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Sci Rep. 2025 Jul 3;15(1):23690. doi: 10.1038/s41598-025-09461-6.

ABSTRACT

Due to advances in medical and surgical care, there are more adults than children living with congenital heart disease (CHD). Acute kidney injury (AKI) is a common complication following cardiac surgery in patients with CHD, with creatinine lacking sensitivity for early detection. Renal functional reserve (RFR), the kidney's capacity to increase filtration under stress, has emerged as a potential predictor of AKI. Our primary study objective was to evaluate whether preoperative RFR, using both creatinine clearance (CrCl) and cystatin C estimated glomerular filtration rate (eGFR) methods, predicts AKI following cardiopulmonary bypass in young adults with CHD. As a secondary objective, we compared RFR in CHD patients to that of healthy controls. This prospective cohort study included 30 young adults (ages 18-40) with acyanotic CHD and 8 healthy controls with normal baseline kidney function by serum creatinine. Preoperative RFR was measured using CrCl and cystatin C eGFR before and after a protein load. Postoperative AKI was diagnosed using the Kidney Disease Improving Global Outcomes criteria. Twelve (40%) CHD patients developed AKI, exhibiting significantly lower RFR when compared to those without AKI (median CrCl RFR: 9.6 vs. 35.0 mL/min/1.73m2; cystatin C eGFR RFR: 5.5 vs. 11.5 mL/min/1.73m2; P < 0.01). The ROC curve area for AKI prediction was 1.0 (CrCl RFR) and 0.88 (95% CI: 0.72-1.00, cystatin C eGFR RFR). CHD patients had lower RFR than controls (median CrCl: 25.5 vs. 56.4 mL/min/1.73m2, P < 0.01; median cystatin C eGFR: 9.0 vs. 13.5 mL/min/1.73m2, P = 0.03). In conclusion, preoperative RFR accurately predicts AKI in young adults with acyanotic CHD, providing a tool for the identification of high-risk patients and potentially improving perioperative care.

PMID:40604226 | DOI:10.1038/s41598-025-09461-6

Sci Rep. 2025 Jul 3;15(1):23690. doi: 10.1038/s41598-025-09461-6.

ABSTRACT

Due to advances in medical and surgical care, there are more adults than children living with congenital heart disease (CHD). Acute kidney injury (AKI) is a common complication following cardiac surgery in patients with CHD, with creatinine lacking sensitivity for early detection. Renal functional reserve (RFR), the kidney's capacity to increase filtration under stress, has emerged as a potential predictor of AKI. Our primary study objective was to evaluate whether preoperative RFR, using both creatinine clearance (CrCl) and cystatin C estimated glomerular filtration rate (eGFR) methods, predicts AKI following cardiopulmonary bypass in young adults with CHD. As a secondary objective, we compared RFR in CHD patients to that of healthy controls. This prospective cohort study included 30 young adults (ages 18-40) with acyanotic CHD and 8 healthy controls with normal baseline kidney function by serum creatinine. Preoperative RFR was measured using CrCl and cystatin C eGFR before and after a protein load. Postoperative AKI was diagnosed using the Kidney Disease Improving Global Outcomes criteria. Twelve (40%) CHD patients developed AKI, exhibiting significantly lower RFR when compared to those without AKI (median CrCl RFR: 9.6 vs. 35.0 mL/min/1.73m2; cystatin C eGFR RFR: 5.5 vs. 11.5 mL/min/1.73m2; P < 0.01). The ROC curve area for AKI prediction was 1.0 (CrCl RFR) and 0.88 (95% CI: 0.72-1.00, cystatin C eGFR RFR). CHD patients had lower RFR than controls (median CrCl: 25.5 vs. 56.4 mL/min/1.73m2, P < 0.01; median cystatin C eGFR: 9.0 vs. 13.5 mL/min/1.73m2, P = 0.03). In conclusion, preoperative RFR accurately predicts AKI in young adults with acyanotic CHD, providing a tool for the identification of high-risk patients and potentially improving perioperative care.

PMID:40604226 | DOI:10.1038/s41598-025-09461-6

Circ Heart Fail. 2025 Jul 3:e012716. doi: 10.1161/CIRCHEARTFAILURE.124.012716. Online ahead of print.

ABSTRACT

BACKGROUND: Assessment of medication changes in heart failure trials and registries is complex and may not capture the entirety of care. A comprehensive and standardized method is needed. We used different methods to assess the use of guideline-directed medical therapies (GDMT) and verified the association between GDMT intensity score with the STRONG-HF trial (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing of Heart Failure Therapies) clinical outcomes.

