Simulating Arterial Stress for Rapid Evaluation of Antivascular Calcification Therapies from Herbal Extracts.

Abstract

Vascular calcification severely disrupts cardiovascular hemodynamics, leading to high rates of morbidity and mortality. Despite their clinical impact, the development of effective treatments remains limited, underscoring an urgent need for efficient and reliable drug screening methods. Vascular smooth muscle cells (VSMCs) are known to play a central role in driving the calcification process, undergoing an osteogenic transition in response to pathological conditions. To mimic this process, we developed a cyclic stretching device that replicates the physiological mechanical stresses experienced by VSMCs during arterial pulsation. This device dramatically accelerates the osteogenic transition of VSMCs, reducing phenotypic switching from 13 days under static conditions to just 4 h. Using this device, we screened 20 herbal extracts for anticalcification properties and identifiedSalvia miltiorrhizaas a candidate with therapeutic potential that inhibits VSMC osteogenic transdifferentiation in vitro. The anticalcification efficacy ofSalvia miltiorrhizawas further validated in a vitamin D-induced rat model of cardiovascular calcification, highlighting its translational potential. This screening platform provides a rapid and physiologically relevant method for evaluating potential antivascular calcification therapies, significantly improving the efficiency of drug discovery for clinical translation.