Calcific Aortic Valve Disease (CAVD) is prevalent among the elderly as the most common valvular heart disease. Currently, no pharmaceutical interventions can effectively reverse or prevent CAVD, making valve replacement the primary therapeutic recourse. Extensive research spanning decades has contributed to the establishment of animal and in vitro cell models, which facilitates a deeper understanding of the pathophysiological progression and underlying mechanisms of CAVD. In this review, we provide a comprehensive summary and analysis of the strengths and limitations associated with commonly employed models for the study of valve calcification. We specifically emphasize the advancements in three-dimensional culture technologies, which replicate the structural complexity of the valve. Furthermore, we delve into prospective recommendations for advancing in vivo and in vitro model studies of CAVD.

Piezo1 plays a key role in the immune response during sepsis. To date, our understanding of the role of Piezo1 in inflammatory diseases has mostly been limited to influencing vasomotor function and regulating inflammatory infiltration. Whether and how Piezo1 in macrophages is involved in developing septic cardiac dysfunction has never been explored. Here, we have successfully established a mouse model with myeloid cell-specific knockdown of Piezo1. The intraperitoneal injection of lipopolysaccharide (LPS) resulted in a significant increase in cardiac macrophage infiltration, as well as an increase in the expression of inflammatory factors and the inflammatory response. However, myeloid cell-specific knockdown of Piezo1 impaired this response, leading to an increase in macrophage polarization towards the M2 type and the decreased inflammatory response. As a result, myocardial injury caused by sepsis was attenuated. We have also demonstrated that the PI3K/AKT pathway is significantly activated after Piezo1 knockdown, resulting in reduced myocardial dysfunction. Our data indicate that myeloid cell-specific knockdown of Piezo1 can influence macrophage polarization and thus exert cardioprotective effects in a murine model of sepsis, providing potential ideas and targets for the treatment of infectious cardiac dysfunction.

Thrombosis constitutes the principal pathological basis for cardiovascular and cerebrovascular embolic events, with its incidence markedly escalating with advancing age. From a clinical perspective, thrombosis precipitates acute myocardial infarction, ischemic stroke, pulmonary embolism, and disseminated intravascular coagulation (DIC), conditions that frequently culminate in fatal outcomes. Increasing evidence suggests that senescent endothelial cells play a crucial role in mediating age-related thrombotic risk. Senescence-induced endothelial dysfunction compromises the cells' intrinsic anticoagulant capacity, while the acquisition of a senescence-associated secretory phenotype (SASP) further promotes a prothrombotic environment. Accordingly, endothelial cell senescence is integral to both the initiation and progression of thrombosis and its related pathologies. This review systematically summarizes the epidemiology of age-related thrombosis, elucidates the molecular underpinnings of endothelial cell senescence, and explores the intricate pathophysiological interplay between endothelial senescence and thrombosis. In addition, it provides a comprehensive overview of the molecular mechanisms, therapeutic strategies, and prospective targets relevant to vascular endothelial cell senescence, thereby offering new perspectives and theoretical foundations for the advancement of innovative anti-thrombotic interventions that specifically address aging-related pathophysiology.