METHODS: We used data from the STRONG-HF trial to examine the baseline GDMT use for all randomized patients by applying the GDMT intensity score and evaluated its change over time. We also examined their basic adherence, indication-corrected adherence, and dose-corrected adherence, and the association with clinical outcomes up to 180 days.

RESULTS: At 90 days, triple therapy indication-corrected use increased from 4.5% to 36% in the usual care group, and from 5.2% to 93.5% in the high-intensity care group (P<0.001 between the 2 groups). Triple therapy dose-corrected use increased from 4.5% to 20.5% in the usual care group, and from 3.3% to 77.4% in the high-intensity care group (P<0.001). The GDMT intensity score at baseline was <6 in 358 (33%) patients, 6 to 7 in 329 (31%) patients, and >7 in 386 (36%) patients. At 90 days, 88.4% of patients in the high-intensity arm achieved a score >7 versus 14.3% in the usual care arm (P<0.0001). The GDMT intensity score was correlated with clinical outcomes at 180 days.

CONCLUSIONS: The GDMT intensity score provides a comprehensive description of medication use by means of standardized measurements and is linked to clinical outcomes. Future studies should consider utilizing this as a trial end point.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03412201.

PMID:40605744 | DOI:10.1161/CIRCHEARTFAILURE.124.012716

Circ J. 2025 Jul 1. doi: 10.1253/circj.CJ-25-0028. Online ahead of print.

ABSTRACT

BACKGROUND: The effect of the location of calcification in the left main coronary artery (LMCA) bifurcation on cardiovascular events remains unclear.

METHODS AND RESULTS: This retrospective study included 498 patients who underwent LMCA stenting at a single center between 2014 and 2018. Moderate or severe calcification was visually assessed by coronary angiography. The primary endpoint was 3-year target lesion failure (TLF), defined as cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. Most patients (n=314; 63.1%) had no calcification in the LMCA bifurcation. One-segment calcification was observed in 45 (9.0%) patients, primarily in the left anterior descending artery (LAD; n=43 [8.6%]). Two-segment calcification was observed in 81 (16.3%) patients, most commonly involving the LMCA and LAD (n=70; 14.1%). Three-segment calcification was observed in 58 (11.6%) patients. Overall, 58 (11.6%) patients developed TLF within 3 years. Multivariable Cox regression analysis revealed a significant association between calcification in the left circumflex artery (LCX) and 3-year TLF (adjusted hazard ratio [aHR] 4.46; 95% confidence interval [CI] 1.81-10.99; P=0.001). In contrast, there was no significant association between calcification at the LMCA (aHR 1.29; 95% CI 0.47-3.55; P=0.623) or LAD (aHR 0.49; 95% CI 0.17-1.45; P=0.199) and the primary endpoint.

CONCLUSIONS: Moderate or severe calcification in the LCX is significantly associated with 3-year TLF in patients who have undergone LMCA stenting.

PMID:40603065 | DOI:10.1253/circj.CJ-25-0028

J Gen Intern Med. 2025 Jul 2. doi: 10.1007/s11606-025-09701-5. Online ahead of print.

ABSTRACT

BACKGROUND: Transgender and gender diverse (trans) populations are at elevated risk for atherosclerotic cardiovascular disease (ASCVD).

OBJECTIVE: Measure the association of gender identity and gender-affirming hormone therapy (GAHT) with ASCVD outcomes.

DESIGN: Cohort study.

PARTICIPANTS: Over 1 million veterans receiving care in the Veterans Health Administration.

MAIN MEASURES: Gender identity was identified via a validated natural language processing (NLP) algorithm. Incident ASCVD (acute myocardial infarction, ischemic stroke, or revascularization after the baseline date) was identified via International Classification of Diseases diagnosis codes among veterans without prevalent ASCVD. We calculated sample statistics stratified by gender identity and used Cox proportional hazard regression to assess associations of gender identity and GAHT with incident ASCVD.

KEY RESULTS: Among 1,105,082 veterans, 42,149 were classified as trans (8013 transfeminine, 7127 transmasculine, and 27,009 uncategorized trans) while 918,843 were cisgender men and 144,090 were cisgender women. During a median follow-up of 9.39 years, 92,910 veterans had incident ASCVD (2806 among trans veterans). Adjusting for age, race, Hispanic ethnicity, and sexual orientation, trans veterans had 1.52 [1.45, 1.59] and 0.92 [0.89, 0.96] times the hazard of ASCVD compared to cisgender women and cisgender men, respectively. Compared to trans veterans not receiving GAHT, GAHT among trans veterans assigned female at birth was significantly associated a reduced hazard of ASCVD (0.89 [0.80, 0.98]); GAHT was not associated with ASCVD among trans veterans assigned male at birth (0.99 [0.89, 1.09]).

