Skip to Main content Skip to Navigation
Journal articles

Systems biology identifies cytosolic PLA2 as a target in vascular calcification treatment

Abstract : Although cardiovascular disease (CVD) is the leading cause of morbimortality worldwide, promising new drug candidates are lacking. We compared the arterial high-resolution proteome of patients with advanced versus early-stage CVD to predict, from a library of small bioactive molecules, drug candidates able to reverse this disease signature. Of the approximately 4000 identified proteins, 100 proteins were upregulated and 52 were downregulated in advanced-stage CVD. Arachidonyl trifluoromethyl ketone (AACOCF3), a cytosolic phospholipase A2 (cPLA2) inhibitor was predicted as the top drug able to reverse the advanced-stage CVD signature. Vascular cPLA2 expression was increased in patients with advanced-stage CVD. Treatment with AACOCF3 significantly reduced vascular calcification in a cholecalciferol-overload mouse model and inhibited osteoinductive signaling in vivo and in vitro in human aortic smooth muscle cells. In conclusion, using a systems biology approach, we have identified a potentially new compound that prevented typical vascular calcification in CVD in vivo. Apart from the clear effect of this approach in CVD, such strategy should also be able to generate novel drug candidates in other complex diseases.
Document type :
Journal articles
Complete list of metadata
Contributor : Jean Sébastien Saulnier-Blache <>
Submitted on : Wednesday, June 23, 2021 - 11:50:58 AM
Last modification on : Wednesday, June 30, 2021 - 9:40:15 PM


 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document



Joost Schanstra, Trang T.D. Luong, Manousos Makridakis, Sophie van Linthout, Vasiliki Lygirou, et al.. Systems biology identifies cytosolic PLA2 as a target in vascular calcification treatment. JCI Insight, American Society for Clinical Investigation, 2019, 4 (10), pp.e125638. ⟨10.1172/jci.insight.125638⟩. ⟨inserm-03268526⟩



Record views