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PLoS One. 2025 Jun 25;20(6):e0326249. doi: 10.1371/journal.pone.0326249. eCollection 2025.

ABSTRACT

Low cardiorespiratory fitness (CRF) is a well-established risk factor for cardiovascular disease (CVD) and all-cause mortality. Since CRF is largely genetically determined, understanding the genetic influences on CRF might reveal the protective mechanisms of high CRF. One gene found to be associated with CRF is COX7A2L. COX7A2L is a mitochondrial supercomplex assembly factor, but its role in cellular metabolism remains a topic of discussion. We hypothesized that COX7A2L could play a role in cellular respiration in cardiomyocytes, affecting cardiac function and CRF. To determine the effect of COX7A2L on cardiomyocyte function, we overexpressed and knocked down COX7A2L in human AC16 cardiomyocytes and performed MTT assays and Seahorse XF Cell Mito Stress Tests to assess cell viability and mitochondrial function. For the mitochondrial function measurements, we stimulated the cells with isoproterenol to investigate if the effect of altering COX7A2L levels would be larger under simulated increased energy demand. Overexpression and knockdown were validated using sandwich ELISA. Our findings showed that altering COX7A2L expression in human AC16 cardiomyocytes did not significantly affect cell viability or mitochondrial function. Further research is necessary to determine whether COX7A2L influences cardiomyocyte function and CRF.

PMID:40560843 | PMC:PMC12194157 | DOI:10.1371/journal.pone.0326249

Am J Physiol Cell Physiol. 2025 Jun 25. doi: 10.1152/ajpcell.01006.2024. Online ahead of print.

ABSTRACT

Aberrant autophagy mediated by AMPK/mTOR/ULK1 pathway (a canonical autophagy pathway) plays important roles in diabetic cardiomyopathy (DCM). Asprosin (ASP) secreted by white adipose tissue involves in systemic metabolism disorders. However, its role in DCM remains poorly understood. Therefore, the purpose of this study was to investigate its roles and underlying mechanism in the DCM from the perspective of autophagy and apoptosis. In the in vivo experiments, we observed the effects of ASP-deficiency (ASP-/-) or ASP intervention on cardiac function, fibrosis, autophagy and apoptosis in a diabetes mellitus (DM) mouse model induced by high-fat feeding and streptozotocin (STZ) injection; in the in vitro experiments, we evaluated the effects of ASP intervention with or without 3-MA (autophagy inhibitor) or siAMPK in a H9c2 model injured by high glucose (HG). Our results show that ASP intervention attenuates the myocardial injury induced by DM (P<0.05) and HG (P<0.05). Additionally, the autophagy level markedly increases (P<0.05) in diabetic mice and ASP-deficiency worsens the increase induced by DM (P<0.05). In contrast, ASP intervention alleviates over-autophagy induced by DM (P<0.05) or HG (P<0.05). Mechanistically, the protective effect of ASP against myocardial injury is through inhibiting the over-autophagy mediated by AMPK/mTOR/ULK1 pathway (P<0.05). Taken together, the findings suggest that ASP would be a potential therapeutic target and the recombinant ASP might be a promising candidate to treat metabolism-associated CVD. Although the findings would present a promise for the treatment of DCM, it is worth noting that the mouse model used fails to fully mimic the human DCM pathophysiology.

PMID:40560772 | DOI:10.1152/ajpcell.01006.2024

BMJ Open. 2025 Jun 25;15(6):e100553. doi: 10.1136/bmjopen-2025-100553.

ABSTRACT

INTRODUCTION: Ischaemia-reperfusion (I/R) injury remains a major challenge in heart transplantation, with mortality risk increasing significantly when allograft ischaemic time exceeds 4 hours. Non-ischaemic heart preservation (NIHP), using continuous hypothermic perfusion, has shown promise in preliminary studies for reducing I/R injury and improving outcomes. This randomised controlled trial aims to compare NIHP with standard static cold storage (SCS) in adult heart transplantation.