LIMITATIONS: With NLP, there is potential for selection bias as clinicians may preferentially document the gender identity for trans more than cisgender veterans.

CONCLUSIONS: This is one of the first studies to examine the association of both gender identity and GAHT with incident ASCVD in veterans. Future research must comprehensively evaluate ASCVD outcomes and the effects of gender-affirming care (including hormone therapy) in trans populations.

PMID:40601199 | DOI:10.1007/s11606-025-09701-5

Sci Rep. 2025 Jul 2;15(1):23660. doi: 10.1038/s41598-025-09105-9.

ABSTRACT

This study aims to investigate the protective effects of curcumin (CUR) in high glucose (HG)-induced oxidative stress and apoptosis of primary cardiomyocytes by activating the Notch1 signaling pathway. CUR is a natural polyphenol isolated from turmeric rhizomes and is known for its antioxidant, anti-apoptotic, and anti-inflammatory effects, particularly relevant in diabetes.Therefore, we used neonatal rat cardiomyocytes exposed to HG conditions, followed by treatment with CUR and DAPT, respectively. We detected and assessed myocardial cells viability and antioxidant enzyme activity by CCK-8 reagent and antioxidant enzyme kit. Apoptosis was detected by flow cytometry. The production of reactive oxygen species was detected by fluorescence labeling, and the expression of related genes and proteins was detected by qRT-PCR and Western blot. HG-induced primary rat cardiomyocytes not only increased apoptosis and ROS production, but also decreased the activity of antioxidant enzymes and the expression of Notch1 and Hes1 proteins. After pre-treatment by CUR, surprisingly, we found that CUR markedly improved viability of HG-treated cardiomyocytes. The results showed that CUR could inhibit the apoptosis of rat cardiomyocytes, inhibit the production of intracellular ROS, and increase the activity of antioxidant enzymes. Further, we found that CUR can upregulate the expression of Notch1 and Hes1 proteins and related genes, suggesting that the protective effect of CUR on HG-induced damage involves the Notch1/Hes1 signaling. These results suggest that CUR protects cardiomyocytes from HG-induced oxidative stress by activating Notch1 and its downstream target genes.

PMID:40603691 | DOI:10.1038/s41598-025-09105-9

J Cardiothorac Vasc Anesth. 2025 Jun 8:S1053-0770(25)00473-2. doi: 10.1053/j.jvca.2025.06.015. Online ahead of print.

ABSTRACT

This second part of a two-part review on the cardiovascular pharmacology of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) describes the mechanisms that have been proposed to explain how these drugs improve outcomes in heart failure and myocardial infarction and discusses their adverse effects and perioperative implications for patients with or without diabetes undergoing major surgery. The mechanism(s) by which SGLT2i exert beneficial cardiovascular actions are incompletely understood at present, but they are most likely multifactorial in origin, as no single factor has been proven definitive when considered alone. SGLT2i increase the risk of genital mycotic infections and diabetic ketoacidosis (DKA) in patients with diabetes, but the drugs do not cause severe hypoglycemia requiring intervention, urinary tract infection, hypovolemia, or acute kidney injury, among other postulated adverse outcomes. Perioperative euglycemic DKA (euDKA) is rare, but vigilance for its occurrence is required when an anion gap metabolic acidosis develops despite normal or only modestly elevated glucose concentration. Current guidelines recommend withholding SGLT2i for at least 48 hours to minimize the risk of DKA before elective major surgery in patients with but not without diabetes. The guidelines further emphasize the need to maintain a high index of suspicion for DKA and euDKA when SGLT2i therapy cannot be stopped because of urgent or emergent surgery so that appropriate treatment can be promptly initiated to prevent morbidity and mortality.

PMID:40603214 | DOI:10.1053/j.jvca.2025.06.015

J Mol Cell Cardiol. 2025 Jun 30:S0022-2828(25)00109-9. doi: 10.1016/j.yjmcc.2025.06.011. Online ahead of print.

