JACC Case Rep. 2025 Jun 11;30(14):103684. doi: 10.1016/j.jaccas.2025.103684.
ABSTRACT
BACKGROUND: Dynamic coronary obstruction is a rare and potentially lethal condition, which may cause an acute coronary syndrome (ACS).
CASE SUMMARY: A young patient with metastatic rhabdomyosarcoma was transferred to our center's cardiac intensive care unit with a ventricular tachycardia (VT) storm. A cardiac mass was demonstrated on transthoracic echocardiography and computed tomography. Coronary angiography was performed owing to suspected compression of the coronary arteries. Dynamic obstruction in the left anterior descending artery (LAD) was demonstrated with the use of angiography and intravascular ultrasound. After successful ostial to mid-LAD stenting, there was no recurrence of VT episodes.
DISCUSSION: VT storm is a lethal condition that requires rapid diagnosis and treatment. Rarely, it can be caused by dynamic coronary obstruction.
PMID:40514127 | DOI:10.1016/j.jaccas.2025.103684
Curr Cardiol Rev. 2025 Jun 10. doi: 10.2174/011573403X357542250526072430. Online ahead of print.
ABSTRACT
INTRODUCTION: The PCSK9 enzyme is present mainly in the liver and is responsible for the degradation of LDL-C receptors. Currently, there are some drugs that inhibit this enzyme, such as alirocumab and evolocumab. Consequently, these drugs reduce serum LDL-C levels. Therefore, a systematic review and a meta-analysis were carried out in order to compare alirocumab against evolocumab in reducing cardiovascular outcomes.
METHODS: This systematic review was carried out in accordance with PRISMA and was registered in PROSPERO (CRD42024573217). The following databases were searched on July, 9, 2024: Pubmed, Web of Science and Scopus. Randomized clinical trials with a control group were included and meta-analyses were performed to assess relative risk (RR). The random effects model was used in heterogeneous samples. The articles were distributed into 2 subgroups: use of alirocumab and evolocumab.
RESULTS: Initially, 2,213 articles were found, of which 6 were included. In total, 62,119 patients participated. The RR values were significant for alirocumab in the following outcomes: myocardial infarction (MI) 0.85 (95% CI 0.77-0.93), stroke 0.75 (95% CI 0.60-0.94) and hospitalization for unstable angina 0.58 (95% CI 0.39-0.86), while for evolocumab they were significant for MI 0.75 (95% CI 0.68-0.83) and coronary revascularization 0.81 (95 CI % 0.75-0.88). There was a statistically significant difference between the drugs for hospitalization for unstable angina (p=0.02).
DISCUSSION: This study highlights the benefits of PCSK9 inhibitors, especially alirocumab, in reducing major cardiovascular events. Alirocumab significantly lowered hospitalizations for unstable angina, with a 42% reduction, and showed favorable outcomes in reducing myocardial infarction, coronary revascularization, and stroke. These reductions are clinically meaningful, as they lower morbidity, improve patient quality of life, and reduce healthcare costs. Both alirocumab and evolocumab are effective and safe, offering important therapeutic options for high-risk cardiovascular patients.
CONCLUSION: The use of alirocumab is preferable if the focus is to avoid hospitalizations for unstable angina or stroke, while evolocumab may be an option if one wants to avoid coronary revascularization. Both drugs are effective in reducing cardiovascular outcomes, but alirocumab was superior to evolocumab.
PMID:40511660 | DOI:10.2174/011573403X357542250526072430
Int J Cardiol Heart Vasc. 2025 May 27;59:101708. doi: 10.1016/j.ijcha.2025.101708. eCollection 2025 Aug.
ABSTRACT
BACKGROUND: Nicorandil is used to induce hyperemia when measuring fractional flow reserve (FFR). However, it is unknown whether the clinical outcome of patients assessed using nicorandil is similar to that of patients assessed using adenosine triphosphatase (ATP). We aimed to compare the clinical outcomes of nicorandil and ATP in the PCI and deferred groups.
METHODS: This retrospective study examined 492 patients with chronic coronary syndrome who underwent FFR assessment between February 2016 and December 2021. The patients received either nicorandil or ATP to induce hyperemia. The primary endpoints were all-cause death, myocardial infarction, and urgent revascularization. These clinical outcomes were followed up for three years and compared between the groups.
RESULTS: In the PCI group (161 patients), primary endpoint events occurred in 9 % of the nicorandil group and 11 % of the ATP group (Adjusted HR 1.10, 95 % CI 0.35-3.40, P = 0.87). In the deferred group (331 patients), primary events occurred in 7 % of the patients in both groups (Adjusted HR 1.39, 95 % CI 0.55-3.49, P = 0.49). Kaplan-Meier curves showed no significant differences in event rates between nicorandil and ATP in either group.