METHODS AND ANALYSIS: The trial is a prospective, open-label, multicentre, single-blinded, randomised controlled trial including 66 adult heart transplant recipients across four Swedish hospitals. Participants will be randomised into 1:1 ratio to NIHP or SCS preservation groups and undergo a 12-month follow-up period. The primary outcome is 1-year survival free from acute cellular rejection or retransplantation. Secondary outcomes include quality of life, I/R injury markers, graft function and adverse events. Substudies will evaluate renal function using MRI and continuously monitor physical activity and heart rhythm via wearable devices. Analysis will follow intention-to-treat principles, with time-to-event analysis using Cox proportional hazard models and Kaplan-Meier estimates.

ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethical Review Authority. It will be conducted according to the Declaration of Helsinki and relevant local and international regulations. Results will be published in peer-reviewed journals following Consolidated Standards of Reporting Trials guidelines.

TRIAL REGISTRATION NUMBER: NCT04066127.

PMID:40562558 | PMC:PMC12198846 | DOI:10.1136/bmjopen-2025-100553

Rev Esp Cardiol (Engl Ed). 2025 Jun 23:S1885-5857(25)00190-2. doi: 10.1016/j.rec.2025.04.011. Online ahead of print.

ABSTRACT

Introduction and objectives This report presents updated data on heart transplants in Spain, including procedures carried out in 2024. It reviews trends over the past decade (2015-2024) in donor and recipient characteristics, surgical techniques, immunosuppression strategies, and survival rates. Methods Data were drawn from the Spanish heart transplant registry, which is updated annually. The analysis includes 347 transplants performed in 2024, as well as procedures from 2015 to 2023 (n = 2721). Results In 2024, the number of heart transplants increased by 6.8% compared with 2023. There were no significant changes in recipient age or sex, but the proportion of urgent transplants rose to 47.0%. Use of circulatory support devices increased, particularly extracorporeal membrane oxygenation. The average donor age showed a slight increase in 2024, although the long-term trend remained downward. Donation after circulatory death accounted for 29.1% of transplants in 2024. One-year survival rates improved, reaching 85.2% for transplants performed between 2021 and 2023. Conclusions The number of heart transplants continued to grow, nearing historic highs, largely due to the expansion of donation after circulatory death. Improved 1-year survival reflects the maturity of transplant programs, advances in surgical and medical management, and better pretransplant conditions in recipients. Full English text available from: www.revespcardiol.org/en.

PMID:40562161 | DOI:10.1016/j.rec.2025.04.011

J Card Fail. 2025 Jun 23:S1071-9164(25)00284-2. doi: 10.1016/j.cardfail.2025.05.017. Online ahead of print.

ABSTRACT

BACKGROUND: Cytomegalovirus (CMV) infection post heart transplantation (HT) is associated with worse outcomes. Antiviral prophylaxis for at-risk patients is standard of care. Valganciclovir, the most commonly used antiviral, is associated with significant adverse events, particularly leukopenia. Letermovir is a CMV-specific anti-viral with a favorable side effect profile but its efficacy in HT recipients is unclear. This study aims to assess the safety and efficacy of letermovir for CMV prophylaxis in HT recipients.

METHODS: This single-center retrospective analysis included HT recipients at our center from January 2020-September 2023. Patients who were switched to letermovir for CMV prophylaxis for leukopenia/neutropenia on valganciclovir, and 1) remained on letermovir for at least 60 days or 2) developed CMV viremia on letermovir within 60 days of initiation were included. Primary endpoint was incidence of CMV viremia/disease during letermovir therapy. Secondary endpoints included changes in white blood cell (WBC) count, tacrolimus dosing, and clinically significant acute rejection.

RESULTS: Fifty-two patients received letermovir for an average of 8.2 months (range 1 to 35 months). Average time from transplant to letermovir initiation was 9.2 months, (range 0.9 to 77 months). Eight (15.4%) patients developed breakthrough CMV viremia on letermovir with a median viral load of 205 [IQR 142-367.5] copies/mL, and 4 of these patients were converted back to valganciclovir; overall 92.3% of patients completed therapy with letermovir. There were no episodes of suspected or biopsy-proven, CMV disease. Majority of patients (78%) required dose reductions of tacrolimus following letermovir initiation with no episodes of tacrolimus toxicity requiring hospitalization. WBC counts increased, on average, from 2.6 to 5.3 × 103 cells/μL, p <0.001.

