-Cytosolic PLA2-targeting drug reduces vascular calcification-
Endothelial dysfunction is a hallmark of cardiovascular disease (CVD) that ultimately leads to thrombosis and vascular occlusion. Despite being a leading cause of death worldwide, there has been a paucity of promising drug targets to prevent and/or minimize CVD. Joost Schanstra, Trang Luong, Manousos Makridakis, Sophie Van Linthout and colleagues evaluated the arterial proteome of patients with advanced and early CVD to identify a CVD-associated signature with potential to be targeted by bioactive small molecules. Of the candidate drugs, cytosolic phospholipase A2 (cPLA2) inhibitor AACOCF3 was a top candidate to reverse in-silico the proteomic signature of advanced CVD, as cPLA2 was notably increased in these patients. In a murine cholecalciferol overload model of CVD, AACOF3 reduced vascular calcification via inhibition of osteoinductive signaling. In addition to identifying a CVD drug candidate, these results support application of proteomic signatures in drug repurposing approaches to identify drug candidates for other complex diseases.
If you want to read the details of this exciting paper,……it is “open access” and can be found here.