Stress upregulates arterial matrix metalloproteinase expression and activity via endothelin A receptor activation

Adviye Ergul, Vera Portik-Dobos, Ararat D. Giulumian, Mariela M. Molero, Leslie C. Fuchs

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Degradation of the extracellular matrix proteins by matrix metalloproteinases (MMP) is an important regulatory step in the vascular remodeling process. Recent studies demonstrated that ETA receptors regulate cardiac MMP activity and fibrosis in DOCA-salt hypertension. However, little is known about endothelin (ET)-1 regulation of vascular MMP activity in hypertension. Thus early changes in ET-1-mediated regulation of MMP activity were measured in borderline hypertensive rats that develop impaired vasorelaxation and hypertension with chronic exposure to stress. Experiments were performed after 10 days of exposure to the behavioral stressor, air-jet stress, but before the onset of stress-induced hypertension. Study groups were 1) control (n = 8); 2) air-jet stress for 10 days (n = 8); 3) control plus ETA antagonist ABT-627 (n = 4), and 4) air-jet stress plus ETA antagonist (n = 4). MMP activity in the thoracic aorta was assessed by gelatin zymography. MMP protein and tissue ET-1 levels were evaluated by immunohistochemistry, and ET receptor density was determined by immunoblotting. Exposure to stress caused a twofold increase in plasma ET-1 levels (P < 0.05), and there was increased ET-1 staining at the tissue level. Total MMP activity and expression of MMP-2 and MMP-9 were increased in the stress group. ETA receptor antagonism prevented the increase in MMP expression and activation in the stress group. These results provide evidence that the MMP system is activated before the development of hypertension and ET-1 mediates these early events in vascular remodeling.

Original languageEnglish (US)
Pages (from-to)H2225-H2232
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number5 54-5
StatePublished - Nov 1 2003

Fingerprint

Endothelin A Receptors
Matrix Metalloproteinases
Up-Regulation
Endothelin-1
Hypertension
Air
Desoxycorticosterone Acetate
Endothelin Receptors
Extracellular Matrix Proteins
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Gelatin
Thoracic Aorta
Immunoblotting
Vasodilation
Blood Vessels
Fibrosis
Salts
Immunohistochemistry
Staining and Labeling

Keywords

  • ABT-627
  • Endothelin-1

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Stress upregulates arterial matrix metalloproteinase expression and activity via endothelin A receptor activation. / Ergul, Adviye; Portik-Dobos, Vera; Giulumian, Ararat D.; Molero, Mariela M.; Fuchs, Leslie C.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 285, No. 5 54-5, 01.11.2003, p. H2225-H2232.

Research output: Contribution to journalArticle

Ergul, Adviye ; Portik-Dobos, Vera ; Giulumian, Ararat D. ; Molero, Mariela M. ; Fuchs, Leslie C. / Stress upregulates arterial matrix metalloproteinase expression and activity via endothelin A receptor activation. In: American Journal of Physiology - Heart and Circulatory Physiology. 2003 ; Vol. 285, No. 5 54-5. pp. H2225-H2232.
@article{ab2989cc5ec846a3a258695385cea434,
title = "Stress upregulates arterial matrix metalloproteinase expression and activity via endothelin A receptor activation",
abstract = "Degradation of the extracellular matrix proteins by matrix metalloproteinases (MMP) is an important regulatory step in the vascular remodeling process. Recent studies demonstrated that ETA receptors regulate cardiac MMP activity and fibrosis in DOCA-salt hypertension. However, little is known about endothelin (ET)-1 regulation of vascular MMP activity in hypertension. Thus early changes in ET-1-mediated regulation of MMP activity were measured in borderline hypertensive rats that develop impaired vasorelaxation and hypertension with chronic exposure to stress. Experiments were performed after 10 days of exposure to the behavioral stressor, air-jet stress, but before the onset of stress-induced hypertension. Study groups were 1) control (n = 8); 2) air-jet stress for 10 days (n = 8); 3) control plus ETA antagonist ABT-627 (n = 4), and 4) air-jet stress plus ETA antagonist (n = 4). MMP activity in the thoracic aorta was assessed by gelatin zymography. MMP protein and tissue ET-1 levels were evaluated by immunohistochemistry, and ET receptor density was determined by immunoblotting. Exposure to stress caused a twofold increase in plasma ET-1 levels (P < 0.05), and there was increased ET-1 staining at the tissue level. Total MMP activity and expression of MMP-2 and MMP-9 were increased in the stress group. ETA receptor antagonism prevented the increase in MMP expression and activation in the stress group. These results provide evidence that the MMP system is activated before the development of hypertension and ET-1 mediates these early events in vascular remodeling.",
keywords = "ABT-627, Endothelin-1",
author = "Adviye Ergul and Vera Portik-Dobos and Giulumian, {Ararat D.} and Molero, {Mariela M.} and Fuchs, {Leslie C.}",
year = "2003",
month = "11",
day = "1",
language = "English (US)",
volume = "285",
pages = "H2225--H2232",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "5 54-5",