CONCLUSIONS: Letermovir holds promise as an effective and safe alternative to valganciclovir for CMV prophylaxis in HT recipients.

PMID:40562091 | DOI:10.1016/j.cardfail.2025.05.017

J Clin Oncol. 2025 Jun 25:JCO2402477. doi: 10.1200/JCO-24-02477. Online ahead of print.

ABSTRACT

In REACH3 (ClinicalTrials.gov identifier: NCT03112603), ruxolitinib was investigated versus best available therapy (BAT) for 3 years in patients with steroid-refractory/dependent chronic graft-versus-host-disease (SR/D-cGVHD). Patients received ruxolitinib (10 mg twice daily) or BAT for 24 weeks; thereafter (weeks 24-156), patients continued randomized treatment, entered long-term survival follow-up, or crossed over from BAT to ruxolitinib. In 329 randomly assigned patients (ruxolitinib: 165; BAT: 164), the median failure-free survival (FFS) was 38.4 months for ruxolitinib versus 5.7 months for BAT (hazard ratio, 0.36 [95% CI, 0.27 to 0.49]). Median duration of response (DOR) was not reached for ruxolitinib versus 6.4 months for BAT. Ruxolitinib-treated patients had a higher probability of FFS (ruxolitinib: 56.5%; BAT: 18.2%) and maintaining a response (ruxolitinib: 59.6%; BAT: 26.7%) at 36 months. Median overall survival was not reached. Nonrelapse mortality and malignancy relapse/recurrence events were low. In 70 patients who crossed over to ruxolitinib, the overall response rate (50.0%) at week 24 and best overall response (81.4%) during the crossover period were consistent with the primary analysis of randomly assigned patients. No new safety signals were observed. Ruxolitinib provided longer FFS and DOR than BAT, demonstrating sustained efficacy and manageable safety over 3 years of follow-up in patients with SR/D-cGVHD.

PMID:40561385 | DOI:10.1200/JCO-24-02477

Eur Heart J Qual Care Clin Outcomes. 2025 Jun 25:qcaf052. doi: 10.1093/ehjqcco/qcaf052. Online ahead of print.

ABSTRACT

There is increasing recognition that social determinants of health affect outcomes in individuals with congenital heart disease and cause health disparities. This scientific statement from the European Association of Preventive Cardiology of the European Society of Cardiology provides an outline of the existing disparities from a global perspective in this population. We review the current knowledge on racial and ethnic patterns and the role of deprivation status, food insecurity, built environment, financial strain, psychological health and parental distress and education and literacy in creating inequities. Finally, we provide future directions for policy, research and clinical practice in achieving health equity in the congenital heart disease population.

PMID:40561137 | DOI:10.1093/ehjqcco/qcaf052

Transplantation. 2025 Jun 24. doi: 10.1097/TP.0000000000005435. Online ahead of print.

ABSTRACT

The rising prevalence of heart failure, global donor heart shortages, and limitations of current assist devices have driven innovation in bioartificial hearts (BAHs) and cardiac constructs. This systematic review aims to give an overview of new developments in BAHs, engineered myocardium, and biohybrid ventricular assist devices research, evaluating their clinical readiness and outcomes while addressing strengths and limitations. Significant variability in study designs and outcomes highlights both advancements and ongoing challenges in this field. Although the development of BAHs and larger cardiac tissue constructs remains in preclinical stages, progress has been achieved in the development of cardiac patches, with 2 approved for clinical use. Several critical challenges continue to hinder the successful clinical translation of bioengineered cardiac solutions. Achieving meaningful myocardial contraction remains a complex task, as well as ensuring adequate vascularization and electrical integration. Biocompatibility limits the progression of bioengineered cardiac constructs toward clinical applications. Innovations in 3-dimensional bioprinting, shape-memory materials, adhesives, microfabrication techniques, and soft and stretchable bioelectronics are driving advancements in this field. However, outcomes regarding hemodynamic performance of BAHs or constructs are marginal at best. Cardiac patches show promising results in preclinical studies, with the paracrine effect of the patches being the most plausible explanation of these results. Importantly, from very little clinical experience thus far, we cannot conclude that cardiac patches have any beneficial effects nor that they are safe. The path toward developing a fully functional BAH or even parts of a functional myocardium appears to be long, complex, and perhaps even unattainable.

