Endothelial Progenitor Cells: New Targets to Control Autoimmune Disorders

Abstract

The formation of blood vessels is essential for preparing a closed circulatory system in the body, and for supply of oxygen and nutrients to all tissues and organs. One of the key mechanisms behind many autoimmune diseases is abnormal blood vessel structure and function. This dysfunction is reflected in some of the serious manifestations of rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM) and systemic sclerosis (SSc) that are currently difficult to treat, such as loss of fingers due to reduced blood flow, kidney failure due to renal hypertensive crisis and heart failure due to pulmonary arterial hypertension. The cells that line blood vessels (endothelial cells) not only confine blood to the vessels but actively participate in the recruitment of circulating cell subsets to sites of inflammation and vascular permeability for the exchange of solutes and gases. Collectively, endothelial cells play many roles in the development and maintenance of blood vessels. Blood vessel development occurs primarily via one of two mechanisms, angiogenesis (the generation of blood vessels from pre-existing vasculature) and vasculogenesis (the recruitment of endothelial progenitor cells from the bone marrow to sites of vascularisation). In recent decades, extensive studies have revealed that a variety of factors and their receptors regulate angiogenesis in vertebrates, including vascular endothelial growth factor (VEGF)-VEGFRs, angiopoietin-Tie, Ephrins-EphRs and Delta-Notch (reviewed by Karamysheva (Karamysheva, 2008)). Indeed, targeting these molecules has resulted in significant advances in the treatment of cancer and cardiovascular disease. However, the burden of diseases that involve vascular dysfunction is immense and continues to rise with drug resistance, intolerance and ineffectiveness being significant contributors. Less is known about the mechanisms underpinning vasculogenesis and despite an explosion of research in this area over the past decade we are yet to fully exploit these cells for therapeutic benefit (Sen et al., 2011, Sieveking and Ng, 2009). This chapter discusses whether the endothelial progenitor cells (EPCs) from patients with autoimmune diseases, such as RA, T1DM and SSc, behave differently from normal EPCs and whether there are factors in the serum of these patients that may be responsible for this abnormal behaviour. The altered behaviour of EPCs in patients with autoimmune disease is poorly understood, based on limited studies to date. This chapter addresses whether EPCs would be a prime target for therapeutic intervention in the serious complications of autoimmune disease.