ABSTRACT

The aging-associated cardiac remodeling (AACR) is characterized by myocardial hypertrophy, fibrosis and cardiac dysfunction, which could be further aggravated by angiotensin II (Ang II) and pressure-overload in aged people. In this study, we aimed to investigate the roles and mechanisms of intermedin1-53 (IMD1-53), an endogenous peptide, in AACR in aged mice (18 months) with subcutaneous Ang II infusion (1000 ng/kg/min) for 2 weeks via osmotic pump or transverse abdominal aorta constriction (AAC) surgery for 4 weeks. In aged mice undergoing Ang II infusion or AAC surgery, the results showed that the mRNA and protein levels of IMD1-53 were significantly reduced, but the protein levels of its receptor complex components were increased; blood pressure (BP), myocardial hypertrophy, fibrosis, and cardiac dysfunction were notably aggravated; mitochondrial Sirtuin 3 (SIRT3) protein level, superoxide dismutase 2 (SOD2) activity and ATP production were remarkably decreased, but acetylated SOD2 (acSOD2) protein level was markedly increased when compared with the old mice. The above alterations could be effectively alleviated by the subcutaneous IMD1-53 administration (5 ng/kg/min) for 2 or 4 weeks. In Ang II-stimulated cardiomyocytes, IMD1-53 treatment improved Ang II-induced mitochondrial dysfunction and oxidative distress, up-regulated SIRT3 protein expression, and reduced acSOD2 protein level, which were notably weakened by SIRT3 knockdown. Moreover, SIRT3 deletion attenuated the protective effects of IMD1-53 on myocardial hypertrophy, fibrosis, and cardiac dysfunction in aged mice undergoing Ang II infusion. In addition, the effect of IMD1-53 on up-regulating SIRT3 expression was effectively inhibited by the antagonism of IMD1-53 receptor or blocking PI3K/Akt, cAMP/PKA and AMPK signaling pathways in vitro. Taken together, IMD1-53 alleviated AACR and cardiac dysfunction aggravated by Ang II or pressure-overload involving the improvement of mitochondrial oxidative distress through SIRT3-medaiated SOD2 deacetylation.

PMID:40602647 | DOI:10.1016/j.yjmcc.2025.06.011

Fitoterapia. 2025 Jun 30:106721. doi: 10.1016/j.fitote.2025.106721. Online ahead of print.

ABSTRACT

Hypoxic myocardial injury is the core mechanism of many cardiovascular diseases and poses a serious threat to global public health. Its pathogenesis involves energy metabolism disorder, oxidative stress, inflammatory response, apoptosis regulation imbalance, and other links, resulting in myocardial dysfunction and damage. In recent years, a large number of studies have confirmed that the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling network can regulate hypoxic myocardial injury by mediating HMGB1, MyD88, Caspase-3, HIF-1α, TNF-α, NLRP3, HSP70, etc. Traditional Chinese Medicine (TCM) and its active components have obvious advantages in the treatment of complex diseases such as hypoxic myocardial injury, and inhibiting the key target of TLR4/NF-κB signaling network is one of the mechanisms of myocardial protection. However, there are few systematic reviews and summaries in this field. Based on this, this review summarizes the regulatory mechanism of TLR4/NF-κB signaling pathway involved in hypoxic myocardial injury and the intervention effect of TCM in recent years, to provide a theoretical basis for basic research and new drug development of hypoxic myocardial injury.

PMID:40602631 | DOI:10.1016/j.fitote.2025.106721

Phytomedicine. 2025 Jun 20;145:157006. doi: 10.1016/j.phymed.2025.157006. Online ahead of print.

ABSTRACT

BACKGROUND: Septic cardiomyopathy (SCM) is associated with sepsis and is often accompanied by progressive arrhythmia. Naringenin (Nar) is a natural dihydroflavonoid compound that plays a protective role in various cardiovascular diseases. Calcium/calmodulin-dependent kinase II (CaMKII) is a key therapeutic target in cardiac arrhythmias.

PURPOSE: This study investigated the effect of naringenin on arrhythmia and cardiac electrophysiology in SCM and explored the mechanism involved.

METHODS: Lipopolysaccharide was used to establish SCM in a mouse model and in an H9c2 cell line. The protective role of naringenin in SCM was investigated by pretreatment with naringenin, amiodarone, and a CaMKII inhibitor (KN-93). Cardiac function, susceptibility to arrhythmia, and electrophysiological changes were assessed in the mice using echocardiography, electrocardiography, and optical mapping techniques. Network pharmacology approaches, molecular docking, and molecular dynamics simulations were used to screen for pivotal targets. The mechanism(s) underlying the protective impact of naringenin on SCM were examined in vivo, ex vivo, and in vitro.

