[Why are plasmatic apoB lipoproteins atherogenic? The hypothesis of response to retention]

The development of atherosclerotic lesions can be described as a tissular response to deposition of apoB-100 containing lipoproteins (LpApoB) in the arterial intima. These particles that circulate in blood are the low-density lipoproteins (LDL), the very low and intermediate density lipoproteins (VLDL and IDL) and the Lp(a). To initiate the tissue response is critic that LpApoB are retained in the subendothelial space. This occurs by the interaction of specific positive segments of the apoB-100 with negative glycosaminoglycan chains of the proteoglycans of the intima extracellular matrix. The inflammatory response involve macrophages and other immuno-competent cells, smooth muscle cells and endothelial cells. The direct agents that induce this reaction appear to be products of hydrolytic and oxidative modifications of the phospholipids, triglycerides and sterols of the retained LpApoB. The enzymes that cause these modifications are secreted by arterial cells stimulated by pro-inflammatory cytokines. The sequence of LpApoB retention and modification in the extracellular matrix followed by proliferation and inflammation seems to be a cyclic process that leads to the chronic progress of atherosclerotic lesions. These concepts constitute the base of a new hypothesis to explain atherosclerosis: the "response to retention hypothesis".