**12. Self-progression**

Directional proportions in redistribution of injury to the vascular wall are conceptually a mechanism of a quantitatively self-progressive establishment in atherogenesis.

The murine models of atherosclerosis, particularly the transgenic models of absent ApoE gene and of absent low density lipoprotein receptor fed on a Western diet indicate the role played by lipoproteins as initiators and promoters of an essentially permissive micro-envi‐ ronment that is instrumental in atherogenesis as micro-environmental conditioning and preconditioning. In such manner, conditional remodelling of microenvironmental factors involves the characterization of many of the contributing agonists in atherogenesis. Hypoxia of the endothelium and intima is a central theme in such conditioning and allows for the multiple agonists in atherogenesis to contribute to the essential individualization of the pla‐ que within systemizing schemes of vascular wall atherosclerosis. Pathological angiogenesis enhances disease progression, increases macrophage infiltration and perpetuates necrosis and hypoxia [25].

Cellular phenotype switches are a feature affecting particularly endothelial expression of ad‐ hesion molecules and the generation of secretory roles for smooth muscle cells. P-selectins and to a lesser extent E-selectins are significant participants in adhesion of leukocytes to par‐ ticular sites in the endothelium and allow for contributions also by vascular adhesion mole‐ cules and intercellular adhesion molecules and integrins. The matrix proteoglycans significantly accumulate as a result of such phenomena that promote chemotaxis of leuko‐ cytes from flowing blood and the drawing of smooth muscle cells into the intima.

In such manner, distributional effects integrate as quantitative formulations of an atheroscler‐ otic plaque that re-characterizes dimensions of phenotype switching and formulates roles for transforming cell types. Various nuclear receptors contribute to macrophage cholesterol me‐ tabolism, which in turn keeps the arteries in a chronically inflamed state [26].
