Figure 8.

Summary diagram of macrophage proliferation and lymphocyte infiltration in a growing atherosclerotic lesion. Upon initiation of atherosclerosis, monocytes infiltrate the endothelial layer, differentiate into macrophages, and begin to proliferate and induce lesion growth. In early lesion formation, in situ macrophage proliferation increases and more monocytes are recruited. Lesions progress as lymphocyte involvement and immune activation become prevalent. Inflammatory cell infiltrates (ICIs) comprised of proliferating lymphocytes occur concurrently as macrophages undergo apoptosis as lesions transition from the early to the intermediate stage. The exact link behind the initiation of ICI formation and apoptosis is unknown, but could involve proinflammatory signaling. Adventitial ICIs or adventitial tertiary lymphoid organs are also observed and are a potential source for lymphocyte infiltration into the intima. As the intimal ICIs resolve, proliferation slows and lesions advance to the necrotic stage containg cellular debris and cholesterol crystals.