CONCLUSIONS: In the evaluation of FFR, nicorandil is a safe and simple alternative that shows similar clinical outcomes to ATP.
PMID:40510821 | PMC:PMC12159487 | DOI:10.1016/j.ijcha.2025.101708
Eur Stroke J. 2025 Jun 12:23969873251343828. doi: 10.1177/23969873251343828. Online ahead of print.
ABSTRACT
INTRODUCTION: We examined the prevalence and the characteristics of vessel wall (VW) lesions in young stroke patients and their relation to recurrent vascular events. We hypothesize that having VW lesions is associated with an increased risk on recurrent vascular events.
PATIENTS AND METHODS: Single-center prospective study of participants aged 18-50 years, with a transient ischemic attack (TIA) or ischemic stroke, who underwent high-resolution 3T magnetic resonance imaging (HR-MRI) with VW imaging. We included 10 controls with symptoms diagnosed as stroke mimics. The HR-MRI scans were reviewed by two neuroradiologists blinded for clinical information. Follow-up was conducted via telephone interviews. Recurrent vascular events were defined as TIA, cerebral stroke, myocardial infarctions, revascularization procedures, or vascular death.
RESULTS: We included 158 participants (median age: 41.5 years, IQR 33.0-46.4); 75 (47.5%) of whom were women. Of these, 44 (27.8%) participants had 81 VW lesions, primarily characterized by VW enhancement (74.1%). 86.4% of VW lesions were located in the corresponding ischemic territory, and 48.6% showed no MRA abnormalities. Almost half of the VW lesions were found in the rare causes subgroup, while 13.6% of the "cryptogenic" subgroup showed VW enhancement. VW lesions were not significantly associated with an increased risk of recurrent vascular events (HR 2.2, 95% CI: 0.7-6.6).
CONCLUSION: One in four young stroke patients have VW lesions, which were not related to an increased risk of recurrent vascular events. VW lesions were seen across all TOAST categories and were not specific to one stroke cause. Further research is needed to investigate the diagnostic and prognostic value of VW lesions in young stroke patients.
PMID:40509544 | PMC:PMC12165956 | DOI:10.1177/23969873251343828
J Clin Med. 2025 Jun 4;14(11):3969. doi: 10.3390/jcm14113969.
ABSTRACT
Background/Objectives: Previous research has established that beta-blockers significantly reduce all-cause mortality, cardiovascular mortality, and recurrent acute myocardial infarction (AMI) in patients with left ventricular dysfunction following AMI. However, their efficacy in patients with preserved left ventricular ejection fraction (LVEF) who undergo timely reperfusion and revascularization while receiving evidence-based medical management remains inconclusive. To address this uncertainty, we conducted a systematic review and meta-analysis to synthesize the available evidence on the impact of beta-blocker therapy in patients with AMI and preserved LVEF. Methods: A comprehensive literature search was conducted across PubMed, the Web of Science, and Scopus from their inception until November 2024. The search strategy incorporated three primary keywords and their corresponding Medical Subject Headings (MeSH) terms: "preserved", "myocardial infarction", and "beta-blocker". Data analysis was performed using Review Manager 5.4 software. A random-effects model was applied to account for the study's heterogeneity, while a fixed-effects model was utilized for homogeneous outcomes. Pooled odds ratios (ORs) and hazard ratios (HRs) were calculated for dichotomous outcomes, with a 95% confidence interval (CI) and a significance threshold of p < 0.05. Results: Beta-blocker therapy was significantly associated with a reduction in all-cause mortality compared to non-use, with an OR of 0.73 (95% CI: 0.61-0.88, p = 0.001) and an HR of 0.78 (95% CI: 0.67-0.91, p = 0.002). Similarly, beta-blocker administration was linked to a lower risk of cardiovascular mortality, demonstrating an OR of 0.76 (95% CI: 0.68-0.84, p < 0.00001) and an HR of 0.76 (95% CI: 0.59-0.99, p = 0.04). Furthermore, beta-blocker use was significantly correlated with a decreased risk of major adverse cardiovascular events (MACEs) compared to non-use, with an OR of 0.84 (95% CI: 0.75-0.95, p = 0.004) and an HR of 0.84 (95% CI: 0.71-0.99, p = 0.04). Conclusions: The current meta-analysis suggests a potential beneficial association between beta-blocker use and outcomes in patients with AMI and preserved LVEF, including lower rates of all-cause mortality, cardiovascular mortality, and MACEs; however, these findings should be interpreted with caution due to the observational nature of most included studies. Therefore, further randomized controlled trials (RCTs) are needed to confirm these findings, particularly in distinguishing outcomes among patients with and without heart failure.
