Heat shock protein expression in cerebral vessels after subarachnoid hemorrhage

Samuel D. Macomson, Colleen M. Brophy, Allison W. Miller, Valerie A. Harris, Ellen G. Shaver, Warren R. Selman, R. Loch Macdonald, E. Sander Connolly, Robert J. Dempsey

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

OBJECTIVE: The mechanisms of cerebral vasospasm after subarachnoid hemorrhage (SAH) remain controversial. Recent data have implicated two small heat shock proteins (HSPs), namely HSP20 and HSP27, in the regulation of vascular tone. Increases in the phosphorylation of HSP20 are associated with vasorelaxation, and increases in the phosphorylation of HSP27 are associated with impaired vasorelaxation. Therefore, we hypothesized that alterations in the expression and/or phosphorylation of these two small HSPs might play a role in cerebral vasospasm after SAH. METHODS: A rat model of endovascular perforation was used to induce SAH. Middle cerebral arteries were harvested from control animals, sham-treated animals, and animals with SAH, 48 hours after SAH induction. Dose-response curves for endothelium-independent (sodium nitroprusside, 10-8 to 10-4 mol/L) and endothelium-dependent (bradykinin, 10-10 to 10-5 mol/L) relaxing agents were recorded ex vivo. Physiological responses were correlated with the expression and phosphorylation of HSP20 and HSP27 by using one- and two-dimensional immunoblots. RESULTS: There was impaired endothelium-independent and endothelium-dependent relaxation in cerebral vessels after SAH. These changes were associated with decreased expression of both total and phosphorylated HSP20 and increases in the amount of phosphorylated HSP27. CONCLUSION: In this model, impaired relaxation of cerebral vessels after SAH was associated with increases in the amount of phosphorylated HSP27 and decreases in the expression and phosphorylation of HSP20. These data are consistent with alterations in the expression and phosphorylation of these small HSPs in other models of vasospasm.

Original languageEnglish (US)
Pages (from-to)204-211
Number of pages8
JournalNeurosurgery
Volume51
Issue number1
DOIs
StatePublished - Jul 1 2002

Fingerprint

Subarachnoid Hemorrhage
Heat-Shock Proteins
Phosphorylation
Small Heat-Shock Proteins
Endothelium
Intracranial Vasospasm
Vasodilation
Middle Cerebral Artery
Nitroprusside
Bradykinin
Blood Vessels

Keywords

  • Endothelium-dependent relaxation
  • Endothelium-independent relaxation
  • Endovascular perforation
  • Heat shock protein
  • Rat
  • Subarachnoid hemorrhage

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Macomson, S. D., Brophy, C. M., Miller, A. W., Harris, V. A., Shaver, E. G., Selman, W. R., ... Dempsey, R. J. (2002). Heat shock protein expression in cerebral vessels after subarachnoid hemorrhage. Neurosurgery, 51(1), 204-211. https://doi.org/10.1097/00006123-200207000-00029

Heat shock protein expression in cerebral vessels after subarachnoid hemorrhage. / Macomson, Samuel D.; Brophy, Colleen M.; Miller, Allison W.; Harris, Valerie A.; Shaver, Ellen G.; Selman, Warren R.; Macdonald, R. Loch; Connolly, E. Sander; Dempsey, Robert J.

In: Neurosurgery, Vol. 51, No. 1, 01.07.2002, p. 204-211.

Research output: Contribution to journalArticle

Macomson, SD, Brophy, CM, Miller, AW, Harris, VA, Shaver, EG, Selman, WR, Macdonald, RL, Connolly, ES & Dempsey, RJ 2002, 'Heat shock protein expression in cerebral vessels after subarachnoid hemorrhage', Neurosurgery, vol. 51, no. 1, pp. 204-211. https://doi.org/10.1097/00006123-200207000-00029
Macomson, Samuel D. ; Brophy, Colleen M. ; Miller, Allison W. ; Harris, Valerie A. ; Shaver, Ellen G. ; Selman, Warren R. ; Macdonald, R. Loch ; Connolly, E. Sander ; Dempsey, Robert J. / Heat shock protein expression in cerebral vessels after subarachnoid hemorrhage. In: Neurosurgery. 2002 ; Vol. 51, No. 1. pp. 204-211.
@article{1833365259e7467a87844d6dd0a32e0c,
title = "Heat shock protein expression in cerebral vessels after subarachnoid hemorrhage",
abstract = "OBJECTIVE: The mechanisms of cerebral vasospasm after subarachnoid hemorrhage (SAH) remain controversial. Recent data have implicated two small heat shock proteins (HSPs), namely HSP20 and HSP27, in the regulation of vascular tone. Increases in the phosphorylation of HSP20 are associated with vasorelaxation, and increases in the phosphorylation of HSP27 are associated with impaired vasorelaxation. Therefore, we hypothesized that alterations in the expression and/or phosphorylation of these two small HSPs might play a role in cerebral vasospasm after SAH. METHODS: A rat model of endovascular perforation was used to induce SAH. Middle cerebral arteries were harvested from control animals, sham-treated animals, and animals with SAH, 48 hours after SAH induction. Dose-response curves for endothelium-independent (sodium nitroprusside, 10-8 to 10-4 mol/L) and endothelium-dependent (bradykinin, 10-10 to 10-5 mol/L) relaxing agents were recorded ex vivo. Physiological responses were correlated with the expression and phosphorylation of HSP20 and HSP27 by using one- and two-dimensional immunoblots. RESULTS: There was impaired endothelium-independent and endothelium-dependent relaxation in cerebral vessels after SAH. These changes were associated with decreased expression of both total and phosphorylated HSP20 and increases in the amount of phosphorylated HSP27. CONCLUSION: In this model, impaired relaxation of cerebral vessels after SAH was associated with increases in the amount of phosphorylated HSP27 and decreases in the expression and phosphorylation of HSP20. These data are consistent with alterations in the expression and phosphorylation of these small HSPs in other models of vasospasm.",
keywords = "Endothelium-dependent relaxation, Endothelium-independent relaxation, Endovascular perforation, Heat shock protein, Rat, Subarachnoid hemorrhage",
author = "Macomson, {Samuel D.} and Brophy, {Colleen M.} and Miller, {Allison W.} and Harris, {Valerie A.} and Shaver, {Ellen G.} and Selman, {Warren R.} and Macdonald, {R. Loch} and Connolly, {E. Sander} and Dempsey, {Robert J.}",
year = "2002",
month = "7",
day = "1",
doi = "10.1097/00006123-200207000-00029",
language = "English (US)",
volume = "51",
pages = "204--211",
journal = "Neurosurgery",
issn = "0148-396X",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Heat shock protein expression in cerebral vessels after subarachnoid hemorrhage

