Current vascular pharmacology最新文献

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), NADPH defines all abbreviations 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.

Atrial fibrillation (AF) is the commonest cardiac arrhythmia, constituting a major cause of morbidity and mortality, with an age-dependent incidence and prevalence ranging from 1-2% in the general population to ~10% in persons aged >60 years. The global prevalence of AF is rapidly increasing, mostly due to the aging population. If not properly and timely managed, this arrhythmia adversely affects left ventricular function, increases the risk of stroke five-fold, impairs quality of life, and shortens longevity. There is a genetic, hence non-modifiable, predisposition to the arrhythmia, while several life-style and cardiometabolic inciting factors, such as hypertension, heart failure, coronary disease, metabolic syndrome, alcohol use, and thyroid disorders, can be addressed, attesting to the importance of a holistic approach to its management. Thromboembolism is a serious consequence of AF, which could lead to a disabling stroke or have a lethal outcome. The risk of a thromboembolic complication can be estimated as based on a scoring system that takes into consideration the patient's age, previous thromboembolic events, and clinical comorbidities. In addition, rapid AF could affect cardiac performance, leading to an elusive type of arrhythmia-induced cardiomyopathy and heart failure with grave consequences if undetected and untreated. Furthermore, AF may cause silent brain infarcts and/or its hemodynamic perturbations can account for a type of dementia that needs to be taken into account, emphasizing the need for AF screening and prevention strategies. All these issues are herein detailed, the causes of the arrhythmia are tabulated, and an algorithm illustrates our current approach to its management.

Background: Postoperative atrial fibrillation (POAF) is associated with poor outcomes, including hemodynamic instability, stroke, myocardial infarction, and death. In hemodynamic stable patients, the rhythm-control strategy is more advantageous than rate control. Current standard intravenous amiodarone administration has limited success and a delayed effect; the acute success rate is 44% (8-12 h to several days).

Purpose: The aim of this study was to evaluate the effectiveness of higher amiodarone loading dosage to restore sinus rhythm in patients with POAF after noncardiac surgery.

Methods: This is a prospective, randomized, controlled single-center study. The study included 39 patients with POAF, divided into group I (n=27) (intravenous 600 mg amiodarone loading dosage over 2 h and infusion of 50 mg/h over a 24-h period) and group II (n=12) (standard protocol; 300 mg of bolus intravenously in 30 min and infusion of 50 mg/h over a 24-h period). The primary endpoint of the study was a restoration of sinus rhythm at the 24th hour.

Results: Baseline clinical, laboratory and echocardiographic characteristics of both groups were similar. The patients with higher loading amiodarone dosage had earlier restoration of sinus rhythm (2.38±1.41 vs 8.66±2.87 h, respectively; p=0.015). There was no significant difference in achieving sinus rhythm at the 24th hour between both groups.

Conclusion: Higher loading amiodarone dosage increased early conversions to sinus rhythm compared with standard amiodarone protocol in patients with POAF.

Background: Myocardial metabolism is closely related to functional changes after myocardial infarction (MI).

Objective: This study aimed to present an integrative examination of human ischemic cardiomyopathy.

Methods: We used both GSE121893 single-cell suspension sequencing and GSE19303 transcription microarray data sets from the GEO database, along with a murine MI model for full-spectrum metabolite detection. Through a systematic investigation that involved differential metabolite identification and functional enrichment analysis, we shed light on the pivotal role of energy metabolism dysregulation in the progression of MI.

Results: Our findings revealed an association between the core regulatory genes CDKN1A, FOS, ITGB4, and MAP2K1 and the underlying pathophysiology of the disease. These genes are identified as critical elements in the complex landscape of myocardial ischemic disorder, highlighting novel insights into therapeutic targets and the intricate biological mechanisms involved.

Conclusion: This analysis provides a framework for future research on the metabolic alterations associated with MI.

Background: Pulse Wave Velocity (PWV) remains the gold-standard method to assess Early Vascular Aging (EVA) defined by arterial stiffness. However, its high cost, time-consuming process, and need for qualified medical staff shows the importance of identifying alternative methods for the EVA evaluation.

Objective: In order to simplify the process of assessing patients' EVA, we recently developed the Early Vascular Aging Ambulatory score (EVAAs), a simple tool to predict the risk of EVA. The aim of the present study was the external validation of EVAAs in an independent population.

Methods: Eight hundred seventy-nine (46.3% men) patients who were referred to our Hypertension ESH Excellence Center were included in this study. The mean age was 46.43 ± 22.87 years. EVA was evaluated in two different ways. The first assessment included c-f PWV values, whereas the second one included EVAAs without the direct measurement of carotid-femoral PWV.

Results: The null hypothesis was that the prediction of EVA based on EVAAs does not present any statistically significant difference compared to the prediction based on the calculation from c-f PWV. Mean squared error (MSE) was used for the assessment of the null hypothesis, which was found to be 0.40. The results revealed that the EVAAs show the probability of EVA with 0.98 sensitivity and 0.75 specificity. The EVAAs present 95% positive predictive value and 92% negative predictive value.

Conclusion: Our study revealed that EVAAs could be as reliable as the carotid-femoral PWV to identify patients with EVA. Hence, we hope that EVAAs will be a useful tool in clinical practice.