PMID:40507730 | PMC:PMC12156146 | DOI:10.3390/jcm14113969
J Clin Med. 2025 May 27;14(11):3753. doi: 10.3390/jcm14113753.
ABSTRACT
Background/Objectives: In recent decades, shifting demographics and advancements in treating cardiovascular disease have altered the types of patients receiving coronary angiography (CA). However, data investigating the impact of kidney dysfunction stratified by the indication for CA are limited. Methods: Consecutive patients who underwent invasive CA at one institution between 2016 and 2022 were included in this study. Firstly, the prevalence and extent of coronary artery disease (CAD) in patients with different levels of kidney function was assessed. Secondly, the study examined how impaired kidney function affected long-term outcomes-specifically the risk of rehospitalization for heart failure (HF), acute myocardial infarction (AMI), or the need for coronary revascularization-at 36 months of follow-up. Results: A total of 7624 patients undergoing CA were included with a median estimated glomerular filtration rate (eGFR) of 68.9 mL/min/1.73 m2 (IQR: 50.8-84.3). In total, 63.7% of patients had an eGFR ≥ 60 mL/min/1.73 m2, 29.0% an eGFR of 30-<60 mL/min/1.73 m2, and 7.3% an eGFR of <30 mL/min/1.73 m2. Compared to patients with an eGFR ≥ 60 mL/min/1.73 m2, those with an eGFR 30-<60 mL/min/1.73 m2 and eGFR < 30 mL/min/1.73 m2 had a higher prevalence of CAD (66.8% vs. 72.9% and 80.1%, respectively; p = 0.001) and three-vessel CAD (25.6% vs. 34.5% and 39.5%, respectively; p = 0.001). At 36 months of follow-up, patients with an eGFR 30-<60 mL/min/1.73 m2 and eGFR < 30 mL/min/1.73 m2 suffered from significantly higher risk of HF-associated rehospitalization (HR = 1.937, 95% CI: 1.739-2.157, p = 0.001 and HR = 3.223, 95% CI: 2.743-3.787, p = 0.001, respectively) and AMI compared to patients with an eGFR ≥ 60 mL/min/1.73 m2 (reference group). The significantly higher risk of HF-related rehospitalization remained after multivariable adjustment. Conclusions: Both groups with impaired kidney function demonstrated a markedly higher risk of rehospitalization for HF at 36 months-even after multivariate adjustments. Increased risk of HF-related rehospitalization in patients with an eGFR < 30 mL/min/1.73 m2 was especially evident if they also presented with decompensated HF and LVEF < 35%. In patients with an eGFR 30-<60 mL/min/1.73 m2, presenting with angina pectoris and multivessel disease increased the risk of HF-related rehospitalization.
PMID:40507513 | PMC:PMC12155580 | DOI:10.3390/jcm14113753
Chin Med. 2025 Jun 13;20(1):86. doi: 10.1186/s13020-025-01128-8.
ABSTRACT
BACKGROUND: The heart, as the body's blood-pumping organ, is extremely sensitive to changes in oxygen levels. Myocardial injury caused by hypoxia is a challenging issue, and there are currently no definitive specific drugs available for its treatment. Ginsenoside Rg5, one of the main rare saponins in ginseng, has shown significant efficacy in treating myocardial injury. This study aims to investigate the role and mechanisms of Rg5 in the treatment of hypoxic myocardial injury.
METHODS: The cardioprotective effect against acute hypoxia of Rg5 was studied by assessing heart function, myocardial injury markers, inflammation, and oxidative stress in C57 mice, as well as apoptosis and reactive oxygen species (ROS) levels in H9c2 cardiomyocytes. Thermal proteome and target validation techniques were used to confirm the target protein of Rg5. The further protective mechanisms against hypoxia-induced damage were explored using immunocoprecipitation, immunofluorescence and rescue experiments in vivo and in vitro.
RESULTS: The experimental results demonstrated that Rg5 effectively improved cardiac function in mice, reduced inflammation, oxidative stress, and the release of myocardial injury markers, decreased cardiomyocyte apoptosis, and lowered ROS levels. Further, using target protein screening and validation techniques, Signal transducer and activator of transcription 3 (STAT3) was verified as a direct target for Rg5's cardioprotective effect. It was observed that Rg5 specifically promoted the phosphorylation of Tyr705 in STAT3 via the JAK2/STAT3 pathway, leading to the translocation of phosphorylated STAT3 into the nucleus where they induce the expression of anti-apoptotic protein and protect cells from hypoxic damage.
