Calcific aortic valve disease (CAVD) is a major cause of cardiovascular mortality and morbidity, with increased prevalence and incidence. The underlying mechanisms behind CAVD are complex, and are mainly illustrated by inflammation, mechanical stress (which induces prolonged aortic valve endothelial dysfunction), increased oxidative stress (OS) (which trigger fibrosis), and calcification of valve leaflets. To date, besides aortic valve replacement, there are no specific pharmacological treatments for CAVD. In this review, we describe the mechanisms behind aortic valvular disease, the involvement of OS as a fundamental element in disease progression with predilection in AS, and its two most frequent etiologies (calcific aortic valve disease and bicuspid aortic valve); moreover, we highlight the potential of OS as a future therapeutic target.

Brugada syndrome (BrS) is a rare hereditary arrhythmia disorder, with a distinctive ECG pattern, correlated with an increased risk of ventricular arrhythmias and sudden cardiac death (SCD) in young adults. BrS is a complex entity in terms of mechanisms, genetics, diagnosis, arrhythmia risk stratification, and management. The main electrophysiological mechanism of BrS requires further research, with prevailing theories centered on aberrant repolarization, depolarization, and current-load match. Computational modelling, pre-clinical, and clinical research show that BrS molecular anomalies result in excitation wavelength (k) modifications, which eventually increase the risk of arrhythmia. Although a mutation in the SCN5A (Sodium Voltage-Gated Channel Alpha Subunit 5) gene was first reported almost two decades ago, BrS is still currently regarded as a Mendelian condition inherited in an autosomal dominant manner with incomplete penetrance, despite the recent developments in the field of genetics and the latest hypothesis of additional inheritance pathways proposing a more complex mode of inheritance. In spite of the extensive use of the next-generation sequencing (NGS) technique with high coverage, genetics remains unexplained in a number of clinically confirmed cases. Except for the SCN5A which encodes the cardiac sodium channel NaV1.5, susceptibility genes remain mostly unidentified. The predominance of cardiac transcription factor loci suggests that transcriptional regulation is essential to the Brugada syndrome’s pathogenesis. It appears that BrS is a multifactorial disease, which is influenced by several loci, each of which is affected by the environment. The primary challenge in individuals with a BrS type 1 ECG is to identify those who are at risk for sudden death, researchers propose the use of a multiparametric clinical and instrumental strategy for risk stratification. The aim of this review is to summarize the latest findings addressing the genetic architecture of BrS and to provide novel perspectives into its molecular underpinnings and novel models of risk stratification.

The endocannabinoid system (ECS) dynamically regulates many aspects of mammalian physiology. ECS has gained substantial interest since growing evidence suggests that it also plays a major role in several pathophysiological conditions due to its ability to modulate various underlying mechanisms. Furthermore, cannabinoids, as components of the cannabinoid system (CS), have proven beneficial effects such as anti-inflammatory, immunomodulatory, neuromodulatory, antioxidative, and cardioprotective effects. In this comprehensive review, we aimed to describe the complex interaction between CS and most common age-related diseases such as neuro-degenerative, oncological, skeletal, and cardiovascular disorders, together with the potential of various cannabinoids to ameliorate the progression of these disorders. Since chronic inflammation is postulated as the pillar of all the above-mentioned medical conditions, we also discuss in this paper the potential of CS to ameliorate aging-associated immune system dysregulation.

Arterial hypertension (HTN) is one of the most prevalent entities globally, characterized by increased incidence and heterogeneous pathophysiology. Among possible etiologies, oxidative stress (OS) is currently extensively studied, with emerging evidence showing its involvement in endothelial dysfunction and in different cardiovascular diseases (CVD) such as HTN, as well as its potential as a therapeutic target. While there is a clear physiological equilibrium between reactive oxygen species (ROS) and antioxidants essential for many cellular functions, excessive levels of ROS lead to vascular cell impairment with decreased nitric oxide (NO) availability and vasoconstriction, which promotes HTN. On the other hand, transcription factors such as nuclear factor erythroid factor 2-related factor 2 (Nrf2) mediate antioxidant response pathways and maintain cellular reduction–oxidation homeostasis, exerting protective effects. In this review, we describe the relationship between OS and hypertension-induced endothelial dysfunction and the involvement and therapeutic potential of Nrf2 in HTN.

Background: Acute pulmonary embolism (PE) is a condition with increased morbidity and mortality. It is important to identify patients with high mortality risk. Inflammation and thrombosis are interconnected in the pathophysiology of PE. The aim of the study was to investigate the prognostic value of multiple blood cellular indices such as neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte platelet ratio (NLPR), systemic immune–inflammation index (SII), systemic inflammation response index (SIRI) and aggregate index of systemic inflammation (AISI) in acute PE. Methods: A total of 157 patients with acute PE confirmed by chest computed tomographic angiography (CTPA) were enrolled. These patients were divided into two categories according to the simplified pulmonary embolism severity index (sPESI): high risk and low risk. Results: Univariate logistic regression analysis showed that right ventricle dysfunction, NLR, SII and SIRI were significantly associated with high risk of acute PE. NLR of 4.32 was associated with high-risk PE with a sensitivity of 57.4% and specificity of 65.7% (AUC = 0.635). SII of 1086.55 was associated with high-risk PE with a sensitivity of 55.7% and specificity of 71.4% (AUC = 0.614). SIRI of 2.87 was associated with high-risk PE with a sensitivity of 59% and specificity of 62.9% (AUC = 0.624). Multivariate logistic regression analysis demonstrated that right ventricle dysfunction, NLR, PLR and NLPR are independent predictors of high-risk acute PE. Secondly, NLR, NLPR, SII and SIRI were significantly correlated with in-hospital mortality of acute PE. Based on receiver-operating characteristic (ROC) curve values of 7.66 for NLR (AUC 0.911, sensitivity of 85.7% and sensibility of 83%), 0.02 for NLPR (AUC 0.871, sensitivity of 85.7% and sensibility of 70%), 1542.71 for SII (AUC 0.782, sensitivity of 71.4% and sensibility of 72%) and 5.72 for SIRI (AUC 0.788, sensitivity of 71.4% and sensibility of 73%) could predict in-hospital mortality. Conclusions: The blood cellular indices (NLR, NLPR, SII and SIRI) are associated with high-risk acute PE and in-hospital mortality. Right ventricular dysfunction, NLR and NLPR are independent predictors for high-risk acute PE.