PMID:40561089 | DOI:10.1097/TP.0000000000005435

Cell Transplant. 2025 Jan-Dec;34:9636897251348566. doi: 10.1177/09636897251348566. Epub 2025 Jun 25.

ABSTRACT

Mesenchymal stem cells (MSCs) are considered to be effective treatments for various diseases, and a wide variety of clinical studies have been performed worldwide. However, substantial obstacles remain before they can be approved and disseminated as treatments. A major bottleneck is the elucidation of their mechanisms of action, and the molecules that are essential for their efficacy have not been fully characterized. In this paper, I review the studies that attempted to identify the key mediators of MSCs that are involved in their effects on disease using in vivo models. More specifically, studies are discussed in which reductions in the efficacy of MSCs in animal models of disease were induced by the absence of key mediators. The target diseases were lung, joint, cerebral nerve, or cardiac diseases and graft-versus-host disease (GVHD). The following molecules were identified and are discussed herein: TSG-6, VEGF, KGF, HGF, claudin-4, ANXA1, MANF, PYCR1, integrin β1, PDGFRβ, type-II collagen, CD151, TIMP3, TGF-β1, BDNF, COX-2, Botch, IL-1β, CTRP3, CXCR4, miR-34c, FSTL1, IDO, iNOS, IFNγR1, PGES, Chi3l1, and IL-6. These are key mediators of the efficacy of MSCs in vivo.

PMID:40560652 | PMC:PMC12198582 | DOI:10.1177/09636897251348566

JACC Cardiovasc Interv. 2025 Jun 23;18(12):1526-1537. doi: 10.1016/j.jcin.2025.04.041.

ABSTRACT

BACKGROUND: Transcatheter patent foramen ovale (PFO) closure has become the gold-standard treatment for patients with cryptogenic embolism and PFO, but long-term outcomes data are limited.

OBJECTIVES: The aim of this study was to report the extended clinical outcomes of patients who underwent transcatheter PFO closure for cryptogenic embolism.

METHODS: PROLONG (PFO Transcatheter Occlusion Long-Term Outcomes National Group) is an investigator-initiated, multicenter, retrospective registry that enrolled patients who underwent transcatheter PFO closure between 1999 and 2013 at 12 centers in Italy. This analysis included only patients who underwent PFO closure for cryptogenic embolism, defined as cryptogenic ischemic stroke, transient ischemic attack, systemic embolism, or silent ischemic lesions on magnetic resonance imaging. Clinical, imaging, procedural, and follow-up data were collected from electronic health records and telephone interviews.

RESULTS: The study included 1,245 patients (mean age 47 ± 12 years, 56% women), with a mean follow-up duration of 14.5 ± 2.4 years. During follow-up, 34 patients (2.7%) experienced recurrent ischemic stroke, transient ischemic attack, or systemic embolism (0.19 per 100 patient-years). Predictors of recurrent events were Risk of Paradoxical Embolism (RoPE) score ≤ 7 (HR: 3.44; 95% CI: 1.06-11.3; P = 0.041), nonprobable PFO-Associated Stroke Causal Likelihood (PASCAL) classification (HR: 2.72; 95% CI: 1.17-6.34; P = 0.020), and new-onset atrial fibrillation (HR: 7.01; 95% CI: 2.45-20.1; P < 0.001). Serious complications were rare (0.4% in hospital, 0.4% during follow-up) and nonfatal.

CONCLUSIONS: This study confirms the long-term efficacy and safety of transcatheter PFO closure for patients with cryptogenic embolism and PFO in a real-world setting. (PFO Transcatheter Occlusion Long-Term Outcomes National Group [PROLONG] Registry; NCT06504121).