CONCLUSION: Rg5 could be a potential therapeutic agent for preventing and treating myocardial hypoxic injury, providing scientific evidence for its application in anti-hypoxic therapy.
PMID:40514732 | PMC:PMC12166643 | DOI:10.1186/s13020-025-01128-8
J Nanobiotechnology. 2025 Jun 13;23(1):439. doi: 10.1186/s12951-025-03474-z.
ABSTRACT
BACKGROUND: Acute myocardial infarction remains a leading cause of mortality, with ischemia-reperfusion (I/R) injury causing severe myocardial damage through mitochondrial dysfunction. While mesenchymal stem cell-derived exosomes (MSC-Exo) show therapeutic potential, their limited targeting and insufficient mitochondrial protection restrict clinical application.
RESULTS: We developed a novel engineered exosome platform (Exo-I-S) using an IRES-driven bicistronic plasmid to co-load Sirtuin3 (SIRT3) and GPI-Insulin, aiming to enhance targeting efficiency and mitochondrial protection. The platform was evaluated in both in vitro and in vivo models of myocardial I/R injury. In vitro, Exo-I-S achieved faster cellular uptake, improved mitochondrial function, and reduced oxidative stress in H9c2 cells. The platform activated PI3K/AKT signaling, enhanced Glut4 translocation, and improved mitochondrial respiratory capacity. In a rat I/R injury model, Exo-I-S significantly reduced infarction size, improved cardiac function, and enhanced glucose metabolism, with superior therapeutic outcomes compared to unmodified exosomes.
CONCLUSIONS: The dual functionality of Exo-I-S, combining insulin-mediated targeting with SIRT3-driven mitochondrial protection, provides a promising strategy for I/R injury treatment. Future studies should focus on optimizing targeting specificity and developing sustained release mechanisms to enhance clinical applicability.
PMID:40514650 | PMC:PMC12164078 | DOI:10.1186/s12951-025-03474-z
Nat Cardiovasc Res. 2025 Jun;4(6):761-772. doi: 10.1038/s44161-025-00657-7. Epub 2025 Jun 13.
ABSTRACT
Data on the cardiovascular-kidney effects and safety of empagliflozin among patients with acute myocardial infarction are limited. EMPACT-MI (Study to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) was a double-blind, multicenter clinical trial that randomized 6,522 patients with acute myocardial infarction and risk for heart failure to empagliflozin or placebo. Here we show in this secondary analysis that the mean estimated glomerular filtration rate at baseline was 76.1 ml min-1 1.73 m-2 (s.d. = 19.9 ml min-1 1.73 m-2), with longitudinal kidney function data available for 1,152 (17.7%) treated patients from select countries. By 24 months, compared with baseline, the estimated glomerular filtration rate was similar in the empagliflozin group but declined in the placebo group (P = 0.01). Empagliflozin reduced the total adverse events of heart failure or all-cause mortality irrespective of kidney function (Pinteraction = 0.30). Thirty-day adverse event rates were similar by treatment group and consistent across baseline kidney function. Empagliflozin had kidney-protective effects, reduced heart failure outcomes and was safe to initiate soon after acute myocardial infarction across baseline kidney function.
PMID:40514435 | PMC:PMC12170341 | DOI:10.1038/s44161-025-00657-7
Cell Transplant. 2025 Jan-Dec;34:9636897251347389. doi: 10.1177/09636897251347389. Epub 2025 Jun 13.
