Search Results (81)

Allium chinense G. Don is valued for its edible and medicinal qualities. It has been reported that Allium chinense has the potential to inhibit platelet activation, but its mechanism of action is unknown, which needs to be further explored. This study investigates the anti-myocardial ischemia–reperfusion (I/R) injury potential of Allium chinense from the perspective of platelet activation, focusing on its chemical composition and underlying mechanisms of action. A combination of transcriptome sequencing, molecular docking, and experimental validation was employed in our study. The antiplatelet active fraction MT-95ET of Allium chinense was screened by the ADP-induced platelet aggregation model in vitro. In vivo experiments demonstrated that MT-95ET can reduce the myocardial injury of I/R rats and inhibit I/R-induced platelet activation, adhesion, and aggregation. UHPLC-Q-Orbitrap-MS/MS was used to identify 13 compounds from MT-95ET. Transcriptome sequencing and molecular docking identified aerobic glycolysis key checkpoints PDK1 and PKM2 as key targets, with Sarsasapogenin and Hecogenin exhibiting strong binding affinities to these proteins. Western blot analysis further validated that MT-95ET downregulated PKM2 and PDK1, indicating a possible mechanism for its antiplatelet effects and anti-myocardial I/R injury. Full article

Background/Objectives: To evaluate the prognostic role of the inflammatory prognostic index (IPI) value at admission in major adverse cardiovascular and cerebrovascular events (MACCEs) in individuals with non-ST elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI). Methods: A total of 1142 NSTEMI patients with a mean age of 61.9 ± 12.5 years were included. Admission C-reactive protein level, serum albumin level, and complete blood counts of participants were collected from hospital records. The IPI was calculated based on the following formula: C-reactive protein/albumin ratio (CAR) x neutrophil-to-lymphocyte ratio (NLR). An aggregate index of systemic inflammation (AISI) value was calculated using the ‘‘neutrophil count x monocyte count x platelet/lymphocyte count’’ formula. The study cohort was divided into two groups according to the median IPI value. Results: Patients with higher IPI values were statistically more likely to suffer from MACCEs within one year (p < 0.001), thus the admission IPI value was found to be associated with future development of MACCEs. Furthermore, it had sufficient discrimination power (AUC = 0.70) and predictive accuracy in identifying MACCEs compared to other inflammatory parameters such as the CAR (AUC = 0.64), the NLR (AUC = 0.64), and the AISI (AUC = 0.59). Adding the IPI to the baseline multivariable logistic regression model significantly improved the model’s discrimination and net clinical benefit effect for identifying patients who would suffer from MACCEs, with a C-index of 0.84 (95% CI: 0.82–0.86) and explanatory power of 23.2% (R² = 0.232, DeLong test p = 0.001). High-risk patients with an IPI value greater than 2.43 had significantly more adverse events (p < 0.001). Conclusions: The IPI may be a promising inflammatory index for use in clinical practice to determine the risk prediction of MACCEs in NSTEMI patients undergoing PCI. Full article

Background: Myocardial infarction complicated by cardiogenic shock (MI-CS) remains a critical condition with high mortality rates, despite advances in treatment. Systemic inflammation plays a significant role in MI-CS progression; however, its dynamics across different stages of the Society for Cardiovascular Angiography and Interventions (SCAI) classification remain poorly understood. This study aimed to evaluate indices of systemic inflammation—neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI)—in MI-CS patients, correlating them with SCAI stages and survival outcomes. Methods: A single-center retrospective study included 132 patients with MI-CS, categorized into SCAI stages A–E. All patients were assessed for demographic, clinical, and laboratory data, procedural and treatment characteristics, MI timing, and outcomes. Complete blood count test data were used to calculate inflammatory indices and evaluate types of immune reactions. Results: PLR, SII, and AISI peaked at SCAI stage C and declined significantly at stage E, suggesting suppressed inflammation in advanced shock. SIRI emerged as a key prognostic marker for stage C patients, with elevated levels associated with larger infarct size, higher heart rate, and predominant innate immune activation. Patients with SIRI ≥ 3.34 had significantly lower two-year survival (log-rank test, p = 0.006). Conclusions: Inflammation indices, particularly SIRI, provide valuable prognostic insights in MI-CS, reflecting disease severity and heterogeneity of immune response. The decline in inflammatory indices at SCAI stage E may indicate immune suppression in extreme MI-CS, underscoring the need for personalized therapeutic strategies. Full article