}

TY - JOUR

T1 - Stress upregulates arterial matrix metalloproteinase expression and activity via endothelin A receptor activation

AU - Ergul, Adviye

AU - Portik-Dobos, Vera

AU - Giulumian, Ararat D.

AU - Molero, Mariela M.

AU - Fuchs, Leslie C.

PY - 2003/11/1

Y1 - 2003/11/1

N2 - Degradation of the extracellular matrix proteins by matrix metalloproteinases (MMP) is an important regulatory step in the vascular remodeling process. Recent studies demonstrated that ETA receptors regulate cardiac MMP activity and fibrosis in DOCA-salt hypertension. However, little is known about endothelin (ET)-1 regulation of vascular MMP activity in hypertension. Thus early changes in ET-1-mediated regulation of MMP activity were measured in borderline hypertensive rats that develop impaired vasorelaxation and hypertension with chronic exposure to stress. Experiments were performed after 10 days of exposure to the behavioral stressor, air-jet stress, but before the onset of stress-induced hypertension. Study groups were 1) control (n = 8); 2) air-jet stress for 10 days (n = 8); 3) control plus ETA antagonist ABT-627 (n = 4), and 4) air-jet stress plus ETA antagonist (n = 4). MMP activity in the thoracic aorta was assessed by gelatin zymography. MMP protein and tissue ET-1 levels were evaluated by immunohistochemistry, and ET receptor density was determined by immunoblotting. Exposure to stress caused a twofold increase in plasma ET-1 levels (P < 0.05), and there was increased ET-1 staining at the tissue level. Total MMP activity and expression of MMP-2 and MMP-9 were increased in the stress group. ETA receptor antagonism prevented the increase in MMP expression and activation in the stress group. These results provide evidence that the MMP system is activated before the development of hypertension and ET-1 mediates these early events in vascular remodeling.

AB - Degradation of the extracellular matrix proteins by matrix metalloproteinases (MMP) is an important regulatory step in the vascular remodeling process. Recent studies demonstrated that ETA receptors regulate cardiac MMP activity and fibrosis in DOCA-salt hypertension. However, little is known about endothelin (ET)-1 regulation of vascular MMP activity in hypertension. Thus early changes in ET-1-mediated regulation of MMP activity were measured in borderline hypertensive rats that develop impaired vasorelaxation and hypertension with chronic exposure to stress. Experiments were performed after 10 days of exposure to the behavioral stressor, air-jet stress, but before the onset of stress-induced hypertension. Study groups were 1) control (n = 8); 2) air-jet stress for 10 days (n = 8); 3) control plus ETA antagonist ABT-627 (n = 4), and 4) air-jet stress plus ETA antagonist (n = 4). MMP activity in the thoracic aorta was assessed by gelatin zymography. MMP protein and tissue ET-1 levels were evaluated by immunohistochemistry, and ET receptor density was determined by immunoblotting. Exposure to stress caused a twofold increase in plasma ET-1 levels (P < 0.05), and there was increased ET-1 staining at the tissue level. Total MMP activity and expression of MMP-2 and MMP-9 were increased in the stress group. ETA receptor antagonism prevented the increase in MMP expression and activation in the stress group. These results provide evidence that the MMP system is activated before the development of hypertension and ET-1 mediates these early events in vascular remodeling.

KW - ABT-627

KW - Endothelin-1

UR - http://www.scopus.com/inward/record.url?scp=0142169962&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0142169962&partnerID=8YFLogxK

M3 - Article

C2 - 12842810

AN - SCOPUS:0142169962

VL - 285

SP - H2225-H2232

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 5 54-5

ER -