**9. Nonresolution**

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, oxidative stress and protease activity [36].

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 instability as plaque rupture.

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‐ ed with overlapping risk factors [8]. The overall dimensions of plaque evolution are hence highly complex, and such complexity is largely attributable to participants from the overly‐ ing luminally disturbed blood flow.

In spite of such considerations an essential role for hypoxia specifically affects the endotheli‐ um and other components of the vascular wall.