PMID:40562467 | DOI:10.1016/j.jcin.2025.04.041

Crit Care Explor. 2025 Jun 25;7(7):e1281. doi: 10.1097/CCE.0000000000001281. eCollection 2025 Jul 1.

ABSTRACT

OBJECTIVES: Acidemia frequently evolves in pediatric critical care patients, especially with congenital heart defects. Worsening acidemia secondary to inadequate systemic oxygen delivery can be detrimental to patients' outcomes and the ability to predict it has the potential to prompt early interventions to improve the clinical state. We aimed to evaluate the association of a novel near real-time predictive analytics algorithm with acidemia (ACD) (arterial pH < 7.25) in pediatric patients admitted to a critical care unit.

STUDY DESIGN: Retrospective observational study in nine tertiary institutions in the United States.

SETTING: Majority of patients were admitted to the cardiac ICU. Using Etiometry platform data (Etiometry, Boston, MA), acidemia (ACD) index was validated.

PATIENTS: Patients 12 years old or younger were admitted to an ICU between February 1, 2018, and November 31, 2020.

INTERVENTION: A total of 24,431 arterial blood pH measurements from 1858 patients were included in the validation dataset. The ACD index was calculated using a physiologic algorithm that incorporates patients' variables including laboratory and clinical data. Based on the previous assessment of the physiologic state of the patient, the physiologic algorithm interprets the new data in a real-time manner using Bayes' theorem.

MEASUREMENT AND MAIN RESULTS: Based on a complete dataset, the area under the receiver operating characteristic curve of the ACD index was 0.93. As the index value increased, the likelihood of having acidemia increased (p < 0.01). The relative risk of having acidemia when the ACD index is less than 1 was 0.11 (95% CI, 0.07-0.15), and the relative risk of not having acidemia when the ACD index was greater than 99 was 0.38 (95% CI, 0.32-0.46).

CONCLUSIONS: In this large pediatric cohort, higher ACD index values were associated with a higher likelihood of having acidemia. Consequently, this novel index has the potential to identify severe changes in clinical status. Prospective analysis of the ACD index is important to understand its utility in the management of pediatric critical illness.

PMID:40561190 | PMC:PMC12200221 | DOI:10.1097/CCE.0000000000001281

Eur Heart J Qual Care Clin Outcomes. 2025 Jun 25:qcaf052. doi: 10.1093/ehjqcco/qcaf052. Online ahead of print.

ABSTRACT

There is increasing recognition that social determinants of health affect outcomes in individuals with congenital heart disease and cause health disparities. This scientific statement from the European Association of Preventive Cardiology of the European Society of Cardiology provides an outline of the existing disparities from a global perspective in this population. We review the current knowledge on racial and ethnic patterns and the role of deprivation status, food insecurity, built environment, financial strain, psychological health and parental distress and education and literacy in creating inequities. Finally, we provide future directions for policy, research and clinical practice in achieving health equity in the congenital heart disease population.

PMID:40561137 | DOI:10.1093/ehjqcco/qcaf052

JACC Cardiovasc Interv. 2025 Jun 23;18(12):1540-1553. doi: 10.1016/j.jcin.2025.03.036.

ABSTRACT

BACKGROUND: In women with severe aortic stenosis, there are limited data regarding outcome differences following transcatheter (TAVR) vs surgical aortic valve replacement (SAVR).

OBJECTIVES: The authors sought to examine outcomes of TAVR vs SAVR in a patient-level pooled analysis of women in the RHEIA and PARTNER 3 trials.

METHODS: Patients in both trials were randomly allocated to a balloon-expandable SAPIEN 3/Ultra valve or to surgical bioprostheses. Individual patient data of female participants in the 2 trials were pooled. The primary endpoint was all-cause mortality, all stroke, or rehospitalization at 1 year.

