Rheumatoid arthritis (RA) is a chronic and progressive inflammatory disease of the joints characterized by synovial inflammation and destruction of cartilage and bone. There is increasing awareness that RA is not only limited to the local joint inflammatory state. Of emerging significance is the relationship between RA and systemic inflammation which increases damage to cardiac and endothelial cells. This is coupled with impaired heart and vascular functions, thus contributing to the risk of cardiovascular disease (CVD). Subsequently, CVD is the main cause of the excess morbidity and mortality risk as RA patients may have cardiac problems within one year following diagnosis. Moreover, the risk of having a heart attack and other forms of coronary heart disease increases by 60% in one to four years after the RA diagnosis. Although this recognition has been described by clinicians, the exact reason for the increased CV risk in RA patients is still under intense study. In addition, a novel biological medication used to treat RA may modulate CV risk, therefore should be addressed in cardiovascular drug toxicity. For this reason, the main objective of this project was to generate a novel cellular tool that may help to identify more specific molecular mechanisms associated with the development of heart complications in RA patients.
To date, most of the RA research has been traditionally based on a variety of in vitro assays and animal models which may not entirely recapitulate extra-articular manifestations and drug responses. In turn, human cardiomyocytes are difficult to access from the heart of RA patients. Therefore, in this project, we implemented the modern technology of induced pluripotent stem cells (iPSC), pioneered by Shinya Yamanaka’s lab in Kyoto, Japan, who was awarded the 2012 Nobel Prize. iPSCs are a type of stem cell that can be generated directly from adult cells like fibroblasts or blood cells. iPSCs have the same properties as embryonic stem cells, i.e. self-renewing and pluripotent differentiation giving rise to many other cell types, such as neurons, heart, pancreatic, and liver cells. Therefore, nowadays iPSCs have become an important tool for modeling and investigating many human diseases, for screening drugs, and in the field of regenerative medicine.
