التفاصيل البيبلوغرافية
| العنوان: |
Heat shock protein-27 and sex-selective regulation of muscarinic and proteinase-activated receptor 2-mediated vasodilatation: differential sensitivity to endothelial NOS inhibition. |
| المؤلفون: |
Pulakazhi Venu, Vivek Krishna1,2 vivek.pulakazhivenu@ucalgary.ca, Saifeddine, Mahmoud1, Mihara, Koichiro1, El‐Daly, Mahmoud1,3, Belke, Darrell2, Dean, Jonathan L E4, O'Brien, Edward R2, Hirota, Simon A1, Hollenberg, Morley D1,5 mhollenb@ucalgary.ca, El-Daly, Mahmoud6,7 (AUTHOR) |
| المصدر: |
British Journal of Pharmacology. Jun2018, Vol. 175 Issue 11, p2063-2076. 14p. 6 Graphs. |
| مصطلحات موضوعية: |
*HEAT shock proteins, *MUSCARINIC receptors, *PROTEINASES, *ENDOTHELIAL cells, *MESSENGER RNA |
| مستخلص: |
Background and Purpose: Previously, we demonstrated that exogenous heat shock protein 27 (HSP27/gene, HSPB1) treatment of human endothelial progenitor cells (EPCs) increases the synthesis and secretion of VEGF, improves EPC-migration/re-endothelialization and decreases neo-intima formation, suggesting a role for HSPB1 in regulating EPC function. We hypothesized that HSPB1 also affects mature endothelial cells (ECs) to alter EC-mediated vasoreactivity in vivo. Our work focused on endothelial NOS (eNOS)/NO-dependent relaxation induced by ACh and the coagulation pathway-activated receptor, proteinase-activated receptor 2 (PAR2).Experimental Approach: Aorta rings from male and female wild-type, HSPB1-null and HSPB1 overexpressing (HSPB1o/e) mice were contracted with phenylephrine, and NOS-dependent relaxation responses to ACh and PAR2 agonist, 2-furoyl-LIGRLO-NH2 , were measured without and with L-NAME and ODQ, either alone or in combination to block NO synthesis/action. Tissues from female HSPB1-null mice were treated in vitro with recombinant HSP27 and then used for bioassay as above. Furthermore, oestrogen-specific effects were evaluated using a bioassay of aorta isolated from ovariectomized mice.Key Results: Relative to males, HSPB1-null female mice exhibited an increased L-NAME-resistant relaxation induced by activation of either PAR2 or muscarinic ACh receptors that was blocked in the concurrent presence of both L-NAME and ODQ. mRNAs (qPCR) for eNOS and ODQ-sensitive guanylyl-cyclase were increased in females versus males. Treatment of isolated aorta tissue with HSPB1 improved tissue responsiveness in the presence of L-NAME. Ovariectomy did not affect NO sensitivity, supporting an oestrogen-independent role for HSPB1.Conclusions and Implications: HSPB1 can regulate intact vascular endothelial function to affect NO-mediated vascular relaxation, especially in females. [ABSTRACT FROM AUTHOR] |
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