RESULTS: Naringenin protected against SCM by exerting anti-inflammatory effects, alleviating myocardial injury, improving cardiac dysfunction, reducing the susceptibility to arrhythmia, and stabilizing electrophysiology. Network pharmacology, molecular docking, and molecular dynamics simulations indicated that the key target protein of naringenin may be Bcl-2. Further studies confirmed that naringenin attenuated apoptosis, improved mitochondrial dysfunction, and downregulated the CaMKⅡ/Drp1/Bcl-2 pathway in SCM.

CONCLUSIONS: Naringenin attenuates the phosphorylation of Drp1 by inhibiting phosphorylation of CaMKⅡ, thereby ameliorating mitochondrial dysfunction, suppressing apoptosis, modulating myocardial electrophysiology, and ultimately reducing susceptibility to arrhythmia while improving cardiac function in SCM.

PMID:40602293 | DOI:10.1016/j.phymed.2025.157006

Phytomedicine. 2025 Jun 18;145:157011. doi: 10.1016/j.phymed.2025.157011. Online ahead of print.

ABSTRACT

BACKGROUND: Hydroxysafflor yellow A (HSYA), the primary active constituent of Safflower, a traditional Chinese medicine, has demonstrated promising therapeutic potential in the treatment of cardiovascular and cerebrovascular injuries. However, the impact of HSYA on stroke-induced cardiac syndrome and the underlying mechanisms remain to be elucidated.

METHODS: Laser super-resolution microscopy and transmission electron microscopy were employed to examine cerebral ischemic injury. Echocardiography and immunofluorescence techniques were utilized to assess cardiac function and inflammatory damage. Western blot analysis was conducted to measure the expression levels of apoptosis-related proteins in heart tissue.

RESULTS: HE revealed that SHS induced inflammatory infiltration in the myocardium. Echocardiographic findings indicated that SHS impaired cardiac function. ELISA results demonstrated that SHS led to elevated levels of norepinephrine and epinephrine. Transmission electron microscopy (TEM) observations confirmed that SHS resulted in mitochondrial damage within cardiac cells. Immunofluorescence analysis further showed that SHS facilitated the recruitment of cardiac macrophages, upregulated the expression of ZBP1 and NLRP3, and increased the production of inflammatory cytokines and inflammasomes. Co-immunoprecipitation experiments demonstrated that ZBP1 interacts with NLRP3. Inhibiting sympathetic overactivation exerts a protective effect on the heart. Furthermore, HSYA not only reversed the aforementioned conditions but also exerted protective effects on both cardiac and cerebral tissues. Immunofluorescence analysis revealed that HSYA inhibited the formation of the ZBP1 and NLRP3 complexes, as well as the inflammasome complex. Molecular docking studies indicated that HSYA and ZBP1 share the LYS-166 binding site, and protein docking results demonstrated that ZBP1 and NLRP3 also share this binding site. Mutations at this site diminished the protective efficacy of HSYA against SHS.

CONCLUSIONS: HSYA mitigates macrophage recruitment through the inhibition of the ZBP1-NLRP3 signaling pathway, thereby improving sympathetic nerve function, suppressing panoptosis, and alleviating SHS injury by competitively binding to the LYS-166 site of ZBP1 with NLRP3.

PMID:40602292 | DOI:10.1016/j.phymed.2025.157011

JACC Heart Fail. 2025 Jul 1;13(8):102479. doi: 10.1016/j.jchf.2025.02.025. Online ahead of print.

ABSTRACT

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) block the activation of mineralocorticoid receptors by aldosterone, thereby mitigating cardiovascular risks. However, data on whether impact of aldosterone on outcomes differs with MRA use remain limited.

OBJECTIVES: The study aims to explore the associations between baseline aldosterone, its changes and outcomes, and their interaction with eplerenone.

METHODS: In a subset of the EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) trial, associations between baseline serum aldosterone concentrations, their changes from baseline to month 1, and outcomes were separately assessed in the eplerenone and placebo groups. The primary outcome was a composite of cardiovascular death or heart failure (HF) hospitalization.

