Arterial Motives?

Safety pharmacology is an essential part of drug development aiming to identify, evaluate and investigate undesirable properties of a drug primarily prior to clinical trials. Successful screening strategies to detect cardiovascular liabilities have been implemented, but there is room for further refinement ¹. In this perspective, arterial stiffness is an interesting, blood pressure-independent factor to predict the risk of cardiovascular disease, but has not been widely considered in safety pharmacology. Historically, arterial stiffness was considered to reflect (passive) biomechanical properties of the artery wall, such as the ratio of compliant elastin versus stiffer collagen fibers. Our PHYSPHAR research group has developed a unique and proprietary organ set-up, as seen in the image (i.e., the Rodent Oscillatory Tension Set-up to study Arterial Compliance, ROTSAC) that enables ex vivo determination of intrinsic arterial stiffness, independent of confounding factors, such as blood pressure or heart rate ². This novel technological platform holds potential to directly evaluate acute effects of chosen drugs, untangling their underlying mechanisms.  

Could this be the tool us scientists have been waiting for? Join us on our journey to find out! 

References:

1. Guns, P. D., Guth, B. D., Braam, S., Kosmidis, G., Matsa, E., Delaunois, A.,Valentin, J. P. (2020). INSPIRE: A European training network to foster research and training in cardiovascular safety pharmacology. J Pharmacol Toxicol Methods, 106889. doi:10.1016/j.vascn.2020.106889 
2. Le loup, A. J. A., Van Hove, C. E., De Moudt, S., De Meyer, G. R. Y., De Keulenaer,G. W., & Fransen, P. (2019). Vascular smooth muscle cell contraction and relaxation in the isolated aorta: a critical regulator of large artery compliance .Physiol Rep, 7(4), e13934. doi:10.14814/phy2.13934