonists, and two studies examined GLP-1 agonists. SGLT-2 antagonists improved HFH {OR [95% confidence interval (CI)]: 0.69 [0.63, 0.77], P < 0.001} and CV death [0.87 (0.78, 0.97), P = 0.01] independent of diabetes status, with excellent homogeneity across all four studies. No beneficial effects were found for GLP-1 agonists. The effects of SGLT-2 antagonists on HFH and CV death were similar in men and women [OR (95% CI): HFH, 0.70 (0.64, 0.76), P < 0.001 and 0.58 (0.46, 0.74), P < 0.001, respectively; CV death, 0.86 (0.78, 0.95), P = 0.003 and 0.84 (0.73, 0.96), P = 0.01, respectively], and the neutral effect of GLP-1 agonists on HFH and CV death was similar in men and women (all P > 0.05). CONCLUSIONS: SGLT-2 antagonists but not GLP-1 a
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.