Figure 1.

Pathogenetic links between systemic and cardiovascular inflammation. Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1), upregulated in the setting of systemic inflammation, trigger endothelial activation. The ensuing overexpression of endothelial leukocyte adhesion molecules leads to increased recruitment and activation of inflammatory cells within the arterial wall, resulting in destabilization of endothelial hemostasis, endothelial dysfunction and vascular inflammation. The heightened synthesis of potent procoagulant molecule tissue factors by activated endothelial cells induces platelet adhesion and aggregation, creating a prothrombotic state. Moreover, systemic inflammation associates with an increase in oxidized low-density lipoprotein (LDL-ox) particles along with a reduction in high-density lipoprotein (HDL). These inflammation-driven mechanisms are responsible for the derangement of vascular architecture which represents the earliest step of atherosclerosis, ultimately resulting in vulnerable plaque formation and rupture.