PECAM-1 mediates NO-dependent dilation of arterioles to high temporal gradients of shear stress

Zsolt Bagi, John A. Frangos, Jiunn Chern Yeh, Charles R. White, Gabor Kaley, Akos Koller

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Objective - In response to changes in wall shear stress (WSS) the vascular endothelium releases several factors, among others nitric oxide. On the basis of studies of endothelial cells in culture, suggesting that platelet endothelial cell adhesion molecule-1 (PECAM-1) is specifically involved in sensing and coupling high temporal gradients of fluid shear stress with activation of eNOS, we hypothesized that dilations of isolated skeletal muscle arterioles from PECAM-1 knockout mice (PECAM-KO) will be reduced to rapid increases in WSS elicited by increases in perfusate flow. Methods and Results - Small and large step increases in flow resulted in substantial dilations in arterioles of WT mice (45±4%), but they were markedly reduced in arterioles of PECAM-KO mice (22±5%). The initial slope of dilations, when WSS increased rapidly, was greater in vessels of WT than those of PECAM-KO mice (slopes: 0.378 and 0.094, respectively), whereas the second phase of dilations, when flow/shear stress was steady, was similar in the 2 groups (slopes: 0.085 and 0.094, respectively). Inhibition of eNOS significantly reduced the initial phase of dilations in arterioles from WT, but not from those of PECAM-KO mice. The calcium ionophore A23187 elicited similar NO-mediated dilation in both WT and PECAM-KO mice. Conclusions - In isolated arterioles of PECAM-KO mice activation of eNOS and consequent dilation by agonists is maintained, but the dilation to high temporal gradients of wall shear stress elicited by increases in perfusate flow is reduced. Thus, we propose that PECAM-1 plays an important role in the ability of the endothelium to sense and couple high temporal gradients of wall shear stress to NO-mediated arteriolar dilation during sudden changes in blood flow in vivo.

Original languageEnglish (US)
Pages (from-to)1590-1595
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume25
Issue number8
DOIs
StatePublished - Aug 1 2005

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CD31 Antigens
Arterioles
Dilatation
Knockout Mice
Calcium Ionophores
Vascular Endothelium
Calcimycin
Endothelium
Nitric Oxide
Skeletal Muscle
Endothelial Cells
Cell Culture Techniques

Keywords

  • Arteriole
  • Endothelium
  • Flow-induced dilation
  • Nitric oxide
  • PECAM-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

PECAM-1 mediates NO-dependent dilation of arterioles to high temporal gradients of shear stress. / Bagi, Zsolt; Frangos, John A.; Yeh, Jiunn Chern; White, Charles R.; Kaley, Gabor; Koller, Akos.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 25, No. 8, 01.08.2005, p. 1590-1595.

Research output: Contribution to journalArticle

Bagi, Zsolt ; Frangos, John A. ; Yeh, Jiunn Chern ; White, Charles R. ; Kaley, Gabor ; Koller, Akos. / PECAM-1 mediates NO-dependent dilation of arterioles to high temporal gradients of shear stress. In: Arteriosclerosis, thrombosis, and vascular biology. 2005 ; Vol. 25, No. 8. pp. 1590-1595.
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abstract = "Objective - In response to changes in wall shear stress (WSS) the vascular endothelium releases several factors, among others nitric oxide. On the basis of studies of endothelial cells in culture, suggesting that platelet endothelial cell adhesion molecule-1 (PECAM-1) is specifically involved in sensing and coupling high temporal gradients of fluid shear stress with activation of eNOS, we hypothesized that dilations of isolated skeletal muscle arterioles from PECAM-1 knockout mice (PECAM-KO) will be reduced to rapid increases in WSS elicited by increases in perfusate flow. Methods and Results - Small and large step increases in flow resulted in substantial dilations in arterioles of WT mice (45±4{\%}), but they were markedly reduced in arterioles of PECAM-KO mice (22±5{\%}). The initial slope of dilations, when WSS increased rapidly, was greater in vessels of WT than those of PECAM-KO mice (slopes: 0.378 and 0.094, respectively), whereas the second phase of dilations, when flow/shear stress was steady, was similar in the 2 groups (slopes: 0.085 and 0.094, respectively). Inhibition of eNOS significantly reduced the initial phase of dilations in arterioles from WT, but not from those of PECAM-KO mice. The calcium ionophore A23187 elicited similar NO-mediated dilation in both WT and PECAM-KO mice. Conclusions - In isolated arterioles of PECAM-KO mice activation of eNOS and consequent dilation by agonists is maintained, but the dilation to high temporal gradients of wall shear stress elicited by increases in perfusate flow is reduced. Thus, we propose that PECAM-1 plays an important role in the ability of the endothelium to sense and couple high temporal gradients of wall shear stress to NO-mediated arteriolar dilation during sudden changes in blood flow in vivo.",
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T1 - PECAM-1 mediates NO-dependent dilation of arterioles to high temporal gradients of shear stress