Both cardiac and skeletal muscles originate from the mesoderm, although the two tissues develop from distinct primordia within the early embryo. The shared, albeit distinctive muscle phenotype of these two cell types have led many researchers to investigate whether stem cells from adult skeletal muscle have the capacity to generate cells with a contractile, cardiac phenotype. To date, most of those studies have relied on multistep protocols requiring tissue engineering, co-cultures or transplantation experimentation. In this report, we describe a simple, cell culture method for obtaining contractile, cardiogenic aggregates from skeletal muscle-derived stem cells (MDSCs). Combining in vitro conditions used for promoting the differentiation of cardiac progenitor cells and the long-term maintenance of heart tissue fragments, we have been able to convert MDSCs to myocardial cells that aggregate into beating myospheres. These selective and optimized culture conditions continued to support a contractile cardiogenic phenotype for over four months in vitro. This culture protocol provides a model for future insights into the pathways responsible for the divergence of skeletal and cardiac phenotypes, as well as a source of easily obtained myocardial tissue for subsequent scientific investigations into cardiac function and biology. Full article

Microvascular ischemia, especially in the heart and kidneys, is associated with inflammation and metabolic perturbation, resulting in cellular dysfunction and end-organ failure. Heightened production of adenosine from extracellular nucleotides released in response to inflammation results in protective effects, inclusive of adaptations to hypoxia, endothelial cell nitric oxide release with the regulation of vascular tone, and inhibition of platelet aggregation. Purinergic signaling is modulated by ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1)/CD39, which is the dominant factor dictating vascular metabolism of extracellular ATP to adenosine throughout the cardiovascular tissues. Excess levels of extracellular purine metabolites, however, have been associated with metabolic and cardiovascular diseases. Physiological estrogen signaling is anti-inflammatory with vascular protective effects, but pharmacological replacement use in transgender and postmenopausal individuals is associated with thrombosis and other side effects. Crucially, the loss of this important sex hormone following menopause or with gender reassignment is associated with worsened pro-inflammatory states linked to increased oxidative stress, myocardial fibrosis, and, ultimately, diastolic dysfunction, also known as Yentl syndrome. While there is a growing body of knowledge on distinctive purinergic or estrogen signaling and endothelial health, much less is known about the relationships between the two signaling pathways. Continued studies of the interactions between these pathways will allow further insight into future therapeutic targets to improve the cardiovascular health of aging women without imparting deleterious side effects. Full article

Capecitabine (CAP) is one of the most commonly prescribed fluoropyrimidines in oncology, especially in the treatment of colon cancer. Cardiac toxicity is a severe and potentially lethal adverse drug reaction (ADR) against fluoropyrimidines. Cardiac ADRs, such as myocardial infarction (MI), heart failure (HF), arrhythmias, and a number of cardiomyopathies, are reported for these molecules. To have a better understanding of the risk–benefit ratio of colon cancer therapy, a pharmacovigilance study of real-world evidence of the cardiac toxicity of antineoplastic agents is required. Aim: This post-marketing research on CAP aims to assess the risk of cardiac toxicity. Five other antitumor drugs used in colorectal cancer, i.e., 5-fluorouracil (5-FU), irinotecan (IRI), oxaliplatin (OX), bevacizumab (BEV) and panitumumab (PAN), were also studied to create a relative profile of observed cardiotoxicity. Methods: A retrospective study based on reports submitted in the EudraVigilance (EV) database until 28 July 2024 was conducted. Using the aggregated data from EV, a descriptive analysis and disproportionality analysis of cardiac ADRs induced by fluoropyrimidines were performed. To evaluate the disproportionality of the signals, Reporting Odds Ratio (ROR) and 95% confidence interval (95% CI) were calculated by comparison with other drugs used in colorectal cancer: 5-FU, IRI, OX, BEV, and PAN. Results: “Cardiac disorders” represent 3.4% of the total reports for CAP. The value is comparable to 5-FU, but higher than for other drugs. t was observed that there are no significant differences in the occurrence of cardiac ADRs in patients exposed to CAP and 5-FU treatments, and in particular MI and HF. Compared to 5-FU, which could produce cardiac arrythmias with a higher probability than all other drugs, CAP has a higher probability of reporting this ADR only in comparison with IRI (ROR: 1.2971; 95% CI: 1.0196-1.6502). Conclusions: CAP induces adverse cardiovascular reactions, especially MI, HF, and cardiomyopathies. Arrhythmias have been shown to be side effects more frequent associated with 5-FU than with CAP. The results emphasize the need for a rigorous cardiovascular monitoring of patients following treatment with CAP or 5-FU and especially for those with pre-existing cardiac pathology. Full article

