The role of arterial wall injury in atherogenesis and arterial thrombogenesis.

Abstract

Accumulating mainly experimental evidence from research of the last 3 decades shows that many types of arterial wall injury can accelerate and intensify the development of atherosclerosis in arteries exposed to chronic hyperlipemia by increasing the permeability of their endothelium for plasma lipoproteins, proteins and several types of smooth muscle mitogens (including soluble platelet-derived growth factor). Of the numerous artery-injuring agents studied experimentally today only those that can be proven to operate in humans at concentrations and durations of action that injure animal arteries can be accepted as capable of playing a role in human atherogenesis. Seven such groups of agents can be recognized at present: blood turbulence, hypertension, certain viruses, metabolic disturbances (including hyperlipemia), certain immune insults, exogenous chemicals, and obstruction of adventitial lymphatics. Most of the above agents cause various degenerative changes in individual endothelial cells or open interendothelial junctions, and they seem to promote the penetration of plasma macromolecules into the wall in 3 different ways: directly through the altered endothelial cytoplasm, through opened interendothelial junctions or through transport in the cytoplasm of immigrating monocytes. None of the commonly occurring injury agents produce complete endothelial denudation of wide areas of the arterial cylinders. New findings from the transmission electron microscopic study of step-serial sections of human arteries obtained under conditions minimizing artificial endothelial loss indicate that endothelial denudation accompanied by platelet adherence and aggregation does not occur over early myoproliferative lesions but occasionally develops over small areas of advanced plaques with mostly necrotic or damaged caps and is, therefore, not an initiating event but a late complication of atherosclerosis. Light microscopic serial section studies of human thrombosed vessels in several centers reveal that thrombogenesis in most human atherosclerotic arteries is initiated by a severe structural injury of the cap of advanced plaques that leads to a microscopic break of the plaque surface through which some blood can enter the plaque interior before it is sealed by a thrombus.