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Highlights • Activated platelets are associated with AS. • Platelets are a player in bioprosthetic valve dysfunction. • Randomized trials have assessed clinical outcomes with various antiplatelet/anticoagulation strategies in patients undergoing TAVR., Summary Aortic stenosis (AS) is the most common heart valve disease requiring surgery in developed countries, with a rising global burden associated with aging populations. The predominant cause of AS is believed to be driven by calcific degeneration of the aortic valve and a growing body of evidence suggests that platelets play a major role in this disease pathophysiology. Furthermore, platelets are a player in bioprosthetic valve dysfunction caused by their role in leaflet thrombosis and thickening. This review presents the molecular function of platelets in the context of recent and rapidly evolving understanding the role of platelets in AS, both of the native aortic valve and bioprosthetic valves, where there remain concerns about the effects of subclinical leaflet thrombosis on long-term prosthesis durability. This review also presents the role of antiplatelet and anticoagulation therapies on modulating the impact of platelets on native and bioprosthetic aortic valves, highlighting the need for further studies to determine whether these therapies are protective and may increase the life span of surgical and transcatheter aortic valve implants. By linking molecular mechanisms through which platelets drive disease of native and bioprosthetic aortic valves with studies evaluating the clinical impact of antiplatelet and antithrombotic therapies, we aim to bridge the gaps between our basic science understanding of platelet biology and their role in patients with AS and ensuing preventive and therapeutic implications., Central Illustration

Hemodialysis vascular access dysfunction is a common and intractable problem in clinical practice with no definitive therapy yet available. As a key mediator of vascular and cardiac maladaptive remodeling, mineralocorticoid receptor (MR) plays a pivotal role in vascular fibrosis and intimal hyperplasia (IH) and is potentiated locally in hemodialysis vascular access following diverse injuries, like barotrauma, cannulation and shear stress. MR-related genomic and non-genomic pathways are responsible for triggering vascular smooth muscle cell activation, proliferation, migration and extracellular matrix overproduction. In endothelial cells, MR signaling diminishes nitric oxide production and its bioavailability, but amplifies reactive oxygen species, leading to an inflammatory state. Moreover, MR favors macrophage polarization towards a pro-inflammatory phenotype. In clinical settings like post-angioplasty or stenting restenosis, the beneficial effect of MR antagonists on vascular fibrosis and IH has been validated. In aggregate, therapeutic targeting of MR may provide a new avenue to prevent hemodialysis vascular access dysfunction., Highlights • MR signaling is instrumental in both insufficient outward remodeling and exuberant inward remodeling of AVF. • The effects of MR in VSMC, endothelial cell, and macrophage act synergistically to promote IH and vascular fibrosis in AVF. • Pharmacological targeting of MR represents a novel therapeutic strategy to prevent hemodialysis vascular access dysfunction.

Background Intraoperative rupture is the most fatal and catastrophic complication of surgery for unruptured intracranial aneurysms (UIAs); thus, it is extremely useful to predict reddish and thin-walled regions of the UIA before surgery. Although several studies have reported a relationship between the hemodynamic characteristics and intracranial aneurysm wall thickness, a consistent opinion is lacking. We aimed to investigate the relationship between objectively and quantitatively evaluated bleb wall color and hemodynamic characteristics using phase-contrast magnetic resonance angiography (PC-MRA). Methods Ten patients diagnosed with UIA who underwent surgical clipping and preoperative magnetic resonance imaging along with PC-MRA were included in this study. Bleb wall color was evaluated from an intraoperative video. Based on the Red (R), Green, and Blue values, bleb wall redness (modified R value; mR) was calculated and compared with the hemodynamic characteristics obtained from PC-MRA. Results The wall redness distribution of 18 blebs in 11 UIAs in 10 patients was analyzed. Bleb/neck inflow velocity ratio (Vb/Va: r = 0.66, P = 0.003) strongly correlated with mR, whereas bleb/neck inflow rate ratio (r = 0.58, P = 0.012) correlated moderately. Multivariate regression analysis revealed that only Vb/Va (P = 0.017) significantly correlated with mR. There was no correlation between wall shear stress and mR. Conclusions The bleb redness of UIAs and Vb/Va, calculated using PC-MRA, showed a significantly greater correlation. Thus, it is possible to predict bleb thickness noninvasively before surgery. This will facilitate more detailed pre- and intraoperative strategies for clipping and coiling for safe surgery.