A Multiscale Model of Atherosclerotic Plaque Formation at Its Early Stage

Abstract

A multiscale model of atherosclerotic plaque formation at its early stage has been developed in order to integrate the various phenomena leading to fatty streak formation. The different scales considered in this model are in both the spatial domain (from cellular to organism level) and the time domain (from seconds to months). The cellular level was considered by modeling the transport and chemical interactions of low-density lipoproteins (LDL) and other agents in a stenosed artery. This was linked to arterial thickening (organ level). Mean blood LDL level (organism level) was selected as one of the critical factors for atherosclerotic formation along with wall shear stress (WSS) exerted on the endothelium (the inner portion of the artery). It was observed that plaque location was dependent on WSS and that plaque size, number, and growth was dependent on mean blood LDL levels as well.

Mathematical modelling of atheroma plaque formation and development in coronary arteries

“…Furthermore, there are three transport pathways through the endothelium: vesicular transcytosis, which is regulated by receptors on the endothelial cells [20], and through leaky and normal junctions, most of which are located at the sites of dying or replicating cells [21]. Apart from the LDL molecules, many studies have focused on the governing mechanics interaction of the different biological species which play a role in atheroma plaque development from both experimental (see [22 -24], among others) and computational (see [25][26][27][28], among others) points of view. Furthermore, there are greatly varying degrees of complexity in these computational studies depending on the number of species considered and the development of the equations proposed.…”

“…Cobbold et al [30] and Gessaghi et al [31] studied the oxidation process of LDL cholesterol within the context of an in vitro framework. In addition, Cobbold et al [30] considered the action of different vitamins such as vitamin E or C. Di Tomaso et al [26] considered the interaction between just two species, LDL and monocytes, but monocyte behaviour was modelled in a very simple way. Fok [32] proposed a mathematical model of intimal thickening, posed as a free boundary problem.…”

Stages of atherosclerotic plaque development and unstable plaque types: pathophysiologic and histologic characteristics

“…Последующая трансформация макрофагов в ХС-нагру-женные пенистые клетки (ПК) приводит к постепен-ному нарастанию сначала внутриклеточного, а затем и внеклеточного накопления липидов в субэндотели-альном пространстве, что является морфологической основой липидного пятна/полоски [13][14][15].…”

“…Активированные МФ играют важную роль в разви-тии воспаления в фиброзной бляшке и формировании нестабильной бляшки, так как они: а) секретируют зна-чительное количество воспалительных цитокинов, запускающих каскад воспалительных изменений в очаге, б) сами активно продуцируют и стимулируют продукцию эндотелиоцитами тканевого фактора, уси-ливающего проникновение в субэндотелиальное про-странство и в бляшку моноцитов, Т-ЛФ, нейтрофилов и других клеток, в) продуцируют большое количество активных кислородных метаболитов, активирующих в бляшке окислительные изменения, особенно про-цессы окисления липидов, ХС, посредством цитокинов и хемокинов, а также за счет повышения процессов апоптоза в ядре бляшки, способствуют снижению рези-стентности фиброзной покрышки бляшки [14,16].…”

Multiscale Modeling in Vascular Disease and Tissue Engineering

“…A multiscale model of early stage atherosclerotic plaque formation has recently been developed in order to integrate the various mechano-biological phenomena leading to fatty streak formation [19]. The different scales considered in this model are in both the spatial domain (from cellular to organism level) and the time domain (from seconds to months).…”