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Increased expression of vascular endothelin type B and angiotensin type 1 receptors in patients with ischemic heart disease

Dimitrijevic, Ivan LU ; Edvinsson, Marie-Louise; Chen, Qingwen LU ; Malmsjö, Malin LU ; Kimblad, Per Ola LU and Edvinsson, Lars LU (2009) In BMC Cardiovascular Disorders 9.
Abstract
Background: Endothelin-1 and angiotensin II are strong vasoconstrictors. Patients with ischemic heart disease have elevated plasma levels of endothelin-1 and angiotensin II and show increased vascular tone. The aim of the present study was to examine the endothelin and angiotensin II receptor expression in subcutaneous arteries from patients with different degrees of ischemic heart disease. Methods: Subcutaneous arteries were obtained, by biopsy from the abdomen, from patients undergoing coronary artery bypass graft (CABG) surgery because of ischemic heart disease (n = 15), patients with angina pectoris without established myocardial infarction (n = 15) and matched cardiovascular healthy controls (n = 15). Endothelin type A ( ETA) and type... (More)
Background: Endothelin-1 and angiotensin II are strong vasoconstrictors. Patients with ischemic heart disease have elevated plasma levels of endothelin-1 and angiotensin II and show increased vascular tone. The aim of the present study was to examine the endothelin and angiotensin II receptor expression in subcutaneous arteries from patients with different degrees of ischemic heart disease. Methods: Subcutaneous arteries were obtained, by biopsy from the abdomen, from patients undergoing coronary artery bypass graft (CABG) surgery because of ischemic heart disease (n = 15), patients with angina pectoris without established myocardial infarction (n = 15) and matched cardiovascular healthy controls (n = 15). Endothelin type A ( ETA) and type B (ETB), and angiotensin type 1 (AT(1)) and type 2 (AT(2)) receptors expression and function were examined using immunohistochemistry, Western blot and in vitro pharmacology. Results: ETA and, to a lesser extent, ETB receptor staining was observed in the healthy vascular smooth muscle cells. The level of ETB receptor expression was higher in patients undergoing CABG surgery (250% +/- 23%; P < 0.05) and in the patients with angina pectoris (199% +/- 6%; P < 0.05), than in the healthy controls (100% +/- 28%). The data was confirmed by Western blotting. Arteries from CABG patients showed increased vasoconstriction upon administration of the selective ETB receptor agonist sarafotoxin S6c, compared to healthy controls (P < 0.05). No such difference was found for the ETA receptors. AT(1) and, to a lesser extent, AT(2) receptor immunostaining was seen in the vascular smooth muscle cells. The level of AT(1) receptor expression was higher in both the angina pectoris (128% +/- 25%; P < 0.05) and in the CABG patients (203% +/- 41%; P < 0.05), as compared to the healthy controls (100% +/- 25%). The increased AT(1) receptor expression was confirmed by Western blotting. Myograph experiment did however not show any change in vasoconstriction to angiotensin II in CABG patients compared to healthy controls (P = n.s). Conclusion: The results demonstrate, for the first time, upregulation of ETB and AT(1) receptors in vascular smooth muscle cells in ischemic heart disease. These receptors may play a role in the pathophysiology of ischemic heart disease and could provide important targets for pharmaceutical interventions. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
BMC Cardiovascular Disorders
volume
9
publisher
BioMed Central
external identifiers
  • wos:000270296300001
  • scopus:70349329422
ISSN
1471-2261
DOI
10.1186/1471-2261-9-40
language
English
LU publication?
yes
id
d8ed4720-294c-4439-80aa-6c02957786cc (old id 1489788)
date added to LUP
2009-10-21 12:02:01
date last changed
2017-12-10 04:08:44
@article{d8ed4720-294c-4439-80aa-6c02957786cc,
  abstract     = {Background: Endothelin-1 and angiotensin II are strong vasoconstrictors. Patients with ischemic heart disease have elevated plasma levels of endothelin-1 and angiotensin II and show increased vascular tone. The aim of the present study was to examine the endothelin and angiotensin II receptor expression in subcutaneous arteries from patients with different degrees of ischemic heart disease. Methods: Subcutaneous arteries were obtained, by biopsy from the abdomen, from patients undergoing coronary artery bypass graft (CABG) surgery because of ischemic heart disease (n = 15), patients with angina pectoris without established myocardial infarction (n = 15) and matched cardiovascular healthy controls (n = 15). Endothelin type A ( ETA) and type B (ETB), and angiotensin type 1 (AT(1)) and type 2 (AT(2)) receptors expression and function were examined using immunohistochemistry, Western blot and in vitro pharmacology. Results: ETA and, to a lesser extent, ETB receptor staining was observed in the healthy vascular smooth muscle cells. The level of ETB receptor expression was higher in patients undergoing CABG surgery (250% +/- 23%; P &lt; 0.05) and in the patients with angina pectoris (199% +/- 6%; P &lt; 0.05), than in the healthy controls (100% +/- 28%). The data was confirmed by Western blotting. Arteries from CABG patients showed increased vasoconstriction upon administration of the selective ETB receptor agonist sarafotoxin S6c, compared to healthy controls (P &lt; 0.05). No such difference was found for the ETA receptors. AT(1) and, to a lesser extent, AT(2) receptor immunostaining was seen in the vascular smooth muscle cells. The level of AT(1) receptor expression was higher in both the angina pectoris (128% +/- 25%; P &lt; 0.05) and in the CABG patients (203% +/- 41%; P &lt; 0.05), as compared to the healthy controls (100% +/- 25%). The increased AT(1) receptor expression was confirmed by Western blotting. Myograph experiment did however not show any change in vasoconstriction to angiotensin II in CABG patients compared to healthy controls (P = n.s). Conclusion: The results demonstrate, for the first time, upregulation of ETB and AT(1) receptors in vascular smooth muscle cells in ischemic heart disease. These receptors may play a role in the pathophysiology of ischemic heart disease and could provide important targets for pharmaceutical interventions.},
  author       = {Dimitrijevic, Ivan and Edvinsson, Marie-Louise and Chen, Qingwen and Malmsjö, Malin and Kimblad, Per Ola and Edvinsson, Lars},
  issn         = {1471-2261},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {BMC Cardiovascular Disorders},
  title        = {Increased expression of vascular endothelin type B and angiotensin type 1 receptors in patients with ischemic heart disease},
  url          = {http://dx.doi.org/10.1186/1471-2261-9-40},
  volume       = {9},
  year         = {2009},
}