RESULTS: A total of 376 women were randomized to TAVR and 336 to SAVR. The mean age was ∼73 years, and the mean Society of Thoracic Surgeons (STS) score was 2.1%. Kaplan-Meier estimates of event rates at 1 year with TAVR vs SAVR were 8.5% vs 16.8% for the composite of all-cause mortality, all stroke, or rehospitalization (absolute difference -8.2%; 95% CI: -13.1% to -3.3%; P < 0.001), 1.1% vs 2.1% (P = 0.27) for all-cause mortality, 2.7% vs 3.9% (P = 0.35) for all stroke, and 5.4% vs 11.9% (P = 0.002) for rehospitalization. The composite endpoint of all-cause death or stroke was similar between the 2 treatment groups: 3.5% vs 5.4% (absolute difference -1.9%; 95% CI: -5.0% to 1.1%; P = 0.21).

CONCLUSIONS: Among women with symptomatic severe aortic stenosis, TAVR led to a reduction in the rate of the combined endpoint of all-cause mortality, stroke, or rehospitalization at 1-year follow-up, largely due to a significant reduction in the rate of rehospitalization.

PMID:40562469 | DOI:10.1016/j.jcin.2025.03.036

Clin Pract. 2025 May 30;15(6):106. doi: 10.3390/clinpract15060106.

ABSTRACT

BACKGROUND/AIM: The aim of this study was to determine predictors of major adverse cardiovascular events, including MACE (mortality, non-fatal recurrent infarction, non-fatal stroke, and target vessel revascularization-TVR) in stable post-STEMI patients.

METHOD: We analyzed STEMI patients without cardiogenic shock at admission included in our STEMI Register. The patients were treated with primary PCI. The follow-up period was eight years.

RESULTS: From 1 December 2006 to 31 December 2016, a total of 3079 patients were included in the Register. In the first year, MACE was registered in 348 (11.3%) patients. The remaining patients were considered stable. They were included in further analysis. At eight years, the rates were as follows: MACE 3.9%, non-fatal recurrent infarction 2.1%, TVR 1.8%, non-fatal stroke 0.5%, and mortality 2.1%. Predictors for 8-year MACE were age >60 years (60-69 vs. <60 years HR 1.65; 70-79 vs. <60 years HR 1.82; ≥80 vs. <60 years HR 3.16), EF < 50% (EF 40-49% HR 2.38; EF < 40% HR 2.32), diabetes mellitus (HR 1.49), and 3-vessel coronary artery disease (HR 1.44).

CONCLUSIONS: Four predictors identified stable post-STEMI patients who remained at a higher risk for the occurrence of MACE. Stable post-STEMI patients with one or more of these risk factors may require more aggressive secondary prevention measures or a personalized approach to improve their prognosis.

PMID:40558224 | PMC:PMC12192057 | DOI:10.3390/clinpract15060106

Cells. 2025 Jun 10;14(12):875. doi: 10.3390/cells14120875.

ABSTRACT

The adult human heart has a limited ability to regenerate after injury, leading to the formation of fibrotic scars and a subsequent loss of function. In fish, mice, and humans, cardiac remodeling after myocardial injury involves the activation of epicardial and endocardial cells, pericytes, stem cells, and fibroblasts. The heart's extracellular matrix (ECM) plays a significant role in the regeneration and recovery process. The epicardium, endocardium, and pericytes reactivate the embryonic program in response to ECM stimulation, which leads to epithelial-mesenchymal transition, cell migration, and differentiation. This review analyzes the role of ECM in guiding the differentiation or dedifferentiation and proliferation of heart components by comparing significant findings in a zebrafish model with those of mammals.

PMID:40558502 | PMC:PMC12191243 | DOI:10.3390/cells14120875

JACC Asia. 2025 Jun 2:S2772-3747(25)00265-0. doi: 10.1016/j.jacasi.2025.04.008. Online ahead of print.

ABSTRACT

BACKGROUND: Lower socioeconomic status, intelligence, and cognition are linked to a higher likelihood of atrial fibrillation (AF). However, whether these factors directly cause AF or whether others mediate this relationship is unclear.

OBJECTIVES: Our study aimed to determine the causal link between lower socioeconomic status, intelligence, cognition, and AF, and identify mediators.

METHODS: We conducted a 2-sample Mendelian randomization analysis with data from European ancestry genome-wide association studies. Genetic instruments for education, intelligence, cognition, income, and occupation (n = 248,847-1,131,881) evaluated their relationship with AF (FinnGen study: 50,743 cases and 210,652 control subjects; 6 European studies: 60,620 and 970,216).