AU - Macomson, Samuel D.

AU - Brophy, Colleen M.

AU - Miller, Allison W.

AU - Harris, Valerie A.

AU - Shaver, Ellen G.

AU - Selman, Warren R.

AU - Macdonald, R. Loch

AU - Connolly, E. Sander

AU - Dempsey, Robert J.

PY - 2002/7/1

Y1 - 2002/7/1

N2 - OBJECTIVE: The mechanisms of cerebral vasospasm after subarachnoid hemorrhage (SAH) remain controversial. Recent data have implicated two small heat shock proteins (HSPs), namely HSP20 and HSP27, in the regulation of vascular tone. Increases in the phosphorylation of HSP20 are associated with vasorelaxation, and increases in the phosphorylation of HSP27 are associated with impaired vasorelaxation. Therefore, we hypothesized that alterations in the expression and/or phosphorylation of these two small HSPs might play a role in cerebral vasospasm after SAH. METHODS: A rat model of endovascular perforation was used to induce SAH. Middle cerebral arteries were harvested from control animals, sham-treated animals, and animals with SAH, 48 hours after SAH induction. Dose-response curves for endothelium-independent (sodium nitroprusside, 10-8 to 10-4 mol/L) and endothelium-dependent (bradykinin, 10-10 to 10-5 mol/L) relaxing agents were recorded ex vivo. Physiological responses were correlated with the expression and phosphorylation of HSP20 and HSP27 by using one- and two-dimensional immunoblots. RESULTS: There was impaired endothelium-independent and endothelium-dependent relaxation in cerebral vessels after SAH. These changes were associated with decreased expression of both total and phosphorylated HSP20 and increases in the amount of phosphorylated HSP27. CONCLUSION: In this model, impaired relaxation of cerebral vessels after SAH was associated with increases in the amount of phosphorylated HSP27 and decreases in the expression and phosphorylation of HSP20. These data are consistent with alterations in the expression and phosphorylation of these small HSPs in other models of vasospasm.

AB - OBJECTIVE: The mechanisms of cerebral vasospasm after subarachnoid hemorrhage (SAH) remain controversial. Recent data have implicated two small heat shock proteins (HSPs), namely HSP20 and HSP27, in the regulation of vascular tone. Increases in the phosphorylation of HSP20 are associated with vasorelaxation, and increases in the phosphorylation of HSP27 are associated with impaired vasorelaxation. Therefore, we hypothesized that alterations in the expression and/or phosphorylation of these two small HSPs might play a role in cerebral vasospasm after SAH. METHODS: A rat model of endovascular perforation was used to induce SAH. Middle cerebral arteries were harvested from control animals, sham-treated animals, and animals with SAH, 48 hours after SAH induction. Dose-response curves for endothelium-independent (sodium nitroprusside, 10-8 to 10-4 mol/L) and endothelium-dependent (bradykinin, 10-10 to 10-5 mol/L) relaxing agents were recorded ex vivo. Physiological responses were correlated with the expression and phosphorylation of HSP20 and HSP27 by using one- and two-dimensional immunoblots. RESULTS: There was impaired endothelium-independent and endothelium-dependent relaxation in cerebral vessels after SAH. These changes were associated with decreased expression of both total and phosphorylated HSP20 and increases in the amount of phosphorylated HSP27. CONCLUSION: In this model, impaired relaxation of cerebral vessels after SAH was associated with increases in the amount of phosphorylated HSP27 and decreases in the expression and phosphorylation of HSP20. These data are consistent with alterations in the expression and phosphorylation of these small HSPs in other models of vasospasm.

KW - Endothelium-dependent relaxation

KW - Endothelium-independent relaxation

KW - Endovascular perforation

KW - Heat shock protein

KW - Rat

KW - Subarachnoid hemorrhage

UR - http://www.scopus.com/inward/record.url?scp=0036664925&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036664925&partnerID=8YFLogxK

U2 - 10.1097/00006123-200207000-00029

DO - 10.1097/00006123-200207000-00029

M3 - Article

VL - 51

SP - 204

EP - 211

JO - Neurosurgery

JF - Neurosurgery

SN - 0148-396X

IS - 1

ER -