Effects of PTP1B inhibition on macrophage activity in atherosclerosis
Research type
Research Study
Full title
PTP1B inhibition in high-risk patients as a new tool for the treatment of atherosclerosis: in vitro proof of concept
IRAS ID
232029
Contact name
Oliver Helk
Contact email
Sponsor organisation
University of Aberdeen and NHS Grampian
Clinicaltrials.gov Identifier
Research Registry, researchregistry3235
Duration of Study in the UK
1 years, 0 months, 4 days
Research summary
The deposition of lipids and accumulation of inflammatory cells in arterial walls, a process called atherosclerosis, is the underlying mechanisms of myocardial infarction and the most common forms of heart disease. Existing therapies are aimed at lowering blood lipids and thus far, no drug that modulates the equally important macrophage-driven inflammatory response is available.
The aim of our project is to provide first evidence from cell culture that Trodusquemine, a selective inhibitor of PTP1B, is able to improve the inflammatory profile of macrophages when exposed to inflammatory stimuli that mimic the conditions that can be found in atherosclerosis. PTP1B was previously shown to be of crucial importance to inflammation and atherosclerosis in mice.
To assess the role of PTP1B we aim to collect blood from patients suffering from ischaemic heart disease with and without diabetes, isolate their monocytes/macrophages and compare the response of these cells to cells obtained from healthy volunteers. In a first step, PTP1B levels will be compared between the three groups to confirm our hypothesis that PTP1B is increased in atherosclerosis. In a second step, macrophages will be exposed to Trodusquemine, with the aim of lowering PTP1B activity and possibly gene expression. In a third step, we wish to confirm that the reduction of PTP1B activity by Trodusquemine has beneficial effects to inflammatory response to various pro-inflammatory stimuli that can also be found in atherosclerotic vessels.
The goal of this study is to provide evidence for future clinical trials and thus to aid the development of a new targeted approach to combat atherosclerosis and heart disease.REC name
East Midlands - Leicester Central Research Ethics Committee
REC reference
17/EM/0454
Date of REC Opinion
5 Dec 2017
REC opinion
Favourable Opinion