Current vascular pharmacology最新文献

Aim: This study aimed to evaluate clinical outcomes, including recurrent acute coronary syndrome (ACS) and mortality, in ACS patients with varying HbA1c levels, addressing the controversy over optimal targets in those with newly diagnosed and pre-existing diabetes mellitus (DM).

Methods: From January 2005 to December 2019, a total of 33,990 patients were identified with ACS in the Chang Gung Research Database based on their medical history. After excluding patients without DM and baseline or subsequent HbA1C data, a cohort of 11,870 DM patients was divided into two groups: one consisting of 6,089 patients with newly diagnosed DM and the other comprising 5,781 patients with pre-existing DM.

Results: During the three-year follow-up, the pre-existing DM group experienced worse clinical outcomes, such as increased rates of re-ACS, major bleeding, cardiovascular (CV) events, and all-cause mortality. Optimal HbA1c levels for mitigating re-ACS and/or CV mortality and all-cause mortality appeared to differ between the two DM cohorts. Re-ACS and CV mortality reached their highest at an HbA1c of 6.8% for all DM patients, 6.6% for newly diagnosed, and 6.7% for pre-existing cases. The greatest all-cause mortality risk was at an HbA1c of 7.4% for all DM patients, 7.0% in newly diagnosed, and 8.2% in pre-existing patients.

Conclusion: Upon comparing newly diagnosed DM patients with those with pre-existing DM, a poorer prognosis was observed in the latter group, attributed to older age and a higher burden of comorbidities. Throughout the follow-up period, maintaining consistently low HbA1c levels did not reduce the incidence of re-ACS nor enhance survival rates.

Pericytes, also known as mural cells, are cells embedded between endothelial cells and the basement membrane of capillaries, where they orchestrate the morphological and functional homeostasis of blood vessels. Within the tumor microenvironment, pericytes interact closely with various cellular components, including tumor cells, stromal cells, and immune cells. Through these dynamic interactions, pericytes are activated and subsequently transform into tumor-associated pericytes (TPCs). The origin of TPCs varies depending on the tissue and tumor type, contributing to their phenotypic and functional heterogeneity. TPCs play pivotal roles in facilitating tumor progression, metastasis, immune evasion, and therapeutic resistance by promoting angiogenesis, engaging in reciprocal interactions with tumor cells, remodeling the extracellular matrix, and fostering an immunosuppressive microenvironment. This review synthesizes the latest significant advancements in targeted therapies against TPCs. It underscores the challenges inherent in developing effective anti-TPC therapies, which include the heterogeneity and pluripotency of TPCs, the absence of specific markers for precise TPC targeting, and the limited understanding of how current anti-tumor therapies affect TPCs and vice versa. This review furnishes a comprehensive understanding of the origins, markers, and functions of TPCs, and their interplays within the tumor microenvironment, providing prospective strategies for more effective anti-tumor therapy.

Cardioimmunology is an emerging branch of medicine whose development has been facilitated by more sophisticated diagnostic procedures. Recent studies have mainly focused on the immune response during myocardial infarction (MI), and there is evidence that both resident and external immune cells participate in acute inflammatory disease, as well as tissue remodeling. Following MI, macrophages, dendritic cells (DCs) and mast cells (MCs) are the main players in the heart. Under steady-state conditions, cardiac resident macrophages (CRMs) protect the heart against stress and infectious events, being involved in cell and matrix turnover, as well as phagocytosis of apoptotic cells. Moreover, CRMs contribute to the resolution of inflammation via release of interleukin (IL)-10, and efferocytosis of dying cells. Conversely, CCR2+ monocytederived macrophages promote inflammation in the acute phase of myocardial damage, with the release of pro-inflammatory cytokines. Conventional (c) DCs possess enhanced capacity to present antigens to T lymphocytes. In MI patient autopsies, massive infiltration of T helper (Th) cells and CDs has been detected in the myocardium. Cardiac MCs play a dual role during MI, with the production of cytokines for early inflammatory response, and the release of anti-inflammatory cytokines, IL10 and IL-13 during the resolution phase. In experimental coronary artery ligation, the myocardium is infiltrated with Th1, Th2, Th17, and T regulatory (TREG) cells, which participate in the acute inflammation. In cardiac repair, T cell reparative response is mediated by TREG cells, with improved ventricular remodeling and function post-ischemia. In this review, emphasis will be placed on the innate and adaptive immune response during and post-MI. At the same time, immunotherapy- based cardiac failure following chimeric antigen receptor T-cell and immune checkpoint inhibitory therapy will be pointed out.

Introduction: Current guidelines and consensus statements advise caution in using direct oral anticoagulants (DOACs) for morbidly obese patients with body mass index (BMI) >40 kg/m2, indicating warfarin as the most studied treatment.

