VALVULAR TOXICITY

Cardiac valves are a set of connective tissue structures that enable the unidirectional, hemodynamic flow of blood through the chambers of the heart. Valves consist of a surface layer of valvular endocardial endothelial cells (VEC), valvular interstitial cells (VIC), and the interstitial extracellular matrix (ECM). In response to injury, hemodynamic stresses or drugs, VIC can become become activated and transform into a myofibroblastic cell type. These cells express smooth muscle actin (α-SMA) and are capable of producing and remodeling excess ECM, release proinflammatory mediators and lead to valve calcification. These changes alter the mechanical properties of the valves and their hemodynamic response, leading to a number of pathological conditions.

In one example of such a situation, the prescription drug combination of fenfluramine and phentermine (fen-phen), approved for weight loss in 1996, was withdrawn from the market in 1997 after numerous reports of valve lesions.

Using isolated VIC, AVIVA scientists can measure the effect of pharmaceutical compounds on the activation state of the cells, the initial step in drug-induced valvulopathy.