Figure 6.

Schematic summary: chronic use of pergolide or dexfenfluramine activates p38 MAPK in valvular cells. Specifically, pergolide triggers AMPK- and miR-107-dependent homeostasis processes, whereas dexfenfluramine affects cytoskeletal organization. Drug-induced alterations of valve homeostasis and cytoskeleton are associated with net inhibition of biosynthetic processes that reflect valve metabolic reprogramming, leading to ECM remodeling and valvulopathy. Gray arrows represent hypothetical links.