Cardiovascular Complications of Obesity in Humans

The incidence of obesity in children and adults is rising and is a major health problem that is reaching epidemic proportions. Obesity increases the likelihood of developing a range of chronic diseases (e.g. type 2 diabetes, some cancers, osteoarthritis) and there is now a well established link between increased body mass index and disorders of the cardiovascular system, including coronary artery disease and hypertension. Cardiovascular homeostasis is critically dependent upon proper functioning of the vascular endothelium which expresses and/or releases a range of proteins/mediators in response to circulating or locally- produced stimuli in a tissue-specific manner. In unperturbed blood vessels the balance of expression of these molecules by endothelial cells ensures that an anti-inflammatory and anti- thrombotic state prevails under these conditions. Pathology tips this balance to favour inflammation and thrombosis, resulting in a complex condition known as endothelial dysfunction which precedes the development of vascular disorders, including atherosclerosis. Endothelial dysfunction can be triggered by chronic exposure to a range of circulating factors, with oxidised lipoproteins and pro-inflammatory cytokines (e.g. MCP-1, TNFα, IL-6) the most well studied. Through a number of complex intracellular signalling mechanisms these mediators stimulate increased adhesion molecule expression by endothelium, encouraging chemotaxis, adhesion and trans-endothelial migration of leucocyte subpopulations, and concomitantly suppress the release of other mediators (e.g. nitric oxide) that normally protect the vessel wall by actively limiting these events. [...]