Abstract 14643: Absence of Hspb1 Increases Endothelium-dependent Protease Activated Receptor 2-mediated Vasorelaxation in a Female but Not Male Arteries
Introduction: Previously, we and others demonstrated that Heat Shock Protein 27 (HSP27; gene: Hspb1) plays an important endothelial cell (EC) role in the synthesis and secretion of VEGF, as well as EC migration and re-endothelialization. As well we noted an important role of estrogens and ovarian function in modulating HSP27 expression. In this study we sought to examine the potential role of HSP27 in vaso-reactivity and blood pressure regulation - specifically looking for differences in male (M) vs. female (F) mice.
Methods/Results: Ex-vivo Study of Aorta: Isolated aortic rings from Hspb1-/-, Hspb1 over-expressing (Hspb1o/e) and wildtype (WT) mice were contracted with phenylephrine (PE) and EC-dependent relaxation responses to Acetylcholine (Ach) and a potent G-protein coupled proteinase-activated receptor-2 (PAR2) agonist, 2-furoyl-LIGRLO-NH2 (2-fLI) were measured in the absence and presence of L-NAME to block NO synthesis. In Hspb1-/- mice NO-independent relaxation was greater in F compared to M mice (p<0.05) as a result of activation of PAR2 (Hspb1-/- 67% vs Controls 29 % and Hspb1o/e 8%; M: Hspb1-/- 6% vs WT 3% and Hspb1o/e 2%) and the muscarinic ACh receptor (F: Hspb1-/- 20% vs WT 4% and Hspb1o/e 1%; M: Hspb1-/- 6% vs WT 3% and Hspb1o/e 1%). NO-independent relaxation was completely inhibited by a combination of potassium channel blockers (Iberiotoxin or IBTx, Tram-34, and Apamin) in M+F WT mice as well as M > F Hspb1-/- mice. The eicosatrienoic acid inhibitor, EEZE, blocked the residual relaxation in F Hspb1-/- mice. The vascular relaxation in Hspb1-/- female mice is contributed partly by both EET’s and calcium activated potassium channels.
Conclusion: Hspb1 expression (HSP27 protein) plays an important sex-specific role in the regulation of vaso-reactivity.
Author Disclosures: V.K. Pulakazhi Venu: None. M. Saifeddine: None. M. El-Daly: None. D. Belke: None. M.D. Hollenberg: None. E.R. O’Brien: None.
- © 2016 by American Heart Association, Inc.