Amphipathic Helical Peptide L37-pA Protects Against Lung Vascular Endothelial Dysfunction Caused by Truncated Oxidized Phospholipids via Antagonism with CD36 Receptor

Am J Respir Cell Mol Biol. 2023 Sep 19. doi: 10.1165/rcmb.2023-0127OC. Online ahead of print.ABSTRACTGeneration of bioactive truncated oxidized phospholipids (Tr-OxPLs) from oxidation of cell membrane or circulating lipoproteins is a common feature of various pathological states. Scavenger receptor CD36 is involved in lipid transport and acts as a ligand for Tr-OxPLs. Interestingly, both Tr-OxPLs and CD36 are involved in endothelial dysfunction-derived acute lung injury but precise mechanistic connections remain unexplored. In the present study, we investigated the role of CD36 in mediating pulmonary endothelial cell (EC) dysfunction caused by Tr-OxPLs. Our results demonstrated that Tr-OxPLs: KOdia-PC, Paz-PC, PGPC, PON-PC, POV-PC, and Lyso-PC caused an acute EC barrier disruption as revealed by measurements of transendothelial electrical resistance and VE-cadherin immunostaining. More importantly, a synthetic amphipathic helical peptide L37pA targeting human CD36 strongly attenuated Tr-OxPLs-induced EC permeability. L37pA also suppressed Tr-OxPLs-induced endothelial inflammatory activation monitored by mRNA expression of inflammatory cytokines/chemokines and adhesion molecules. In addition, L37pA blocked Tr-OxPL-induced NF-B activation and tyrosine phosphorylation of Src kinase and VE-cadherin. Src inhibitor SU6656 attenuated KOdiaPC- induced EC permeability and inflammation, but inhibition of toll-like receptors TLR1, TLR2, TLR4, and TLR6 had no such protective effects. ...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Source Type: research