Investigating the cardiotoxic effects of cobalt on adult human female cardiac fibroblasts

Cardiotoxicity is a leading cause of drug and device withdrawal from the market and is a major area of focus for safety screening in the pharmaceutical industry as well as in the clinic. Improved technologies for assessing cardiotoxicity using human cells that mimic the heart microenvironment are therefore needed. Within our laboratory we are investigating the impact that circulating cobalt ions (released from metal-on-metal implants in patients with hip replacements) may have on cardiac function. Previous work in our laboratory has examined the impact of cobalt in vivo in an animal model and has shown evidence for cardiac remodelling and diastolic dysfunction. The underlying cardiotoxic mechanism of action of cobalt at a cellular level remains unknown.
This Vacation project will focus on characterisation and physiological responses of human ventricular cardiac fibroblasts (CFs) to cobalt. The project will examine the effects of cobalt on CF phenotype, collagen production and proliferation in both male and female cells derived from healthy human subjects. Key aims will include investigating whether cobalt may cause (i) phenotypic switching of CFs towards a muscle-like phenotype and (ii) evidence of fibrotic, apoptotic or inflammatory signalling. The project will encompass a range of techniques including primary cell culture, imaging, immunocytochemistry and immunoblotting. Should time permit, we may also monitor changes in intracellular calcium responses following cobalt application. Awarded £2,646