Methods: We systematically searched databases from their inception to January 4, 2024, to identify studies that evaluated the effectiveness and safety of DOACs compared to warfarin in patients with BMI >40 kg/m² and atrial fibrillation (AF) or venous thromboembolism (VTE). The outcomes of allcause mortality, major and minor bleeding, stroke/systematic embolism (SE), VTE, and their composite endpoint were analyzed using a random-effects model.

Results: This meta-analysis included 24 studies and 119,960 morbidly obese patients with AF or VTE on oral anticoagulation therapy: 51,363 on DOACs (43%) vs. (57%) 68,597 on warfarin. DOAC use was significantly associated with lower all-cause mortality and major bleeding risk compared to warfarin. Although the risk of composite endpoint, stroke/SE, and VTE was lower in the DOAC group, no statistically significant difference was observed, indicating no superiority of warfarin compared to DOAC use. The risk of minor bleeding events, hemorrhagic stroke, and ischemic stroke was lower in the DOAC compared to the warfarin group. The same trend favoring DOACs over warfarin in all assessed endpoints was observed in the subgroup analysis based on anticoagulation indication (AF or VTE).

Conclusion: Our findings have documented a potentially more effective and safer profile of DOACs compared to warfarin in morbidly obese patients regardless of the indication for anticoagulation.

Introduction/objective: Atrial fibrillation (AF) could present with slow ventricular-response; bradycardia could facilitate the emergence of AF. The conviction that one "does not succumb" from bradycardia as an escape rhythm will emerge unless one sustains a fatal injury following syncope is in stark difference with ventricular tachyarrhythmia (VA), which may promptly cause cardiac arrest. However, this is not always the case, as a life-threatening situation may emerge during the bradycardic episode, i.e., the development of bradycardia-induced VAs, which could be fatal if there is no prompt intervention.

Methods: An extensive review of the literature was undertaken with key words including but not limited to AF, bradycardia, bradyarrhythmia, AF and bradycardia, slow ventricular response, sinus node dysfunction, sick sinus syndrome, tachycardia-bradycardia syndrome.

Results: AF is the commonest cardia arrhythmia worldwide and may be part of sick sinus syndrome, commonly presenting as bradycardia-tachycardia syndrome. Importantly, bradycardia-related cardiomyopathy and heart failure, as well as an adverse influence on brain function, may all be eluding consequences of this type of syndrome. Bradycardia could be the inciting mechanism for the occurrence of AF, and when the bradycardia is eliminated, AF may not recur. The bradycardia-related long-short-long sequence triggering VAs can be averted by pacing at rates ~80-110 bpm either via temporary or permanent pacing as needed.

Conclusion: Balancing the benefits and risks of bradycardia together with other risks of antiarrhythmic drug and/or pacing management of AF versus those of catheter ablation is indeed a vexing problem; all these issues are herein discussed, tabulated, and pictorially illustrated.

Cardiovascular disorders (CVDs) are reported to occur with very high rates of incidence and exhibit high morbidity and mortality rates across the globe. Therefore, research is focused on searching for novel therapeutic targets involving multiple pathophysiological mechanisms. Oxidative stress plays a critical role in the development and progression of various CVDs, such as hypertension, pulmonary hypertension, heart failure, arrhythmia, atherosclerosis, ischemia- reperfusion injury, and myocardial infarction. Among multiple pathways generating reactive oxygen species (ROS), Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases of the NOX family as the major source of ROS generation and plays an intricate role in the development and progression of CVDs. Therefore, exploring the role of different NADPH oxidase isoforms in various cardiovascular pathologies has attracted attention to current cardiovascular research. Focusing on NADPH oxidases to reduce oxidative stress in managing diverse CVDs may offer unique therapeutic approaches to prevent and treat various heart conditions. The current review article highlights the role of different NADPH oxidase isoforms in the pathophysiology of various CVDs. Moreover, the focus is also to emphasize different experimental studies that utilized various NADPH oxidase isoform modulators to manage other disorders. The present review article considers new avenues for researchers/scientists working in the field of cardiovascular pharmacology utilizing NADPH oxidase isoform modulators.

Abdominal Aortic Aneurysm (AAA) is a life-threatening vascular disease. Despite advancements in understanding the pathogenesis of AAA, significant knowledge gaps persist. Recent evidence increasingly implicates mitochondrial dysfunction as a contributing factor that exacerbates AAA, inducing further expansion of aneurysm, rupture, and subsequent death. This review summarizes the latest research findings and theories associated with AAA pathogenesis, with a particular focus on mitochondrial dysfunction in AAA, including mitochondrial quality control, mitochondrial membrane potential, mitochondrial morphology, oxidation and antioxidation, normal functioning of the respiratory chain, mitochondrial mutations, and the regulation of other mitochondrial signaling pathways. Moreover, we highlight potential medical interventions based on regulating mitochondrial function for AAA treatment.