ABSTRACT
Myocardial ischemia-reperfusion injury (MIRI), which occurs when the blood supply is restored in the ischemic myocardium, is a major medical concern for patients with acute myocardial infarction (AMI). Despite the use of extracellular vesicles (EVs) from mesenchymal stromal cells (MSCs), which can be used to treat MIRI, the application of EVs still has limited use in clinical practice. Melatonin (MT), however, not only exerts a significant protective effect in the treatment of cardiovascular diseases but also enhances biological functions of MSCs through pretreatment. Therefore, in the current study, we sought to determine whether MT improves the paracrine effect of MSCs through pretreatment. Our research provides evidence to support the therapeutic effect of MT-pretreated MSCs-derived extracellular vesicles (MT-EVs) in ameliorating hypoxia/reoxygenation (H/R) injury in human umbilical vein endothelial cells (HuVECs). We also performed a metabolomic analysis using ultra-high-performance liquid chromatography/Q Exactive HF-X Hybrid Quadrupole-Orbitrap Mass (UHPLC-QE-MS/MS) to explore metabolism profiling of H/R cell model with MT-EVs or EVs from MSCs (NC-EVs) treatment. We found 932 differential metabolites (DEMs) in the MT-EVs group compared with the NC-EVs group. Metabolic profiling analysis showed these metabolites were engaged in the ABC transporters, nucleotide metabolism, purine metabolic pathway, and glycerophospholipid metabolism. Furthermore, we observed increased levels of palmitoylcarnitine (fatty acid-derived mitochondrial substrate) and gabapentin in the MT-EVs group, which may play a therapeutic role in HuVECs during H/R. In conclusion, the results demonstrated that MT-EVs can protect endothelial cells from H/R injury by affecting the metabolic pathways.
PMID:40514195 | PMC:PMC12171273 | DOI:10.1177/09636897251347389
Metabolism. 2025 Jun 11;170:156326. doi: 10.1016/j.metabol.2025.156326. Online ahead of print.
ABSTRACT
Ubiquitin-specific protease 48 (USP48) plays an important role in the regulation of DNA repair and immune signaling in health and diseases. Nonetheless, its implication in the development of diabetes-accelerated myocardial ischemia/reperfusion (I/R) injury (MI/RI) has yet to be clarified. Diabetic mice were constructed by streptozotocin (STZ) injection, and MI/RI was then induced by coronary artery occlusion and reperfusion. H9c2 cells were exposed to high glucose (HG) for 24 h, followed by hypoxia/reoxygenation (H/R) for 4 and 2 h, respectively. USP48 protein and mRNA levels were downregulated in MI/RI mice or H/R-exposed cardiomyocytes, but were unexpectedly upregulated in diabetic mice following MI/RI and H9c2 cells exposed to HG and H/R. Cardiac-specific deficiency of USP48 worsened cardiac dysfunction, increased post-ischemic infarction size, promoted mitochondrial damage in myocardial cells, accelerated cardiomyocyte inflammation, oxidative stress, and apoptosis in diabetic mice. Conversely, such pathological conditions were ameliorated by cardiac-specific overexpression of USP48. Proteomics and experimental validation showed that USP48 stabilized and upregulated calponin 1 (CNN1) to confer cardioprotection, since silencing CNN1 minimized the benefits of USP48 in diabetes-aggravated cardiomyocyte injury. RNA sequencing and experimental data demonstrated that the USP48/CNN1 axis inhibited the release of CXC motif chemokine ligand 1 (CXCL1) and CXCL2 through inactivating the ERK1/2 pathway. Eventually, blockade of CXCL1/2 with specific antibodies protected against diabetes-exacerbated MI/RI, akin to USP48 overexpression. Together, these results highlight USP48 as a potential therapeutic target for managing diabetes-aggravated MI/RI by regulating the CNN1/ERK1/2/CXCL1/2 signaling pathway.
PMID:40513941 | DOI:10.1016/j.metabol.2025.156326
Biochim Biophys Acta Mol Cell Res. 2025 Jun 11;1872(7):120006. doi: 10.1016/j.bbamcr.2025.120006. Online ahead of print.
ABSTRACT
OBJECTIVE: The present study aimed to investigate the role of delphinidin (Dp) in myocardial ischemia-reperfusion injury (MIRI) and elucidate the underlying mechanism.
METHODS: MIRI animal models were established in Sprague-Dawley rats by ligation of left anterior descending coronary artery (LAD) ligation for 30 min and reperfusion of 2 h. Primary cardiomyocytes and H9C2 cells were stimulated by oxygen-glucose deprivation/regain (OGD/R) conditions for mimicking MIRI cell models. Ultrasound, hematoxylin and eosin and Masson staining were used to evaluate cardiac function and myocardial infarction in rats following Dp treatment. Cell counting kit-8 assay and flow cytometry were performed to detect cell viability and apoptosis, respectively. Western blotting and quantitative real-time polymerase chain reaction measured ALOX15 expression. Additionally, ferroptosis-related factors and lactate dehydrogenase levels were detected using commercial kits.
