Modified Response to Injury Hypothesis of Atherosclerosis Development

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The Modified Response to Injury Hypothesis of Atherosclerosis Development

The modified response to injury hypothesis, as it pertains to the development of atherosclerosis, proposes the following tenets: (1) endothelial injury results in growth factor secretion; (2) the local hemodynamic environment (low shear and oscillating shear) facilitates local injury and particle transfer; (3) circulating monocytes attach to the damaged endothelium; (4) subendothelial migration of monocytes may lead to fatty streak formation and further release of growth factors such as PDGF; (5) fatty streaks may then be converted to fibrous plaques via release of growth factors from macrophages, endothelial cells, or both; (6) macrophages may stimulate or injure the overlying endothelium, thus endothelial cell loss leads to platelet deposition; (7) platelet deposition leads to the release of growth factors and mitogenic factors for smooth muscle cells; and ( 8
) some of the smooth muscle cells in the proliferative lesion itself may form and secrete growth factors.