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Causative Factors for the Initiation of Atherosclerotic Plaques

Gary L Jones

Three main factors account for the accumulation of lipoprotein complexes at focal zones of the arterial tree which then can lead to plaque development: (a) diverging flow of the arterial tree which is punctuated at arterial bifurcations, (b) the arterial wall is a semi-permeable membrane with steady bulk flow of fluid, through the interstices of the intimal wall, and (c) shear dependent diffusivity of macromolecules which depends strongly on local shear rate. In the absence of the any factors, either no wall accumulation would occur or lipoproteins would form layers over the entire arterial tree. Models are developed and applied to various zones of an arterial branch, which shows large variations in wall accumulations. The models show that the most important aspects occur from the wall. Very high accumulations of lipids of factors of 2 to 6 times the bulk values in the recirculating flow downstream of branches or at aneurisms while other are show minimal accumulations.
These causative factors directly relate to clinical data, which links smoking to increased wall permeability and thus permeation rate, to incidence and severity of atherosclerotic plaques as well as substantial data linking high blood pressure affecting wall permeation rate with severity or incidence of plaque formation. There is also evidence of feedback whereby the local swelling of the intima increases the interstitial gaps which allow bulk fluid to pass more readily, thus accelerating the local accumulations in these zones.
This work integrates aspects, which have been studied separately but are not all present in previous work.