RESULTS: In MIRI rats, Dp treatment dose-dependently increased the left ventricular ejection fraction (EF) and fractional shortening (FS) while reduced the left ventricular internal diameter in diastole (LVIDd) and systole (LVIDs). The increase of necrosis and fibrosis in cardiac tissues of MIRI rats were relieved by Dp. Dp treatment inhibited the apoptosis and ferroptosis of cardiomyocytes both in vivo and in vitro. Mechanically, Dp docked with a ferroptosis-related protein ALOX15 to induce its degradation. Moreover, ferroptosis activator erastin and ALOX15 overexpression reversed the protective effects of Dp on cardiomyocytes.
CONCLUSION: Dp inhibited ferroptosis by molecular docking ALOX15 and inducing its degradation, thereby improving MIRI.
PMID:40513616 | DOI:10.1016/j.bbamcr.2025.120006
Chin J Integr Med. 2025 Jun 13. doi: 10.1007/s11655-025-4017-4. Online ahead of print.
ABSTRACT
OBJECTIVE: To investigate cisplatin-induced cardiovascular toxicity and explore the protective effects and potential mechanism of curcumin co-treatment.
METHODS: Forty adult male Sprague-Dawley rats were numbered and randomly divided into control group, cisplatin group (7.5 mg/kg, once a week, for 2 weeks), curcumin group (200 mg/kg per day, for 2 weeks) and cisplatin+curcumin group (cisplatin 7.5 mg/kg, once a week, and curcumin 200 mg/kg per day for 2 weeks) by a random number table method, with 10 rats in each group. Cardiac and vascular morphology and functions were assessed using hematoxylin-eosin and Masson's trichrome staining, serum indexes detection, echocardiography, electrocardiogram (ECG), blood pressure monitoring, vascular ring isometric tension measurement, and left ventricular pressure evaluation. The expressions of extracellular signal-regulated kinases (ERK) and phosphorylated-ERK (p-ERK) were analyzed by immunohistochemical staining.
RESULTS: Cisplatin treatment induced notable cardiac alteration, as evidenced by changes in cardiac morphology, elevated serum enzymes (P<0.05), ECG abnormalities, and increased left ventricular end-diastolic pressure (P<0.05). Meanwhile, cisplatin significantly increased arterial pulse pressure (P<0.01), primarily due to a decrease in diastolic blood pressure. Severe fibrosis was also observed in the thoracic aorta wall. In vascular ring experiments, cisplatin treatment led to a significant reduction in phenylephrine-induced contraction (P<0.05) and acetylcholine-induced relaxation (P<0.01). Notably, Curcumin co-administration significantly alleviated cisplatin-induced cardiovascular damages, as demonstrated by improvement in these parameters. Furthermore, ERK expression in the myocardium and p-ERK expression in vascular smooth muscle cells were significantly upregulated following curcumin co-treatment.
CONCLUSIONS: Curcumin protects the heart and vasculature from cisplatin-induced damages, likely by upregulating ERK/p-ERK expression. These findings suggest that curcumin may serve as a promising therapeutic strategy for mitigating cisplatin-associated cardiovascular toxicity during tumor chemotherapy. In vitro cell culture experiments are needed to clarify the underlying mechanism.
PMID:40512365 | DOI:10.1007/s11655-025-4017-4
Cell Mol Life Sci. 2025 Jun 13;82(1):232. doi: 10.1007/s00018-025-05741-6.
ABSTRACT
OBJECTIVE: In this study, we sought to determine the significant impact of the vascular endothelial endoplasmic reticulum (ER) stress C/EBP homologous protein (CHOP) in renovascular hypertension-induced vascular endothelial dysfunction and cardiac fibrosis.
APPROACH AND RESULTS: Eight-week-old male and female CHOPflox/flox and ECCHOP-/- mice were randomly divided into eight groups with and without 2-Kidney-1-Clip (2K1C) surgery for four weeks. Body weight, systolic blood pressure, running performance, cardiac hypertrophy and fibrosis, lung edema, inflammation, vascular endothelial function, and signaling were assessed. For the mechanism, we utilized human coronary endothelial cells, both with and without CHOP down-regulation, and then stimulated them with and without angiotensin II ± ATP to determine eNOS phosphorylation level and the presence of inflammatory factors. Male and female CHOPflox/flox mice subjected to 2K1C for four weeks exhibited hypertension, cardiac hypertrophy and fibrosis, lung edema, impaired running performance, endothelium-dependent vascular relaxation dysfunction, reduction in eNOS phosphorylation, and inflammation induction. In contrast, male and female ECCHOP-/- mice subjected to 2K1C for four weeks were protected against the pathogenesis of renovascular hypertension. In vitro, data showed that deletion of CHOP in endothelial cells protected eNOS phosphorylation level and blunted the induction of inflammation in response to angiotensin II ± ATP.
