Effect of endothelial and adventitial injury on somatostatin receptor expression

doi:10.1067/msy.2000.105027

Surgery

Volume 127, Issue 5, May 2000, Pages 577-583

Presented in part at the 5^th Annual Western Resident's Forum, Whistler, BC, September 13, 1998.

https://doi.org/10.1067/msy.2000.105027 Get rights and content

Abstract

Background. The somatostatin analog, angiopeptin, inhibits intimal hyperplasia formation; although the specific somatostatin receptor (SSTR) subtypes transducing this effect are unknown. The purpose of this study was to determine the expression of SSTR subtypes in rat iliac arteries after balloon catheter endothelial injury and perivascular dissection. Methods. Male rats received balloon endothelial injury to their left common and external iliac arteries with or without circumferential arterial dissection. The right arteries served as controls. At 1 and 2 months after intimal injury, animals were killed and their iliac arteries harvested and studied for SSTR expression by using immunocytochemical and molecular techniques. Quantitative polymerase chain reaction was used to determine the level of SSTR expression. Results. Normal rat iliac arteries expressed only SSTR2 and 3. After balloon endothelial injury, there was significant upregulation of SSTR2 messenger RNA at 1 and 2 months after injury as compared with controls (1 month, 1.8 ± 0.3 vs 0.4 ± 0.1 zmol, P <.001; 2 months, 2.7 ± 0.5 vs 1.1 ± 0.2 zmol, P <.001). The addition of adventitial dissection to endothelial injury also showed a significant increase in SSTR2 expression (1 month, 2.4 ± 0.4 vs 0.8 ± 0.2, P <.05; 2 months, 1.3 ± 0.3 vs 0.7 ± 0.3, P <.05), but not significantly greater than that seen after balloon endothelial injury alone. Immunocyto-chemical studies also demonstrated an increase in SSTR2 immunoreactivity on the luminal surface of the endothelial cells in the balloon catheter-injured arteries. Conclusions. These findings show that SSTR2 is the primary SSTR that is upregulated after injury and likely mediates the effects of somatostatin analogs on intimal hyperplasia. (Surgery 2000;127:577–83.)

Section snippets

Animals

Wistar rats weighing 400 to 500 g were obtained from the Animal Care Facility at the University of British Columbia and housed in a 12-hour light/dark cycle. All animal procedures were approved by the University of British Columbia Animal Care Committee, and animals were cared for in accordance with the principles contained in The Care of Experimental Animals - A Guide for Canada, published by the Canadian Council on Animal Care (1993).

Rats were anesthetized with intravenous pento-barbital and

Immunocytochemistry

Immunocytochemical staining of normal arterial samples with antibodies to SSTR1, SSTR2, and SSTR3 failed to show any significant level of immunoreactivity. The antibody to SSTR2 occasionally showed punctate staining of the surface of endothelial cells but this was barely above background levels. However, in the balloon catheter injured and dissected arteries, or dissected arteries alone, there was a clear increase in SSTR2 immunoreactivity on the endothelial cells (Fig 1, A and B).

Discussion

Previous studies using SST analogs known to activate members of the SSTR2, 3, and 5 subgroups have been successful in limiting intimal hyperplasia after vascular injury.4, 6, 10, 15, 16 However, the precise SST receptor subtype activated after injury to blood vessels has not been determined. The results of this study demonstrate that SSTR2 and 3 are present in the normal rat iliac artery and, in response to either endothelial or endothelial and adventitial injury, SSTR2 is significantly

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^*: Funded in part by the Heart and Stroke Foundation of British Columbia and Yukon and the Rogers Research Foundation.

^**: Reprint requests: Dr York N. Hsiang, Division of Vascular Surgery, Department of Surgery, University of British Columbia, Vancouver General Hospital, Room 3100 LSP, 910 W 10th Ave, Vancouver, BC, V5Z 4E3, Canada.

^★: Surgery 2000;127:577–83

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Original CommunicationsEffect of endothelial and adventitial injury on somatostatin receptor expression*,**,★

Abstract

Section snippets

Animals

Immunocytochemistry

Discussion

Atherosclerosis

Atherosclerosis

Am Heart J

Transplant Proc

Metabolism

Eur J Pharmacol

Incidence of restenosis after successful coronary angioplasty: a time-related phenomenon

J Am Coll Cardiol

Restenosis after coronary angioplasty: an overview

J Am Coll Cardiol

Restenosis after successful coronary angioplasty

N Engl J Med

Peptide inhibition of myointimal proliferation following angioplasty in rabbits

Transpl Proc

Original Communications
Effect of endothelial and adventitial injury on somatostatin receptor expression*,**,★