Background: Surgery often leads to bleeding associated with hypofibrinogenemia. Supplementation with fibrinogen concentrate appears to be effective and safe, although findings from studies are inconsistent. The primary aim of this study was to assess the safety of fibrinogen concentrate during the perioperative period. Methods: This single-centre, prospective, observational study included adult patients undergoing scheduled or emergency surgery related to bleeding coagulopathy and the administration of fibrinogen concentrate. Patients were followed until their discharge from the institution. Comprehensive data were collected, including age, sex, type of surgery, associated comorbidities, anticoagulant and/or anti-aggregating therapy, and the number of blood transfusions. Laboratory data on plasma fibrinogen concentration, haemoglobin, and platelet count before and after surgery were also collected. The primary outcomes were the mortality rate at discharge and any reported thrombotic or thromboembolic events, including deep vein thrombosis, pulmonary embolism, and myocardial infarction. Results: The study included 91 adult patients who had undergone surgery, with 29 surgeries (32%) conducted in an emergency setting. The mean age was 59.2 years, and 53.8% were male. Major bleeding occurred in 29 cases, mainly in older males and those on anticoagulant therapy. The pre-operative fibrinogen level averaged 161 mg/dL, and the average dosage of fibrinogen concentrate administered was 2.7 g. Eight patients died (8.8%), mostly due to septic or cardiogenic shock, with deaths being more frequent in emergency settings. Thromboembolic events occurred in eight patients, none of whom died. No additional adverse events directly related to the administration of fibrinogen concentrate were reported. Conclusions: Our findings suggest a favourable safety profile for fibrinogen concentrate in surgical patients, as evidenced by a low incidence of deaths and thromboembolic events, which were primarily attributed to other factors. Future research should strive to increase statistical robustness to further illuminate clinically significant patient safety measures. Full article

Background: 4-MDMB-BUTINACA, a next-generation synthetic cannabinoid, presents significant public health and forensic challenges due to its evolving nature and potential toxicity. Methods: This study evaluates the subacute toxic effects and pharmacokinetics of 4−Fluoro MDMB−BUTINACA (4F-MDMB-BUTINACA) in adult male albino rats, administered orally for seven days at doses of 1 mg/kg, 5 mg/kg, and 15 mg/kg. The hematological, biochemical, and histopathological parameters were assessed and compared to controls. Results: The pharmacokinetics were determined using GC–MS/MS with a positive chemical ionization and granisetron as an internal standard. A histological analysis revealed inflammatory cell aggregation, congestion, hemorrhage, edema, and fibrosis in various tissues, with renal examinations showing tubule degradation, glomerular atrophy, Bowman’s space expansion, edema, and hemorrhage. The liver exhibited cellular infiltration, while cardiac muscle fibers showed myocardial fiber degradation and inflammatory cell aggregation. Biochemical assays indicated significant alterations (p < 0.05) in the serum levels of AST, ALT, ALP, GGT, total protein, albumin, triglycerides, urea, MCHC, MCV, RDW, platelets, neutrophils, eosinophils, and basophils compared to the controls. Conclusions: The validated bioanalytical method revealed rapid absorption of 4F-MDMB-BUTINACA, with a plasma half-life of 2.371 h, a volume of distribution of 2272.85 L, and a plasma clearance rate of 664.241 L/h. In conclusion, 4F-MDMB-BUTINACA is a highly toxic synthetic cannabinoid, particularly affecting the liver, kidneys, and heart. Full article

Cardiovascular disease is a leading cause of morbidity and mortality. New research elucidates increasingly complex relationships between cardiac and metabolic health, giving rise to new possible therapeutic targets. Sphingolipids are a heterogeneous class of bioactive lipids with critical roles in normal human physiology. They have also been shown to play both protective and deleterious roles in the pathogenesis of cardiovascular disease. Ceramides are implicated in dysregulating insulin signalling, vascular endothelial function, inflammation, oxidative stress, and lipoprotein aggregation, thereby promoting atherosclerosis and vascular disease. Ceramides also advance myocardial disease by enhancing pathological cardiac remodelling and cardiomyocyte death. Glucosylceramides similarly contribute to insulin resistance and vascular inflammation, thus playing a role in atherogenesis and cardiometabolic dysfunction. Sphingosing-1-phosphate, on the other hand, may ameliorate some of the pathological functions of ceramide by protecting endothelial barrier integrity and promoting cell survival. Sphingosine-1-phosphate is, however, implicated in the development of cardiac fibrosis. This review will explore the roles of sphingolipids in vascular, cardiac, and metabolic pathologies and will evaluate the therapeutic potential in targeting sphingolipids with the aim of prevention and reversal of cardiovascular disease in order to improve long-term cardiovascular outcomes. Full article

