Biomarkers for cobalt cardiotoxicity
Research type
Research Study
Full title
Investigating the translational application of calcium/calmodulin protein kinase II as a biomarker for cobalt cardiotoxicity
IRAS ID
258866
Contact name
Susan Currie
Contact email
Sponsor organisation
University of Strathclyde
Duration of Study in the UK
1 years, 11 months, 31 days
Research summary
There is very strong evidence supporting a link between hip replacements (where metals such as cobalt and chromium are used in the artificial joint bearings) and heart disease. Over time, cobalt levels rise in the bloodstream of patients and levels accumulating in the heart can be particularly high. Left untreated, this can lead to heart failure. One of the biggest problems for clinicians treating hip replacement patients is that they cannot tell whether or when patients will develop heart disease. Currently there is nothing they can measure that allows them to predict patient outcome. We have shown that cobalt treatment of rats causes impaired cardiac contractility and abnormal heart cell function. From previous extensive work in animals models we know that the levels and activity of a particular cardiac protein (CaMKIIdelta) are dramatically altered early on in heart disease, often before any significant functional effects are observed. CaMKIIdelta and related responsive and gene-regulating microRNAs could therefore prove to be novel 'biomarkers' that we could use to assess changes happening inside cells before dysfunction is evident at the level of the heart. This project will be conducted over two years in SIPBS. Initial 'proof of concept' work using artificial proteins and primary cardiac cells will aim to show that cobalt can alter CaMKII activity. We will then demonstrate that by selectively inhibiting CaMKIIdelta in the whole animal (rat), we can reduce/reverse the effects of cobalt on the heart. Once the animal findings are confirmed, we will in the latter six months of the project, examine blood samples from hip replacement patients. We anticipate that specific CaMKIIdelta biomarkers will be changed in at least a cohort of these patients. The findings will provide new information for clinicians on how to more accurately predict whether hip replacement patients will develop heart disease.
REC name
London - Hampstead Research Ethics Committee
REC reference
19/LO/0539
Date of REC Opinion
26 Apr 2019
REC opinion
Further Information Favourable Opinion