Significance of Thrombus Formation and Infiltration of Plasma Proteins as Initiating Factors in Atherogenesis

Abstract

There is a controversial problem what changes in the arterial intima are truly precursors of atheroma. Prior to the development of atheroma, varying degrees of fibrous thickening usually exist in the intima. Some investigators suggest that such intimal proliferative changes are the result of a physiological ageing process, but in my opinion, they are an integral part of the atherosclerotic process and “preatheromatous lesions”, because the degree of such changes displays wide variations from case to case in relation to age, thus it seems unlikely that age per se accounts for them.
The purpose of this report is to discuss the significance of thrombus formation and infiltration of plasma proteins, particularly of fibrinogen (fibrin) and β-lipoprotein, into the arterial walls in the development of “preatheromatous lesions” and atherosclerosis.
1. A preatheromatous lesion is derived from the organization of the mural thrombus.
The mural white thrombus on the aorta of rabbits induced by insertion of polyethylene tubing was subsequently organized by modified smooth muscle cells and incorporated into the aortic wall, resulting in the fibrous thickening of the intima, “preatheromatous lesion”. Some of these lesions further became the atherosclerotic lesions resembling those found in man, without any cholesterol feeding.
The endothelial damage and direct exposure of the subendothelial materials, mainly of microfibrils and collagen, were apparently necessary for the initiation of in vivo mural thrombus in the aorta.
2. Plasma proteins, fibrinogen and β-lipoprotein, might pass through the aortic and large and medium-sized arterial walls of human. The endothelium and the elastic membrane of the arterial wall might act as a barrier to the passage of plasma proteins.
The impairment of this filtration process and/or the increased permeability of fibrinogen and β-lipoprotein into the arterial wall would result in the deposition of fibrin and/or lipid which evoke the proliferation of smooth muscle cells and might play an important role in the development of atherosclerosis.
The fibrin deposition tended to be detected earlier and more frequently than that of β-lipoprotein. This fact suggests that fibrin deposition might make a relatively major contribution in the development of preatheromatous lesion.