Atherosclerosis: integration of its pathogenesis as a self-perpetuating propagating inflammation: a review

This review proposes that the development of the atherosclerotic plaque is critically dependent on its inflammatory components forming a self-perpetuating and propagating positive feedback loop. The components involved are: (1) LDL oxidation, (2) activation of the endothelium, (3) recruitment of inflammatory monocytes, (4) macrophage accumulation, which induces LDL oxidation, and (5) macrophage generation of inflammatory mediators, which also activate the endothelium. Through these stages, the positive feedback loop is formed, which generates and promotes expansion of the atherosclerotic process. To illustrate this dynamic of lesion development, the author previously produced a computer simulation, which allowed realistic modelling. This hypothesis on atherogenesis can explain the existence and characteristic focal morphology of the atherosclerotic plaque. Each of the components contributing to the feedback loop is discussed. Many of these components also contain subsidiary positive feedback loops, which could exacerbate the overall process.