AU - Bagi, Zsolt

AU - Frangos, John A.

AU - Yeh, Jiunn Chern

AU - White, Charles R.

AU - Kaley, Gabor

AU - Koller, Akos

PY - 2005/8/1

Y1 - 2005/8/1

N2 - Objective - In response to changes in wall shear stress (WSS) the vascular endothelium releases several factors, among others nitric oxide. On the basis of studies of endothelial cells in culture, suggesting that platelet endothelial cell adhesion molecule-1 (PECAM-1) is specifically involved in sensing and coupling high temporal gradients of fluid shear stress with activation of eNOS, we hypothesized that dilations of isolated skeletal muscle arterioles from PECAM-1 knockout mice (PECAM-KO) will be reduced to rapid increases in WSS elicited by increases in perfusate flow. Methods and Results - Small and large step increases in flow resulted in substantial dilations in arterioles of WT mice (45±4%), but they were markedly reduced in arterioles of PECAM-KO mice (22±5%). The initial slope of dilations, when WSS increased rapidly, was greater in vessels of WT than those of PECAM-KO mice (slopes: 0.378 and 0.094, respectively), whereas the second phase of dilations, when flow/shear stress was steady, was similar in the 2 groups (slopes: 0.085 and 0.094, respectively). Inhibition of eNOS significantly reduced the initial phase of dilations in arterioles from WT, but not from those of PECAM-KO mice. The calcium ionophore A23187 elicited similar NO-mediated dilation in both WT and PECAM-KO mice. Conclusions - In isolated arterioles of PECAM-KO mice activation of eNOS and consequent dilation by agonists is maintained, but the dilation to high temporal gradients of wall shear stress elicited by increases in perfusate flow is reduced. Thus, we propose that PECAM-1 plays an important role in the ability of the endothelium to sense and couple high temporal gradients of wall shear stress to NO-mediated arteriolar dilation during sudden changes in blood flow in vivo.

AB - Objective - In response to changes in wall shear stress (WSS) the vascular endothelium releases several factors, among others nitric oxide. On the basis of studies of endothelial cells in culture, suggesting that platelet endothelial cell adhesion molecule-1 (PECAM-1) is specifically involved in sensing and coupling high temporal gradients of fluid shear stress with activation of eNOS, we hypothesized that dilations of isolated skeletal muscle arterioles from PECAM-1 knockout mice (PECAM-KO) will be reduced to rapid increases in WSS elicited by increases in perfusate flow. Methods and Results - Small and large step increases in flow resulted in substantial dilations in arterioles of WT mice (45±4%), but they were markedly reduced in arterioles of PECAM-KO mice (22±5%). The initial slope of dilations, when WSS increased rapidly, was greater in vessels of WT than those of PECAM-KO mice (slopes: 0.378 and 0.094, respectively), whereas the second phase of dilations, when flow/shear stress was steady, was similar in the 2 groups (slopes: 0.085 and 0.094, respectively). Inhibition of eNOS significantly reduced the initial phase of dilations in arterioles from WT, but not from those of PECAM-KO mice. The calcium ionophore A23187 elicited similar NO-mediated dilation in both WT and PECAM-KO mice. Conclusions - In isolated arterioles of PECAM-KO mice activation of eNOS and consequent dilation by agonists is maintained, but the dilation to high temporal gradients of wall shear stress elicited by increases in perfusate flow is reduced. Thus, we propose that PECAM-1 plays an important role in the ability of the endothelium to sense and couple high temporal gradients of wall shear stress to NO-mediated arteriolar dilation during sudden changes in blood flow in vivo.

KW - Arteriole

KW - Endothelium

KW - Flow-induced dilation

KW - Nitric oxide

KW - PECAM-1

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