Anterior myocardial infarction is a critical condition with significant implications for cardiac function and patient prognosis. Despite advancements in reperfusion therapies, optimizing recovery during the early phases of myocardial infarction remains challenging. Anterior myocardial infarction can lead to substantial long-term effects on a patient’s health due to extensive damage to the heart muscle, particularly the left ventricle, impacting both quality of life and overall prognosis. Vericiguat, a soluble guanylate cyclase stimulator, has shown promise in heart failure, but its role in early anterior myocardial infarction has not yet been fully explored. By enhancing soluble guanylate cyclase activity, vericiguat may increase cyclic guanosine monophosphate production, leading to vasodilation, inhibition of platelet aggregation, and potential cardioprotective effects. Currently, treatment options for anterior myocardial infarction primarily focus on reperfusion strategies and managing complications. However, there is a critical need for adjunctive therapies that specifically target the pathophysiological changes occurring in the early phases of myocardial infarction. Vericiguat’s mechanism of action offers a novel approach to improving vascular function and myocardial health, potentially contributing to innovative treatment strategies that could transform the care and prognosis of patients with anterior myocardial infarction. Full article

Objectives: To document the real-world experience with the use of pneumatic pulsatile mechanical circulatory support (MCS) with the PulseCath iVAC2L during high-risk percutaneous coronary interventions (HR-PCIs). Background: The use of MCS in HR-PCIs may reduce the rate of major adverse cardiovascular events (MACEs) at 90 days. The PulseCath iVAC2L is a short-term pulsatile transaortic left ventricular (LV) assist device that has been in use since 2014. The iVAC2L Registry tracks its safety and efficacy in a variety of hospitals worldwide. Methods: The iVAC2L Registry is a multicenter, observational registry that aggregates clinical data from patients treated with the iVAC2L worldwide. A total of 293 consecutive cases were retrospectively collected and analyzed. Estimated rates of in-hospital clinical endpoints were described. All-cause mortality was used as the primary endpoint and other outcomes of interest were used as secondary endpoints. The rates obtained were reported and contextualized. Results: The in-hospital rate of all-cause mortality was 1.0%, MACE was 3.1%. Severe hypotension occurred in 8.9% of patients. Major bleeding and major vascular complications occurred in 1.0% and 2.1%, respectively. Acute myocardial infarction occurred in 0.7% of patients. Cerebrovascular events occurred in 1.4% of patients. Cardiac arrest occurred in 1.7% of patients. A statistically significant improvement in blood pressure was observed with iVAC2L activation. Conclusions: The results of the present study suggest that the iVAC2L is capable of improving hemodynamics with a low rate of adverse events. However, confirmatory studies are needed to validate these findings. Full article

Cardiac amyloidosis is an infiltrative disease that causes progressive myocardial impairment secondary to amyloid fibril deposition in the extracellular space of the myocardium. Many amyloid precursors, including transthyretin protein, are known to determine cardiac damage by aggregating and precipitating in cardiac tissue. Transthyretin cardiac amyloidosis may be either caused by rare genetic mutations of the transthyretin gene in the hereditary variant, or may arise as a consequence of age-related mechanisms in the acquired form. Although it has been labeled as a rare disease, in recent years, transthyretin cardiac amyloidosis has stood out as an emerging cause of aortic stenosis, unexplained left ventricular hypertrophy and heart failure with preserved ejection fraction, particularly in the elderly. Indeed, the integration of data deriving from both in vivo imaging techniques (whose advancement in the last years has allowed to achieve an easier and more accessible non-invasive diagnosis) and forensic studies (showing a prevalence of amyloid deposition in cardiac tissue of elderly patients up to 29%) suggests that cardiac amyloidosis is a more common disease than traditionally considered. Thanks to all the improvements in non-invasive diagnostic techniques, along with the development of efficacious therapies offering improvements in survival rates, transthyretin cardiac amyloidosis has been transformed from an incurable and infrequent condition to a relatively more diffuse and treatable disease, which physicians should take into consideration in the differential diagnostic processes in daily clinical practice. Full article

