Potential role of endothelin 1 in ischaemia-induced angiogenesis in critical leg ischaemia.
BACKGROUND
Ischaemia-induced angiogenesis occurs in critical leg ischaemia (CLI) and endothelin (ET) 1 may be involved in this process. The aim of this study was to quantify microvessels and study ET receptor expression and distribution in critically ischaemic leg muscle.


METHODS
Leg muscle biopsies were taken from 12 patients with CLI and 12 patients with no leg ischaemia. Microvessels were identified immunohistochemically on muscle sections, and the number of immunopositive cells was quantified. ETA and ETB receptor messenger RNA (mRNA) expression was studied using real-time quantitative reverse transcriptase-polymerase chain reaction, and receptor binding was localized and assessed by in vitro autoradiography.


RESULTS
The number of microvessels in CLI muscle biopsies was 2.6 times higher than that in controls (P < 0.01). ETB receptor mRNA expression and binding were significantly increased in CLI tissue (P < 0.05), while ETA receptor levels were not significantly raised. High-resolution autoradiography showed that ET receptor binding was associated with microvessels.


CONCLUSIONS
Angiogenesis occurs in CLI and raised ETB receptors within the muscle were associated with microvessels, suggesting that ET-1 may mediate angiogenesis via these receptors in critically ischaemic muscle.
Tsui
J C S
JC
Department of Surgery, Royal Free and University College Medical School, Royal Free Campus, Pond Street, London NW3 2QG, UK. jcstsui@hotmail.com
Baker
D M
DM
Biecker
E
E
Shaw
S
S
Dashwood
M R
MR
D000368:Aged; D000369:Aged, 80 and over; D001345:Autoradiography; D001706:Biopsy / Q000379:methods; D019332:Endothelin-1 / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D007866:Leg / Q000098:blood supply*; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000209:etiology*; D017466:Receptors, Endothelin / Q000378:metabolism*
D019332:Endothelin-1; D017466:Receptors, Endothelin