Manasa Reddy Gummi

Medial vascular calcification (MAC) is characterized by the deposition of hydroxyapatite (HAP) in the medial layer of the vessel wall, leading to disruption of vessel integrity and vascular stiffness. Because currently no direct therapeutic interventions for MAC are available, studying the MAC pathogenesis is of high research interest. Several methods exist to measure and describe the pathophysiological processes in the vessel wall, such as histological staining and gene expression. However, no method describing the physiological properties of the arterial wall is currently available. This study aims to close that gap and validate a method to measure the biomechanical properties of the arterial wall during vascular calcification. Therefore, a stress–stretch curve is monitored using small-vessel-myography upon ex vivo calcification of rat aortic tissue. The measurement of biomechanical properties could help to gain further insights into vessel integrity during calcification progression.

Vessel calcification is characterized by the precipitation of hydroxyapatite (HAP) in the vasculature. Currently, no causal therapy exists to reduce or prevent vessel calcification. Studying the underlying pathways within vascular smooth muscle cells and testing pharmacological intervention is a major challenge in the vascular research field. This study aims to establish a rapid and efficient working protocol for specific HAP detection in cells and tissue using the synthetic bisphosphonate fluorescence dye OsteoSense™. This protocol facilitates especially early quantification of the fluorescence signal and permits co-staining with other markers of interest, enabling smaller experimental set-ups with lesser primary cells consumption and fast workflows. The fluorescence-based detection of vascular calcification with OsteoSense™ combines a high specificity with improved sensitivity. Therefore, this methodology can improve research of the pathogenesis of vascular calcification, especially for testing the therapeutic benefit of inhibitors in the case of in vitro and ex vivo settings.

Vascular calcification is a multifaceted disease and a significant contributor to cardiovascular morbidity and mortality. The calcification deposits in the vessel wall can vary in size and localization. Various pathophysiological pathways may be involved in disease progression. With respect to the calcification diversity, a great number of research models and detection methods have been established in basic research, relying mostly on rodent models. The aim of this review is to provide an overview of the currently available rodent models and quantification methods for vascular calcification, emphasizing animal burden and assessing prospects to use available methods in a way to address the 3R principles of Russel and Burch: “Replace, Reduce and Refine”.