VASGBI Project Grant

The successful applicant for the VASGBI Project Grant was:

Principal Applicant
Professor Dave Lambert
University of Leicester

Effects of opioids on angiogenesis


Scientific Abstract
Perioperative opioid use has a negative impact on outcome from cancer surgery. In terms of tumour survival increased migration/proliferation, immune suppression and angiogenesis are all predicted to worsen patient outcome. Opioid receptors have been reported on tumour cells where they increase migration; opioids are immunodepressant and stimulate angiogenesis. In essence perioperative opioids in cancer surgery represents 'the perfect storm'. The aim of this application is to examine the effects of opioid receptor activation on (i) vascular endothelial
and smooth muscle cell function in vitro and (ii)aneurysm and microvascular involvement in an in vivo mouse model. Our hypothesis is that opioids will increases angiogenesis and there will be differences among the four opioid receptor subtypes. In vitro we will use standard laboratory techniques to measure opioid receptor mRNA transcripts and function (proliferation/migration). What is particularly novel is the use of the ApoE-/- hypercholesterolaemic mouse treated with Angiotensin-II to induce aneurysm formation associated with extensive angiogenesis; along with the systematic use of ligands for all opioid receptor subtypes. If there are differences in the angiogenic profiles then this will strengthen the logic for generation of analgesics with targets beyond the receptor for morphine or use of peripherally restricted opioid antagonists in cancer surgery.

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