RESULTS: Among 453 patients (mean age: 62 ± 11 years; 75% male), baseline median serum aldosterone was 5.6 ng/dL (Q1-Q3: 3.1-9.2 ng/dL). Higher baseline serum aldosterone was associated with primary outcome in the placebo group (HR per 1 ng/dL: 1.04 ng/dL [95% CI: 1.02-1.07 ng/dL]; P = 0.002), but not in the eplerenone group (HR per 1 ng/dL: 0.99 ng/dL [95% CI: 0.93-1.05 ng/dL]; P = 0.64; P for interaction = 0.048), and these associations persisted after covariate adjustment (ie, prior HF history and renal function). At month 1, eplerenone increased serum aldosterone more than placebo (P < 0.001). High serum aldosterone changes (≥ median value) were associated with increased risk of primary outcome in the placebo group but not in the eplerenone group (HR: 3.48 [95% CI: 1.35-8.99]; P = 0.01 in placebo; HR: 0.81 [95% CI: 0.36-1.82]; P = 0.60 in eplerenone; P for interaction = 0.046), and these associations persisted after covariate adjustment.

CONCLUSIONS: In patients with left ventricular systolic dysfunction and/or HF after myocardial infarction, higher baseline or rising aldosterone levels were associated with increased risk of HF events. However, eplerenone mitigated aldosterone-associated risks.

PMID:40602178 | DOI:10.1016/j.jchf.2025.02.025

Hum Exp Toxicol. 2025 Jan-Dec;44:9603271251354890. doi: 10.1177/09603271251354890. Epub 2025 Jul 2.

ABSTRACT

PurposeThis study investigated the mechanism by which Rosmarinic acid (RA) may alleviate doxorubicin (DOX)- induced cardiomyocyte apoptosis.MethodsThe target genes of RA, DOX-related differentially expressed genes, and GEO database related genes were retrieved by bioinformatics analyses. The results of these analyses were further intersected to identify candidate genes. The protein-protein interaction network was constructed to develop the pharmacophore model. The molecular docking was simulated to determine the core target B-cell lymphoma 2-like 1 (BCL2L1) for subsequent molecular mechanism investigation in vitro. The effects of DOX and RA on the apoptosis of H9c2 cells were assessed using the CCK8 assay. The present study investigated the effect of RA on DOX-induced oxidative stress in cardiomyocytes. This investigation was conducted using an ELISA test and a DCFH-DA probe. The JC-1 probe was utilized to assess the effect of RA on DOX-induced cardiomyocyte mitochondrial membrane permeability. A Western blot assay was conducted to ascertain the activation of multiple signaling molecules, including those belonging to the BCL-2 and caspase-3 families, within the apoptosis pathway.ResultsA total of 17 differentially expressed genes (DEGs) were screened, and five genes were selected as hub DEGs. A subsequent KEGG enrichment analysis revealed that these DEGs were significantly enriched in various biological processes and pathways, including the MAPK signaling pathway, autophagy, apoptosis, and the TNF signaling pathway. The pharmacophore model and molecular docking of five candidate targets with RA were successfully established. It is noteworthy that DOX treatment led to a suppression of SOD and GSH levels, an exacerbation of oxidative stress, and a promotion of cardiomyocyte apoptosis. Furthermore, it has been demonstrated to suppress mitochondrial membrane permeability. Subsequent RT-qPCR analysis of the hub genes revealed that only BCL2L1 exhibited significant alterations. Treatment with DOX altered the expression levels of apoptosis-associated proteins, BCL-2 family members, and caspase-3 family members. However, the administration of RA mitigated the deleterious effects of DOX on cardiomyocytes.ConclusionsThe protective effects of RA may against myocardial cell apoptosis are likely mediated through its activation of BCL2L1 and inhibition of caspase cascade protein expression in myocardial cells.

PMID:40600628 | DOI:10.1177/09603271251354890

BMC Res Notes. 2025 Jul 1;18(1):263. doi: 10.1186/s13104-025-07308-x.

ABSTRACT

OBJECTIVE: This study aimed to explore the protective mechanism of Phellinus linteus polysaccharides (Phps) against hypoxia/reoxygenation (H/R)-induced injury in H9c2 cardiomyocytes, focusing on oxidative stress, apoptosis, and PI3K-AKT pathway regulation.

RESULTS: H9c2 cardiomyocytes were divided into control, H/R model, and Phps-treated groups (low/medium/high doses). The H/R model (established by exposing cells to hypoxia for 10 h followed by 4 h of reoxygenation.) induced significant injury: cell viability decreased, SOD activity reduced by 45%, and Bcl-2 expression declined at both mRNA and protein levels, while LDH activity increased by 66%, MDA content surged by 99%, and Bax expression (mRNA/protein) and p-PI3K and p-AKT levels were upregulated, with statistical significance (P < 0.05 vs. control). Compared to the H/R model group, the Phps treatment (low, medium, high) groups showed a significant increase in H9c2 cardiomyocytes viability, SOD activity, and mRNA and protein expression levels of Bcl-2. The LDH activity, MDA content, mRNA levels of Bax, and protein expression levels of Bax, p-PI3K and p-AKT significantly decreased, with statistical significance (P < 0.05). These results suggest that Phps may improve H/R induced damage in H9c2 cardiomyocytes by downregulating the ratio of Bax/Bcl-2 through the PI3K-AKT pathway.