Introduction: Sodium Glucose cotransporter-2 inhibitors (SGLT2is) possess pleiotropic effects, such as antioxidant, antifibrotic, anti-inflammatory, and vascular remodeling activities. Considering the lack of literature, a network meta-analysis was conducted to explore the impact of SGLT2is on endothelial dysfunction and arterial stiffness in the diabetic population.

Methods: Electronic databases were searched to identify randomized clinical trials evaluating the effects of SGLT2is on outcomes, such as Flow-mediated Vasodilation (FMV), Pulse Wave Velocity (PWV), and Augmentation Index (AIx). Direct, indirect, and mixed treatment comparisons generated pooled estimates using random-effects modeling. Effect sizes were reported as Hedges' g with 95% Confidence Interval (95% CI). Bootstrap and permutation meta-analyses were performed using ranking plots. The certainty of evidence was graded.

Results: Twelve articles (706 participants) were included. SGLT2is were associated with significant improvements in FMV (g: 0.48; 95% CI: 0.08, 0.88), confirmed by bootstrap meta-analysis (g: 0.48; 95% CI: 0.1, 0.85) and permutation meta-analysis of FMV (g: 0.48; 95% CI: 0.05, 0.9). Within SGLT2is, dapagliflozin (g: 0.39; 95% CI: 0.14, 0.65) significantly improved FMV, and dapagliflozin (g: -0.61, 95% CI: -0.98, -0.24) and tofogliflozin (g: -3.51; 95% CI: -4.05, -2.98) significantly improved PWV. A low risk of publication bias was observed, and the ranking plots revealed dapagliflozin to have the best probability (0.99) of being the most effective for improving FMV. Low certainty of evidence was observed for all outcomes.

Conclusion: SGLT2 inhibitors improve endothelial function and arterial stiffness in the diabetic population. Clinical studies evaluating the association between improvements in endothelial function with SGLT2is and reduced adverse cardiovascular and cardiorenal events and mortality are urgently needed.

Introduction: The global COVID-19 vaccination campaign has significantly reduced severe illness and mortality; however, emerging evidence raises concerns regarding its potential cardiovascular effects, particularly myocardial infarction (MI).

Methods: This study investigates the relationship between COVID-19 vaccination and MI incidence among first-time MI patients in Saudi Arabia. Post-COVID-19 vaccination within six months postvaccination accounted for potential confounding factors, such as pre-existing health conditions, age, and lifestyle. A total of 102 MI patients, with a male predominance of 60.8% and a significant correlation with middle age, were analysed. A+ blood group patients were the most prevalent (33.3%), followed by B+ (29.4%), while Rh-negative patients constituted only 7.8%. Elevated mean BNP (761.98 pg/ml), pulse rate (87.72 bpm), and systolic blood pressure (139.98 mmHg) indicated heightened cardiac stress (p < 0.01).

Results: Significant elevations in AST (121.65 U/L) and ALT (133.63 U/L) levels suggested liver stress post-Covid-19 vaccination (p < 0.01). Males had higher AST, ALT, and bilirubin levels than females, with p-values of 0.02, 0.01, and 0.04, respectively, indicating hepatic differences. Elevated biomarkers like CK-MB (58.05 IU/L) and CPK (313.86 mcg/L) further affirmed significant myocardial damage post-vaccination (p < 0.05).

Conclusion: These findings suggest a link between vaccination and cardiovascular events and highlight the importance of considering individual health profiles in evaluating vaccine safety, cardiovascular health, and hepatic implications.

Introduction: With the widespread use of the radial artery in catheterization procedures, radial artery spasm (RAS) is frequently considered an undesirable event. It is known that anxiety increases RAS, and listening to music helps individuals control anxiety during the procedure. This study aimed to investigate the effects of music concerts on RAS.

Methods: In this prospective study, imaging and interventional coronary catheterization procedures using the radial artery were included. One group listened to a musical recital during the procedure, while the other group was treated in a quiet environment. The demographics, procedural parameters, and complications of both groups were compared.

Results: The study included a total of 147 patients, with an average age of 51.6 ± 11.1 years. Of these, 78 patients (53%) listened to music, while 69 patients (46.9%) underwent catheterization in a quiet environment. The impact of music therapy on the RAS was found to be significant (11.5% vs. 20.3%; p=0.035). While music therapy showed a potential to reduce RAS rates, its effect was not statistically significant in multivariate analysis (p=0.055).

Conclusion: Music is a feasible, simple, and inexpensive method for reducing anxiety levels in patients. Listening to music during catheterization can reduce procedural discomfort and the frequency of undesirable events by helping people control their anxiety.