Heat shock protein‐27 and sex‐selective regulation of muscarinic and proteinase‐activated receptor 2‐mediated vasodilatation: differential sensitivity to endothelial NOS inhibition

Venu, Vivek Krishna Pulakazhi; Saifeddine, Mahmoud; Mihara, Koichiro; El‐Daly, Mahmoud; Belke, Darrell D.; Dean, Jonathan L. E.; O'Brien, Edward R.; Hirota, Simon A.; Hollenberg, Morley D.

doi:10.1111/bph.14200

Cited by 7 publications

(3 citation statements)

References 59 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with a role for HSP27 in barrier recovery, we showed that treatment of female mice with J2 enhanced vascular leakage induced by the activation of PAR1 but failed to affect VEGF-induced vascular leakage. Note that a previous study using HSPB1 -null mice ( HSPB1 encodes HSP27) observed sex-selective sensitivity to endothelial nitric oxide synthase inhibition, with female mice exhibiting greater sensitivity than male mice ( 40 ). These findings raise the possibility that modulation of vascular leakage observed with J2 may exhibit sex-selective sensitivity, but this has not been tested.…”

Section: Discussionmentioning

confidence: 91%

Heat shock protein 27 activity is linked to endothelial barrier recovery after proinflammatory GPCR-induced disruption

et al. 2021

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 91%

Heat shock protein 27 activity is linked to endothelial barrier recovery after proinflammatory GPCR-induced disruption

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Wire-myograph vascular bioassays. Isometric tension studies using a wire myograph were performed, as described previously (5,8,13). In brief, descending aorta tissue was cut into 2-mm-long rings as outlined above and mounted in the myograph.…”

Section: Methodsmentioning

confidence: 99%

The pregnane X receptor and its microbiota-derived ligand indole 3-propionic acid regulate endothelium-dependent vasodilation

Venu

Saifeddine

Mihara

et al. 2019

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

View full text Add to dashboard Cite

We proposed that circulating metabolites generated by the intestinal microbiota can affect vascular function. One such metabolite, indole 3-propionic acid (IPA), can activate the pregnane X receptor(PXR), a xenobiotic-activated nuclear receptor present in many tissues, including the vascular endothelium. We hypothesized that IPA could regulate vascular function by modulating PXR activity. To test this, Pxr+/+ mice were administered broad-spectrum antibiotics for 2 wk with IPA supplementation. Vascular function was evaluated by bioassay using aorta and pulmonary artery ring tissue from antibiotic-treated Pxr+/+ and Pxr−/−mice, supplemented with IPA, and using aorta tissue maintained in organ culture for 24 h in the presence of IPA. Endothelium-dependent, nitric oxide(NO)-mediated muscarinic and proteinase-activated receptor 2(PAR2)-stimulated vasodilation was assessed. Endothelial nitric oxide synthase (eNOS) abundance was evaluated in intact tissue or in aorta-derived endothelial cell cultures from Pxr+/+ and Pxr−/− mice, and vascular Pxr levels were assessed in tissues obtained from Pxr+/+ mice treated with antibiotics and supplemented with IPA. Antibiotic-treated Pxr+/+ mice exhibited enhanced agonist-induced endothelium-dependent vasodilation, which was phenocopied by tissues from either Pxr−/− or germ-free mice. IPA exposure reduced the vasodilatory responses in isolated and cultured vessels. No effects of IPA were observed for tissues obtained from Pxr−/− mice. Serum nitrate levels were increased in antibiotic-treated Pxr+/+and Pxr−/− mice. eNOS abundance was increased in aorta tissues and cultured endothelium from Pxr−/− mice. PXR stimulation reduced eNOS expression in cultured endothelial cells from Pxr+/+ but not Pxr−/− mice. The microbial metabolite IPA, via the PXR, plays a key role in regulating endothelial function. Furthermore, antibiotic treatment changes PXR-mediated vascular endothelial responsiveness by upregulating eNOS.

show abstract

“…However, further research is needed to translate hypoxic exposure interventions to the clinical setting. In a study of HSP27-deficient and overexpressing mice, Venu et al (105) found that HSP27 can affect mRNA levels of endothelial nitric oxide synthase (eNOS) and soluble guanylate cyclase, as well as the proportion of vasodilation that is sensitive to the action of L-N G -nitro arginine methyl ester (L-NAME), thereby influencing nitric oxide-mediated vascular relaxation by regulating intact vascular endothelial function.…”

Section: The Therapeutic Intervention Of Hsp27 41 Atherosclerosismentioning

confidence: 99%

Mechanistic insights into heat shock protein 27, a potential therapeutic target for cardiovascular diseases

Zou

Shi

Liu

et al. 2023

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Heat shock protein 27 (HSP27) is a small chaperone protein that is overexpressed in a variety of cellular stress states. It is involved in regulating proteostasis and protecting cells from multiple sources of stress injury by stabilizing protein conformation and promoting the refolding of misfolded proteins. Previous studies have confirmed that HSP27 is involved in the development of cardiovascular diseases and plays an important regulatory role in this process. Herein, we comprehensively and systematically summarize the involvement of HSP27 and its phosphorylated form in pathophysiological processes, including oxidative stress, inflammatory responses, and apoptosis, and further explore the potential mechanisms and possible roles of HSP27 in the diagnosis and treatment of cardiovascular diseases. Targeting HSP27 is a promising future strategy for the treatment of cardiovascular diseases.

show abstract

Heat shock protein‐27 and sex‐selective regulation of muscarinic and proteinase‐activated receptor 2‐mediated vasodilatation: differential sensitivity to endothelial NOS inhibition

Abstract: HSPB1 can regulate intact vascular endothelial function to affect NO-mediated vascular relaxation, especially in females.

Cited by 7 publications

References 59 publications

Heat shock protein 27 activity is linked to endothelial barrier recovery after proinflammatory GPCR-induced disruption

Heat shock protein 27 activity is linked to endothelial barrier recovery after proinflammatory GPCR-induced disruption

The pregnane X receptor and its microbiota-derived ligand indole 3-propionic acid regulate endothelium-dependent vasodilation

Mechanistic insights into heat shock protein 27, a potential therapeutic target for cardiovascular diseases

Contact Info

Product

Resources

About