CONCLUSION: Our research findings determined that CHOP is a central mechanism driving vascular endothelial dysfunction and cardiac fibrosis in renovascular hypertension. Therefore, targeting CHOP in endothelial cells could be a potential therapeutic approach to protect against the pathogenesis of renovascular hypertension.
PMID:40512182 | PMC:PMC12165939 | DOI:10.1007/s00018-025-05741-6
Molecules. 2025 May 31;30(11):2425. doi: 10.3390/molecules30112425.
ABSTRACT
The genus Clinopodium L. (Lamiaceae) comprises perennial herbaceous plants known for their diverse pharmacological properties. Clinically, these plants are mainly used for the treatment of various hemorrhagic disorders. This review systematically summarizes the research progress on the chemical composition, pharmacological activity, quality control, toxicity, and pharmacokinetics of the genus Clinopodium by searching Google Scholar, Scopus-Elsevier, Wiley, Springer, Taylor & Francis, Medline, Web of Science, CNKI, Weipu, Wanfang, and other academic databases over the last decade (March 2015-February 2025). To date, more than one hundred and thirty structurally diverse secondary metabolites have been isolated and identified from this genus, including flavonoids, triterpenoid saponins, diterpenoid glycosides, lignans, and phenylpropanoids. In addition, numerous volatile oil constituents have been identified in over forty species of the genus Clinopodium. Crude extracts and purified compounds exhibit a variety of pharmacological activities, including hemostatic, anti-myocardial cell injury, cardiovascular protective, anti-inflammatory, antimicrobial, antitumor, hypoglycemic, and insecticidal properties. However, current quality assessment protocols in the genus Clinopodium are limited to flavonoid- and saponin-based evaluations in C. chinense (Benth.) O. Kuntze and C. gracile (Benth.) O. Matsum. Further research is needed to elucidate the pharmacological mechanisms, toxicity, and possible interactions with other drugs. Therefore, the genus Clinopodium has a wide range of biologically active compounds with potential applications in drug development for hemostasis and cardiovascular protection. Nevertheless, there is also an urgent need to establish standardized methodologies to address uncertainties concerning the safety and efficacy of injectable extracts or compounds.
PMID:40509312 | PMC:PMC12156807 | DOI:10.3390/molecules30112425
J Clin Med. 2025 Jun 3;14(11):3947. doi: 10.3390/jcm14113947.
ABSTRACT
Background/Objectives: The complement system (particularly C5b-9) is an instrumental part of the induction and progression of atherosclerosis. The fluid phase C5b-9, also known as soluble C5b-9 (sC5b-9), is a reliable indicator of terminal complement pathway activation. Response Gene to Complement (RGC)-32 is a C5b-9 effector involved in cell cycle regulation and differentiation, immunity, tumorigenesis, obesity, and vascular lesion formation. RGC-32 regulates the expression of Sirtuin1 (SIRT1), known to delay vascular aging. The aim of this study was to assess the levels of sC5b-9, RGC-32, and SIRT1 in patients with atherosclerotic chronic and acute ischemic coronary syndromes. Methods: We determined the levels of sC5b-9, serum RGC-32, and SIRT1 by enzyme-linked immunosorbent assays (ELISAs) in 41 patients with chronic atherosclerotic coronary syndromes, 36 patients with acute ischemic coronary syndromes, and 21 asymptomatic controls with no history of ischemic heart disease. Results: sC5b-9 was significantly higher in patients with acute coronary syndrome as compared to the control group (p = 0.020, AUC = 0.702). In chronic coronary ischemia patients, serum RGC-32 was correlated with the extension of coronagraphically visualized atherosclerotic lesions (r = 0.352, p = 0.035) as well as with sC5b-9 levels (r = 0.350, p = 0.025). RGC-32 concentration was significantly lower in patients with acute coronary syndrome than in the control group (p = 0.020). We also observed significantly lower serum SIRT1 concentrations in patients with chronic ischemic heart disease than in the control group (p = 0.025). Conclusions: sC5b-9 may function as a possible biomarker for myocardial tissue damage in acute coronary syndrome. In acute coronary syndrome settings, low levels of RGC-32 may indicate a protective, antifibrotic function of RGC-32 in the ischemia-damaged myocardium; however, in stable chronic disease, RGC-32 serum values appear to correlate with the extent of atherosclerotic lesions, suggesting a pro-atherogenic role for RGC-32. Chronic myocardial ischemia decreases SIRT1 protein levels in serum, which underscores the use of SIRT1-modulating drugs in these patients.