Acute coronary syndrome (ACS) is a complex clinical syndrome that encompasses acute myocardial infarction (AMI) and unstable angina (UA). Its underlying mechanism refers to coronary plaque disruption, with consequent platelet aggregation and thrombosis. Inflammation plays an important role in the progression of atherosclerosis by mediating the removal of necrotic tissue following myocardial infarction and shaping the repair processes that are essential for the recovery process after ACS. As a chronic inflammatory disorder, atherosclerosis is characterized by dysfunctional immune inflammation involving interactions between immune (macrophages, T lymphocytes, and monocytes) and vascular cells (endothelial cells and smooth muscle cells). New-onset atrial fibrillation (NOAF) is one of the most common arrhythmic complications in the setting of acute coronary syndromes, especially in the early stages, when the myocardial inflammatory reaction is at its maximum. The main changes in the atrial substrate are due to atrial ischemia and acute infarcts that can be attributed to neurohormonal factors. The high incidence of atrial fibrillation (AF) post-myocardial infarction may be secondary to inflammation. Inflammatory response and immune system cells have been involved in the initiation and development of atrial fibrillation. Several inflammatory indexes, such as C-reactive protein and interleukins, have been demonstrated to be predictive of prognosis in patients with ACS. The cell signaling activation patterns associated with fibrosis, apoptosis, and hypertrophy are forms of cardiac remodeling that occur at the atrial level, predisposing to AF. According to a recent study, the presence of fibrosis and lymphomononuclear infiltration in the atrial tissue was associated with a prior history of AF. However, inflammation may contribute to both the occurrence/maintenance of AF and its thromboembolic complications. Full article

Cathelicidins (human LL-37 and rat CRAMP) are multifunctional peptides involved in various cardiovascular conditions. This review integrates the recent findings about the functional involvement of LL-37/CRAMP across atherosclerosis, acute coronary syndrome, myocardial infarction, heart failure, diabetic cardiomyopathy, and platelet aggregation/thrombosis. In atherosclerosis, LL-37 interacts with scavenger receptors to modulate lipid metabolism and binds with mitochondrial DNA and lipoproteins. In acute coronary syndrome, LL-37 influences T cell responses and mitigates calcification within atherosclerotic plaques. During myocardial infarction and ischaemia/reperfusion injury, LL-37/CRAMP exhibits dual roles: protecting against myocardial damage through the AKT and ERK1/2 signalling pathways, while exacerbating inflammation via TLR4 and NLRP3 inflammasome activation. In heart failure, LL-37/CRAMP attenuates hypertrophy and fibrosis via NF-κB inhibition and the activation of the IGFR1/PI3K/AKT and TLR9/AMPK pathways. Moreover, in diabetic cardiomyopathy, these peptides alleviate oxidative stress and fibrosis by inhibiting TGFβ/Smad and AMPK/mTOR signalling and provide anti-inflammatory effects by reducing NF-κB nuclear translocation and NLRP3 inflammasome formation. LL-37/CRAMP also modulates platelet aggregation and thrombosis through the FPR2 and GPVI receptors, impacting apoptosis, autophagy, and other critical cellular processes. This comprehensive overview underscores LL-37/CRAMP as a promising therapeutic target in cardiovascular diseases, necessitating further elucidation of its intricate signalling networks and biological effects for clinical translation. Full article

Acute hyperglycemia is a transient increase in plasma glucose level (PGL) frequently observed in patients with ST-elevation myocardial infarction (STEMI). The aim of this review is to clarify the molecular mechanisms whereby acute hyperglycemia impacts coronary flow and myocardial perfusion in patients with acute myocardial infarction (AMI) and to discuss the consequent clinical and prognostic implications. We conducted a comprehensive literature review on the molecular causes of myocardial damage driven by acute hyperglycemia in the context of AMI. The negative impact of high PGL on admission recognizes a multifactorial etiology involving endothelial function, oxidative stress, production of leukocyte adhesion molecules, platelet aggregation, and activation of the coagulation cascade. The current evidence suggests that all these pathophysiological mechanisms compromise myocardial perfusion as a whole and not only in the culprit coronary artery. Acute hyperglycemia on admission, regardless of whether or not in the context of a diabetes mellitus history, could be, thus, identified as a predictor of worse myocardial reperfusion and poorer prognosis in patients with AMI. In order to reduce hyperglycemia-related complications, it seems rational to pursue in these patients an adequate and quick control of PGL, despite the best pharmacological treatment for acute hyperglycemia still remaining a matter of debate. Full article