Hypoxia as a Factor Involved in the Regulation of the apoA-1, ABCA1, and Complement C3 Gene Expression in Human Macrophages (original) (raw)

Atherosclerosis is a chronic inflammatory disease associated with the formation of plaques in the arterial tunica intima. It is developed mainly in distorted arteries under hemodynamic shear stress [1]. Shear stress can be caused by a laminar or disturbed blood flow, with the lat ter leading to vessel damage and subsequent endothelium activation and thickening of tunica media and intima. Endotheliocytes trigger expression of adhesive agents, integrins, selectins, interleukins, interferons, and cytokines. Concurrent increase of vessel permeability leads to infiltration of the subendothelial space by low density lipoproteins (LDL). These molecules are bound in the intima by proteoglycans of the extracellular matrix and undergo various modifications like oxidation, prote olysis, etc. Modified LDL are absorbed by macrophages engaged during endothelium activation, which induces accumulation of intracellular cholesterol and leads to transformation of macrophages into foam cells [2]. Attraction of monocytes and thickening of intima by proliferation of smooth muscle cells leads to growth of atherosclerotic plaques and sparseness of capillaries that nourish the artery middle coat. An increased demand for oxygen triggers vascularization of the intima and plaque, but new vessels tend to originate at the perimeter of the plaque, with its center remaining under permanent hypoxia [3].