ApoE proteoform analysis in tissues from amputated limbs.
Research type
Research Study
Full title
Analysis of ApoE proteoforms in tissue samples collected from individuals undergoing lower limb amputation.
IRAS ID
246791
Contact name
David Mosedale
Contact email
Clinicaltrials.gov Identifier
researchregistry4343, Research Registry
Duration of Study in the UK
10 years, 2 months, 31 days
Research summary
The primary objective of the study is to analyse proteoforms of apolipoprotein E in different tissues from a number of individuals. Different forms of proteins can be generated as a result of genotype. However, even individuals with exactly the same genotype can have different proteoforms of a protein due to errors in transcription or translation, or due to different post translational modification(s), folding or degradation. It is hypothesised these processes may result in differences in different tissues within the same individual, especially if the modification(s) result in different proteoforms trafficking to different compartments, or making an insoluble proteoform.
Methuselah Health UK (MHUK) have developed a method to analyse proteoforms of ApoE by using LC-MS/MS analysis of signature peptides. This study is aimed at analysing proteoforms of ApoE in the blood with ApoE in the wall of the blood vessel (which may be intracellular or, if in an atherosclerotic plaque, insoluble).
Peripheral vascular disease is a narrowing of blood vessels, usually due to atherosclerosis. This most commonly affects diabetics and in its most severe forms can lead to amputation of the lower limb due to development of necrosis and/or gangrene. In collaboration with the vascular surgery team at Addenbrooke’s Hospital, MHUK would like to obtain tissues dissected from a small number of amputated lower limbs as well as a sample of blood. Most of the amputees are likely to be diabetics however other amputees will not be excluded. Proteoforms of ApoE in the blood vessel wall will be compared to those in the blood itself. Collection of other tissues (skin, nerve and muscle) will permit investigations into ApoE proteoforms in other tissues. In addition, methods may be developed to analyse peptide signatures of the proteoforms of other proteins which may be of interest and the tissues will be used for analysis of these.
REC name
East of England - Cambridge Central Research Ethics Committee
REC reference
18/EE/0308
Date of REC Opinion
4 Dec 2018
REC opinion
Further Information Favourable Opinion