PMID:40507709 | PMC:PMC12156031 | DOI:10.3390/jcm14113947
J Thorac Cardiovasc Surg. 2025 Jun 11:S0022-5223(25)00472-6. doi: 10.1016/j.jtcvs.2025.06.005. Online ahead of print.
ABSTRACT
OBJECTIVES: The mechanisms underlying anatomical tricuspid regurgitation (TR) in congenitally corrected transposition of the great arteries (ccTGA) remain unclear. This study investigated the association between interventricular septal motion (IVSm) and TR severity.
METHODS: Echocardiographic data from 406 ccTGA patients were retrospectively analyzed and stratified by TR grade (≥3 vs. ≤2) at initial evaluation. IVSm was categorized as normal, reversed, or bidirectional. Patients who underwent pulmonary artery banding (PAB) and those with TR grade ≤2 without prior surgery were analyzed as separate subgroups.
RESULTS: Among 109 patients with TR grade ≥3, 91 (83.49%) had reversed IVSm, significantly higher than in the ≤2 group (6/297, 2.02%). In the PAB subgroup (n=79), TR severity significantly decreased post-procedure (P<0.001), accompanied by a shift in IVSm from reversed to normal (P<0.001). In the no-surgery group (n=136), Fourteen patients (10.29%) developed progressive TR and right ventricular dilation secondary to the reversal of IVSm. Reversed IVSm was a strong predictor of severe TR (AUC 0.77, P=0.001) and independently associated with its development (HR 28.35, P<0.001).
CONCLUSIONS: Reversed IVSm is significantly associated with severe TR in ccTGA and may act as both a mechanistic contributor and a predictive marker of disease progression.
PMID:40513814 | DOI:10.1016/j.jtcvs.2025.06.005
Anaesth Crit Care Pain Med. 2025 Apr 24;44(4):101528. doi: 10.1016/j.accpm.2025.101528. Online ahead of print.
NO ABSTRACT
PMID:40513495 | DOI:10.1016/j.accpm.2025.101528
J Int Med Res. 2025 Jun;53(6):3000605251348230. doi: 10.1177/03000605251348230. Epub 2025 Jun 13.
ABSTRACT
Accessory mitral valve tissue is a rare congenital cardiac anomaly that can lead to left ventricular outflow tract obstruction. We present the case of an older female patient with accessory mitral valve tissue, a subaortic membrane, an unruptured aneurysm of the aortic sinus, and left ventricular outflow tract obstruction. Successful excision of the accessory mitral valve tissue and repair of the aortic sinus were performed. Postoperative echocardiography showed complete removal of the subaortic membrane, with a residual accessory mitral valve tissue (5 mm). Color Doppler imaging revealed a significant reduction in mosaic flow signals in the left ventricular outflow tract, with the peak blood flow velocity decreasing to 1.6 m/s. The postoperative course was uneventful, and the patient was followed up with echocardiography at 3 days, 5 days, 1 month, 3 months, and 6 months after the surgery. Accessory mitral valve tissue is a rare congenital defect frequently associated with other cardiovascular congenital malformations. This report also provides a comprehensive clinical review of accessory mitral valve tissue, covering anatomical classification, associated cardiac anomalies, pathophysiology, diagnostic approaches, and treatment strategies to offer an improved clinical understanding of the condition.
PMID:40511724 | PMC:PMC12171269 | DOI:10.1177/03000605251348230
Cureus. 2025 May 13;17(5):e84002. doi: 10.7759/cureus.84002. eCollection 2025 May.
ABSTRACT
Intraoperative cardiac arrest during pediatric congenital heart disease surgery is rare but associated with high mortality and poor neurological outcomes. While cerebral perfusion during cardiopulmonary resuscitation is typically antegrade, retrograde cerebral flow has not been reported. We report a case of a 12-year-old girl undergoing pulmonary artery debanding for congenitally corrected transposition of the great arteries. Massive hemorrhage from pulmonary artery injury led to cardiac arrest, during which antegrade cerebral flow was likely absent for 15 minutes. Nevertheless, the patient recovered without neurological sequelae. Time-domain near-infrared spectroscopy showed increased deoxygenated hemoglobin and preserved total hemoglobin, suggesting cerebral perfusion via retrograde venous flow. Central venous pressure was maintained at 15-25 mmHg through rapid transfusion. This case suggests that retrograde cerebral perfusion may occur during cardiac arrest when central venous pressure is adequately maintained, potentially contributing to favorable neurological outcomes even in the absence of antegrade flow.
PMID:40510082 | PMC:PMC12159692 | DOI:10.7759/cureus.84002