PMID:40598329 | PMC:PMC12220461 | DOI:10.1186/s13104-025-07308-x

Ann Thorac Cardiovasc Surg. 2025;31(1). doi: 10.5761/atcs.oa.25-00075.

ABSTRACT

PURPOSE: Pericardial effusion (PE), tamponade, and atrial fibrillation are challenging complications after cardiac surgeries. This prospective randomized study was conducted to evaluate the impact of posterior pericardiotomy (PP) in the prevention of PE and cardiac tamponed after adult cardiac surgery.

METHODS: This single-center, prospective, randomized controlled trial included 330 patients undergoing open-heart surgery. They were randomly assigned to either a PP group or a control group.

RESULTS: Of 703 screened patients, 330 were enrolled from January 2022 to June 2024 (mean age: 50.2 ± 14.7 years, 64.2% males). Compared to controls, the PP group had significantly lower early and late PE (19.4% vs. 44.8%, and 4.2% vs. 17%, respectively), tamponade (2.4% vs. 11.5%), and postoperative atrial fibrillation (10.3% vs. 19.4%). PP also significantly reduced the need for surgical re-exploration, duration of mechanical ventilation, and both intensive care unit and overall hospital stays (all P <0.05). Adjusted multivariate analysis confirmed the benefits of PP after correcting for baseline imbalances in left ventricular ejection fraction and operative time. No adverse events directly attributable to PP were noted.

CONCLUSIONS: PP is a simple, safe, and effective technique for reducing postoperative PE, and cardiac tamponade after cardiac surgery.

PMID:40603058 | DOI:10.5761/atcs.oa.25-00075

Curr Probl Cardiol. 2025 Jun 30:103125. doi: 10.1016/j.cpcardiol.2025.103125. Online ahead of print.

ABSTRACT

Cardiac amyloidosis (CA) is a once underdiagnosed and often fatal condition that has evolved into a disease with expanding diagnostic and therapeutic possibilities. It is characterized by the extracellular deposition of misfolded amyloid proteins within the myocardium, leading to structural and functional impairment. Advances in understanding the pathophysiology encompassing the amyloid protein misfolding, aggregation and deposition in cardiac tissue as well as the role of genetic factors have been pivotal in driving progress in diagnosis and management. The deposition of amyloid proteins can lead to significant cardiac manifestations, including constrictive cardiomyopathy, heart failure (both preserved and reduced ejection fraction), and arrhythmias particularly atrial fibrillation, contributing to substantial morbidity and mortality. Diagnostic innovations, such as advanced imaging and novel biomarkers, have enabled early detection and precise subtype differentiation, underscoring the need for targeted therapies. Over the past decade, therapeutic advancements have introduced transformative medications that gained FDA approval for the management of transthyretin amyloidosis (ATTR) including transthyretin stabilizers and silencers. Promising strategies like gene editing, antisense oligonucleotides and monoclonal antibodies are currently under investigation. However, managing cardiac manifestations remains challenging, particularly in optimizing euvolemia and rate control in heart failure and atrial fibrillation with limitations in traditional medications. This review explores the evolving landscape of CA, from pathophysiologic insights to innovative therapies, and provides a comprehensive approach to the management of cardiac manifestations to address ongoing challenges this condition.

PMID:40602734 | DOI:10.1016/j.cpcardiol.2025.103125

Int Immunopharmacol. 2025 Jul 1;162:115155. doi: 10.1016/j.intimp.2025.115155. Online ahead of print.

ABSTRACT

BACKGROUND: Immune rejection remains a leading cause of graft loss following organ transplantation, with CD4+ T cells playing a central role in this process. The PI3K/AKT/mTOR signaling pathway is essential for the activation, proliferation, and metabolic reprogramming of CD4+ T cells, making it an attractive therapeutic target. However, the role of Idelalisib (ID), a selective PI3Kδ inhibitor, in transplant immunity remains underexplored.

METHODS: Purified CD4+ T cells from the spleens of C57BL/6 mice were cultured with ID. Activation, proliferation, differentiation and survival were evaluated. A fully mismatched skin and heart transplantation model was used to assess ID's effects on rejection. Histopathology analysis and transcriptomic sequencing were performed.

