Comparative proteomic analysis of extracellular proteins reveals secretion of T-kininogen from vascular smooth muscle cells in response to incubation with S-enantiomer of propranolol

Propranolol, a nonselective β blocker, exerts blocking activity both on β1 adrenoceptors and β2 ones, with the S-enantiomer being more active than the R-enantiomer. The aim of the study was to investigate the secreted proteins with differential protein expression levels in culture medium of vascular smooth muscle cells (A7r5) incubated separately with individual enantiomers of propranolol using isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional LC-MS/MS approach. Our results indicated that secretion of T-kininogen by S-enantiomer of propranolol incubated cells was greatly enhanced as compared with that of R-enantiomer incubated cells or control cells. It can be inferred that the S-enantiomer of propranolol will induce more IIe-Ser-bradykinin (BK) (T-kinin), the vasoactive peptides. This therefore provides molecular evidence and possible link of T-kininogen with treatment of cardiovascular disease associated with propranolol treatment.