RESULTS: The pooled results from meta-analysis combining data from 2 studies indicated that education, intelligence, and cognition were causally associated with AF (P < 0.05). Genetically predicted, each 1-SD increase in educational attainment was associated with a 19% decreased risk of AF (OR: 0.81; 95% CI: 0.71-0.92), independent of intelligence and cognition. Among 44 candidate mediators, 8 factors were identified to mediate the education-AF association, including heart failure (mediation proportion: 95.35%), body fat mass (44.05%), waist circumference (42.93%), coronary heart disease (30.1%), body mass index (29.0%), myocardial infarction (28.8%), diastolic blood pressure (21.7%), and waist-to-hip ratio (14.3%).

CONCLUSIONS: Our study suggests that education exerts a causal and protective effect against AF, independent of intelligence and cognition. Heart failure, obesity, and ischemic heart disease serve as mediating factors in the pathway from education to AF, underscoring the importance of considering these conditions in preventing AF associated with education inequality.

PMID:40560110 | DOI:10.1016/j.jacasi.2025.04.008

Adv Sci (Weinh). 2025 Jun 25:e00096. doi: 10.1002/advs.202500096. Online ahead of print.

ABSTRACT

Pulmonary vascular remodeling, which current therapeutic targets fail to alleviate disease severity, plays a key role in pulmonary arterial hypertension (PAH). Irisin is identified as a protective factor involved in regulating inflammation and oxidative stress, but its role in PAH remains unknown. To investigate, plasma irisin levels and its local pulmonary artery expression are measured in patients with PAH and mouse models. Irisin expression is significantly decreased in patients with PAH and PAH mouse models. Furthermore, overexpression and exogenous injection of irisin effectively alleviate hemodynamic and right-heart function in PAH mouse models, meanwhile, it also reverses proliferation and cell cycle progression of pulmonary artery smooth muscle cells (PASMCs). To illustrate the mechanism of irisin exerts on PAH, Enolase 1 is identified as a key irisin-interacting protein. Irisin suppresses proliferation of PDGF-induced PASMCs by promoting ubiquitination status of Enolase 1 via E3 ligase of down regulated protein 4 in neural precursor cell development. Co-immunoprecipitation and molecular docking analyses verifies the interaction and binding sites between irisin and its interactive proteins. Overall, these findings suggest that, irisin is a novel protective factor downregulated in PAH. By ubiquitination, irisin promotes Enolase 1 degradation and suppresses cell proliferation and pulmonary vascular remodeling in PAH.

PMID:40560058 | DOI:10.1002/advs.202500096

J Cardiovasc Dev Dis. 2025 Jun 12;12(6):222. doi: 10.3390/jcdd12060222.

ABSTRACT

Background: Antegrade root cardioplegia remains the most popular strategy for myocardial protection during coronary artery bypass graft (CABG) performed with cardiopulmonary bypass (CPB) and aortic cross clamp. In patients with depressed left ventricular function, however, especially if associated with severe multiple coronary stenosis, increased pharmacological and/or mechanical support in the early post-CPB period is often required to support left ventricular recovery. In this study, we analyzed the results of a myocardial protection strategy that includes selective infusion of cardioplegia through each venous graft followed by warm reperfusion distal to each coronary anastomosis until complete removal of the aortic clamp (total antegrade cardioplegia infusion and warm reperfusion = TAWR) to improve early postoperative recovery in patients with depressed left ventricular function undergoing multi-vessel CABG. Methods: Out of 97 patients undergoing CABG using the TAWR strategy for myocardial protection, 32 patients presented with depressed left ventricle function (EF < 40%) and multi-vessel coronary diseases requiring ≥2 vein grafts and were enrolled as Group A. Combined primary outcomes and postoperative early and late left ventricle recovery (including spontaneous rhythm recovery, inotropic support and postoperative troponin release) were analyzed and compared with those of 32 matched patients operated on using standard antegrade root cardioplegia and limited warm reperfusion through LIMA graft (SAWR) enrolled as Group B. Results: Two patient died in hospital (in-hospital mortality 3.1%) with no statistical differences between the two groups. In Group A 27 patients (90%) had spontaneous recovery of idiopathic rhythm compared to 17 (53%) in group B (p = 0.001). Early inotropic support was required in nine patients (28%) of group A and seventeen patients (53%) of group B (p = 0.041). Furthermore, in eight patients (25%) of group A and seventeen (53%) of group B (p = 0.039) inotropic support was continued for >48 h. Conclusions: The TAWR strategy seems to significantly improve early postoperative cardiac recovery in patients with left ventricle depression undergoing multi-vessel CABG, when compared with SAWR strategy and could therefore be considered the strategy of choice in this subset of patients.

