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AF diagnosis. Clinical Trial Registration ClinicalTrials.gov, identifier [NCT03197090].Atherosclerosis is a complex pathology that involves both metabolic dysfunction and chronic inflammatory process. During the last decade, a considerable progress was achieved in describing the pathophysiological features of atherosclerosis and developing approaches that target the abnormal lipid metabolism and chronic inflammation. However, early events in the arterial wall that initiate the disease development still remain obscure. Finding effective therapeutic targets in these early processes would allow developing methods for disease prevention and, possibly, atherosclerotic plaque regression. Currently, these early events are being actively studied by several research groups. One of the processes that are being investigated is the development of mitochondrial dysfunction, which was demonstrated to be present in the affected areas of the arterial wall. Detection and characterization of mitochondrial dysfunction associated with several chronic human disorders was made possible by the improved methods of studying mitochondrial biology and detecting mitochondrial DNA (mtDNA) mutations. It was found to be involved in several key atherogenic processes, such as oxidative stress, chronic inflammation, and intracellular lipid accumulation. Mitochondrial dysfunction can occur in all types of cells involved in the pathogenesis of atherosclerosis monocytes and macrophages, smooth muscle cells, lymphocytes, and the endothelial cells. However, therapies that would specifically target the mitochondria to correct mitochondrial dysfunction and neutralize the defective organelles are still remain to be developed and characterized. The aim of this review is to outline the prospects for mitochondrial therapy for atherosclerosis. We discuss mechanisms of mitochondria-mediated atherogenic processes, known mitochondria-targeting therapy strategies, and novel mitochondria-targeting drugs in the context of atherosclerosis.This study aimed to investigate the effects of pulse pressure (PP) on cognition and the role of white matter lesions (WMLs) in mediating this association. We enrolled 3,009 participants from the SPRINT-MIND study. Of those, 755 participants underwent brain magnetic resonance imaging. Cognitive tests were summarized in five cognition domains, including global cognition, executive function, attention, memory, and language. Multiple linear regression models were employed to analyze PP in association with cognition, and mediation analysis was applied to determine the role of WMLs in the association between PP and cognition. We found that PP was negatively linearly associated with global cognition (β = -0.048, P = 0.008), executive function (β = -0.014, P = 0.040), attention (β = -0.013, P = 0.035), memory (β = -0.021, P = 0.045), and language (β = -0.020, P = 0.001), respectively. Furthermore, PP was not significantly associated with brain component volume changes, except for WMLs (β = 0.029, P = 0.044). Additionally, mediation analysis showed that increased WML volume contributed to 10.8% of global cognition, 9.5% of executive function, 10.6% of memory, and 7.2% of language decline associated with PP. Exposure to higher PP levels was associated with poor cognitive performance, and WMLs partially moderated the influence of PP on cognition.Coronary artery disease (CAD) is present in 40-75% of patients undergoing transcatheter aortic valve implantation (TAVI) for severe symptomatic aortic stenosis. Currently, the indication for TAVI is expanding toward younger patients at lower surgical risk. Given the progressive nature of CAD, the necessity for coronary angiography (CA), including percutaneous coronary intervention (PCI), will subsequently increase as in the future TAVI patients will be younger and have a longer life expectancy. Data on the impact of PCI in patients with severe CAD scheduled for TAVI are controversial, and although European and US guidelines recommend PCI before TAVI, the optimal timing for PCI remains unclear due to a lack of evidence. Depending on the valve type, position, and axial alignment of the implanted device, CA and/or PCI after TAVI can be challenging. Hence, every interventionalist should be familiar with the different types of transcatheter heart valves and their characteristics and technical issues that can arise during invasive coronary procedures. click here This review provides an overview of current data regarding the prevalence and clinical implications of CAD and PCI in TAVI patients and includes useful guidance for practical management in the clinical routine.Background In the absence of SARS-CoV-2 specific antiviral treatments, various repurposed pharmaceutical approaches are under investigation for the treatment of COVID-19. Antiviral drugs considered for this condition include atazanavir, remdesivir, lopinavir-ritonavir, and favipiravir. Whilst the combination of lopinavir and ritonavir has been previously linked to prolongation of the QTc interval on the ECG and risk of torsades de pointes arrhythmia, less is known in this regard about atazanavir, remdesivir, and favipiravir. Unwanted abnormalities of drug-induced QTc prolongation by diverse drugs are commonly mediated by a single cardiac anti-target, the hERG potassium channel. This computational modeling study was undertaken in order to explore the ability of these five drugs to interact with known determinants of drug binding to the hERG channel pore. Methods Atazanavir, remdesivir, ritonavir, lopinavir and favipiravir were docked to in silico models of the pore domain of hERG, derived from cryo-EM structurl. Conclusions All the antiviral drugs studied here can, in principle, interact with components of the hERG potassium channel canonical binding site, but are likely to differ in their ability to access lateral binding pockets. Favipiravir's small size and relatively paucity of simultaneous interactions may confer reduced hERG liability compared to the other drugs. Experimental structure-function studies are now warranted to validate these observations.Objective Besides hyperlipidemia, inflammation is an important determinant in the initiation and the progression of atherosclerosis. As Neuroimmune Guidance Cues (NGCs) are emerging as regulators of atherosclerosis, we set out to investigate the expression and function of inflammation-regulated NGCs. Methods and results NGC expression in human monocytes and endothelial cells was assessed using a publicly available RNA dataset. Next, the mRNA levels of expressed NGCs were analyzed in primary human monocytes and endothelial cells after stimulation with IL1β or TNFα. Upon stimulation a total of 14 and 19 NGCs in monocytes and endothelial cells, respectively, were differentially expressed. Since plexin A4 (PLXNA4) was strongly downregulated in endothelial cells under inflammatory conditions, the role of PLXNA4 in endothelial function was investigated. Knockdown of PLXNA4 in endothelial cells markedly impaired the integrity of the monolayer leading to more elongated cells with an inflammatory phenotype. In addition, these cells showed an increase in actin stress fibers and decreased cell-cell junctions.