RESULTS: ID significantly suppressed CD4+ T cell activation, proliferation, and Th1 differentiation, while enhancing cell survival-contrasting with the pro-apoptotic effects observed with the mTOR inhibitor rapamycin (Rapa). In the skin and heart transplantation models, ID reduced acute rejection, extended graft survival, and decreased the proliferation of CD4+ T cells and B cells. Transcriptomic analysis revealed downregulation of genes involved in T cells activation and differentiation (e.g., Zap70, Stat4), as well as markers of glycolysis (e.g., Gapdh, Pfkm). Functional assays confirmed reduced glucose uptake and lactate production in ID-treated cells.

CONCLUSIONS: ID uniquely modulates T cell responses through PI3Kδ inhibition, providing a distinct immunosuppressive mechanism from that of mTOR inhibitors. These findings highlight the therapeutic potential of ID in preventing transplant rejection and reveal a critical link between PI3K signaling and CD4+ T cell metabolism.

PMID:40602262 | DOI:10.1016/j.intimp.2025.115155

Braz J Cardiovasc Surg. 2025 Jul 2;40(5):e20240310. doi: 10.21470/1678-9741-2024-0310.

NO ABSTRACT

PMID:40601830 | DOI:10.21470/1678-9741-2024-0310

Sci Adv. 2025 Jul 4;11(27):eadv4854. doi: 10.1126/sciadv.adv4854. Epub 2025 Jul 2.

ABSTRACT

Cardiovascular diseases are a leading cause of mortality, with limited possibilities for transplantation due to a critical shortage of donor hearts. Replacing the heart with total artificial hearts (TAHs) remains challenging, due to size constraints and energy requirements, among others. To address this, we introduce the LIMO heart, a compact TAH concept based on an efficient soft fluidic transmission system. By reducing actuator volume and enhancing energy transfer, LIMO enables a more compact and efficient design. We developed a soft ventricle prototype using thin-walled pouch actuators that achieve transmission ratios above one via circumferential shrinkage. A fast, cost-effective prototyping method accelerated testing. Experimental results showed high energy transfer efficiency (82 to 91%), and in vitro tests demonstrated promising cardiac outputs of 5.9 liters per minute against aortic pressure and 7.6 liters per minute against pulmonary pressure. These findings represent a step toward a more broadly applicable biventricular soft robotic TAH for treating end-stage heart failure.

PMID:40601721 | DOI:10.1126/sciadv.adv4854

PLoS One. 2025 Jul 2;20(7):e0325668. doi: 10.1371/journal.pone.0325668. eCollection 2025.

ABSTRACT

INTRODUCTION: Heart failure (HF) is among the most prevalent health issues worldwide and is associated with high mortality. Adequate decongestion remain the main clinical challenge in HF management. Sodium glucose cotransporter-2 inhibitors (SGLT-2i) have been recently introduced as a new treatment option in patients with HF irrespective of left ventricular ejection fraction. Although the favorable effects of SGLT-2i are profoundly evident, the underlying mechanisms are not yet well understood. The aim of this study is to provide novel insights into the effects of dapagliflozin, a SGLT-2i with proven cardiovascular benefit, on blood volume profile and vascular function in HF patients who had a recent event of acute decompensated heart failure (ADHF).

METHODS: Eighty adult patients with diagnosis of de novo or chronic HF (NYHA class II-IV), clinically stabilized after an ADHF event and with preserved renal function, who were not on treatment with SGLT-2i, are aimed to be included. The patients are randomized with 1:1 allocation to either dapagliflozin 10 mg p.o. once daily or placebo in addition to guideline-directed medical therapy. The primary outcome is the mean change in plasma volume status (PVS) in the dapagliflozin group compared to placebo. PVS is assessed via optimized carbon monoxide rebreathing technique, a reliable and safe method to measure total hemoglobin mass and to estimate blood volume profile, i.e., blood volume, plasma volume and red blood cell volume. Secondary outcomes include differences between the two study groups regarding blood volume profile, micro- and macro-vascular function assessed by retinal vessel analysis and flow-mediated vasodilation, respectively, changes in body water distribution, quality of life, exercise capacity, echocardiographic and laboratory parameters.

ETHICS AND DISSEMINATION: The study has been approved by the Cantonal Ethics Committee Zurich (BASEC-Nr.:2020-01920, Swissmedic-Nr.:2020DR4175) and has been registered at www.ClinicalTrials.gov‌ (NCT04869124). The results will be published in a peer-reviewed medical journal.

PMID:40601599 | DOI:10.1371/journal.pone.0325668