**10. Neovascularization**

endothelial cells [14]. The proximity of the tunica intima to both overlying endothelium and to tunica media promotes the interactivity of smooth muscle cells within paracrine and auto‐ crine systems of determining pathobiology. The significance attributed to such pathways as deposition of proteoglycan matrix within the intima proves a heterogeneity of involvement as significant characterization of multiple forms of progression of the individual atheroscler‐ otic plaque. In such manner, distributional dynamics within foci of involvement by athero‐ sclerosis allow for the emergence of parameters of progression that identifiably further promote permissive conditions of a quantitative nature in accumulation and chemotaxis of

The complicated atherosclerotic plaque shows an essential neovascular component at its base and this appears to be a primary source for the establishment of complications such as intra-plaque hemorrhage and for rupture of the lipid core of the plaque into the vascular lu‐ men. It is in terms of ongoing proliferation of a phenotypically secretory smooth muscle cell population that enlargement of the individual plaque proves self-progressive in dimensions and also self-progressive in terms of transforming dynamics to the complicated or ruptured plaque. In such manner, the overall contribution of injury to the overlying endothelium con‐ firms dimensions of non-resolution beyond the fatty streak stage. Inflammasomes regulate proinflammatory caspases and interleukin-1 cytokines in response to various stimuli [24].

Integral participation of multiple foci of injury to a given point in vascular wall atherogene‐ sis hence proves an inbuilt progression that is quantitatively determined but that allows a permissive microenvironment to promote transformability to the unstable plaque. It appears significant to view the unstable plaque as a transforming event in its own right beyond the dimensions of any individual atherosclerotic lesion. It is in such a setting that neovasculariza‐ tion of the plaque is a central agonist in the creation of acute coronary events as seen clinically.

The proinflammatory attributes of the atherosclerotic plaque accompany the dynamics of the neovascularization phenomenon in promoting the emergence of a permissive micro-en‐ vironment within the vascular wall. Macrophages phagocytose apoptotic cells, clear necrotic debris and repair tissues; these are challenged by local cell stressors that include hypoxia,

The intimal remodelling is, in part, an expression of such pro-inflammatory activity. Im‐ mune responses to plaque antigens modulate inflammatory responses in the intima [39]. It is in terms of ongoing participation of new agonists that the atherogenesis proves a promo‐ tional agonist in its own right in determining the dynamics of vascular stenosis and also of

Thrombosis overlying the atherosclerotic plaque is a phenomenon as complicated plaque emergence and is believed to be a direct contributor to the establishment of further compli‐ cations in clinically unstable angina. Venous and arterial thromboses are probably associat‐

monocytes in particular.

242 Current Trends in Atherogenesis

**9. Nonresolution**

oxidative stress and protease activity [36].

instability as plaque rupture.

The neovascularization at the base of the complicated atherosclerotic plaque may be an ex‐ pression of such overall effects of hypoxia that transforms accumulative phenomena of athe‐ rogenesis as complicated plaques that rupture into the lumen.

The pro-inflammatory nature of plaques appears also expressive parameter of such hypoxia as a result of a neovascularity that further emerges as an over-riding phenomenon of per‐ missiveness in atherogenesis. In this regard Nuclear Factor-kappaB plays an orchestrating role in formulating multiple heterogeneous elements in evolutionary permissiveness. As HIV infected patients age, atherosclerosis has become an increasing cause of morbidity and mortality, initiating immune and inflammatory responses [23].

The directional promotion in development of the unstable plaque is therefore an expression of transformational dynamics that promotes the rupture of the overlying fibrous cap and the extrusion of the lipid core. The biophysics of such fibrous cap appears instrumental particu‐ larly in the disruption of the junctional elements with the adjacent vascular wall.

The interplay of genetic factors with micro-environmental agonists is particularly significant in terms of the dynamics of lipid accumulation within the plaque [16].

Such phenomenal increments play contributing roles of the overlying blood flow in redis‐ tributing lipoproteins and cholesterol within the vascular wall. The dimensions of the lipid core are themselves determining agonists in plaque rupture, and a high content of such lipid core to over 40% of the overall plaque is significant in this regard.

Redistribution of attributes within the individual atherosclerotic plaque appears a promo‐ tional feature as pro-inflammatory effects and as plaque neovasculature. The hypoxic envi‐ ronment would account for permissive emergence of multi-component parameters that coordinate the characterization of the final complicated atherosclerotic plaque within di‐ mensions of accumulation of lipid and transformation to plaque rupture.