PMID:40558657 | PMC:PMC12193456 | DOI:10.3390/jcdd12060222

Cells. 2025 Jun 18;14(12):924. doi: 10.3390/cells14120924.

ABSTRACT

Muscle loss unresponsive to nutritional supplementation affects up to 80% of cancer patients and severely reduces survival and treatment response. Exercise may help preserve muscle mass and function, yet the translatability of preclinical methods remains questionable. This study aimed to assess how voluntary wheel running, a clinically relevant physical activity, protects skeletal and cardiac muscle against cancer-mediated dysfunction and identify underlying molecular mechanisms.

METHODS: BALB/c mice were assigned to sedentary nontumor-bearing (SED+NT), sedentary tumor-bearing (SED+T), wheel run nontumor-bearing (WR+NT), and wheel run tumor-bearing (WR+T). Tumor-bearing groups received 5 × 105 C26 cells; WR mice had wheel access for 4 weeks. Muscle function and tissue were analyzed for protective mechanisms.

RESULTS: SED+T mice exhibited significant fat and lean mass loss, indicating cachexia, which was prevented in WR+T mice. SED+T also showed 15% reduced grip strength and cardiac dysfunction, while WR+T preserved function. WR+T mice had lower expression of muscle wasting markers (Atrogin1, MuRF1, GDF15, GDF8/11). Physical activity also reduced tumor mass by 57% and volume by 37%.

CONCLUSION: Voluntary wheel running confers tumor-suppressive, myoprotective, and cardioprotective effects. These findings support physical activity as a non-pharmacological strategy to combat cancer-related muscle wasting and dysfunction.

PMID:40558549 | PMC:PMC12190267 | DOI:10.3390/cells14120924

J Cardiovasc Dev Dis. 2025 May 29;12(6):205. doi: 10.3390/jcdd12060205.

ABSTRACT

INTRODUCTION: Pediatric heart transplantation (HTX) remains the only therapeutic option for end-stage heart failure not amenable to conventional surgical or catheter interventions. We reviewed our pediatric HTX outcomes according to primary diagnosis.

PATIENTS AND METHODS: Sixty-two patients underwent HTX between 01/2007 and 12/2022. Patients were divided into congenital heart disease (CHD, n = 20) and cardiomyopathy (CMP, n = 42) groups. All potential variables relevant to patient recovery and long-term survival with endpoints of retransplantation or death were analyzed.

RESULTS: CHD patients underwent HTX after significantly more multiple major cardiac surgeries per patient (2.5 [0-5]) than CMP patients (0.5 [0-2], p < 0.01), without notable allosensitization. Post-HTX recovery was longer in CHD (mean mechanical ventilation 7 vs. 3 days, p = 0.001), likely due to longer surgical time (468 vs. 375 min, p = 0.037). There were no significant differences in the frequency of rejections between the two groups (4/20 vs. 9/42). Midterm survival was slightly better (85/70% p = NS) in CMP (median follow-up 44.5 [0-177] months).

CONCLUSION: Our study confirmed good short- and long-term outcomes of pediatric HTX in both CMP and CHD. The longer postoperative recovery in CHD did not lead to higher mortality. No higher pretransplant hypersensitization was observed, possibly explaining the lack of difference in the number and severity of rejections.

PMID:40558640 | PMC:PMC12194210 | DOI:10.3390/jcdd12060205