Inflammation and cardiovascular diseases

The causal role of inflammation at the core of endothelial dysfunction, atherosclerosis and cardiovascular diseases is discussed. Atherosclerosis is an arterial disease characterized by subendothelial accumulation of oxidized lipoproteins, vascular wall cells, blood cells, cells of the immune response, an extracellular matrix, and apoptotic cells or debris. Inflammation drives atherogenesis and the mechanisms of complications of this disease. The oxidized lipoproteins acquire features of damage-associated molecular patterns that trigger inflammatory procedures as an innate immune response, dominated by platelets and leucocytes. Although lipid risk factors such as low-density lipoprotein (LDL) likely play a permissive role in human atherogenesis, other diseases and their associated triggers of inflammation may aggravate atherosclerotic risk. Thus, even though there is a clear mechanistic link between hyperlipidemia and atherogenesis, a growing body of research indicates that cellular immune factors and cells associated with chronic inflammation can also promote atherogenesis independent of hyperlipidemia. When unresolved, these inflammatory responses become chronic, leading to further oxidative damage of plasma-lipoproteins that culminates with the inappropriate recruitment of platelets and several leukocyte subtypes at the vascular wall, which affects endothelial activation and permeability. This cycle of events can lead to endothelial dysfunction as well as the migration of monocytes that differentiate to macrophages and eventually develop into foam cells. These macrophages continuously accumulate oxLDL. However, defective clearance of apoptotic cells and debris leads to the development of plaque. As the plaque continues to develop, it can become unstable and rupture, leading to arterial damage and thrombosis. This chapter addresses the evidence surrounding the mechanistic cross-talk of inflammatory mediators and signaling pathways between blood cells and endothelial cells.