Mostly Biomathematics Lunchtime Seminar

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What modeling and aquaporin-1 can teach us about early atherosclerosis

Speaker: David Rumschitzki, The City College of New York

Location: Warren Weaver Hall 1314

Date: Tuesday, February 27, 2018, 12:30 p.m.

Synopsis:

Atherosclerosis or hardening of the arteries is the leading cause of death in the US and in all Western countries. It begins with the transport of the molecular aggregate, low density lipoprotein (LDL) cholesterol, from the blood across the endothelial cell monolayer that lines the vessel wall and into the artery wall, where it can bind to extracellular matrix in the intima wall layer and accumulate there. Such accumulation sets off a chain of events that can lead to early lesions and eventually to atherosclerosis.

In this talk we shall discuss several models that we have built and the corresponding experiments that we have carried out that clarify the detailed mechanism of a number of these earliest events. These include fluid mechanics and mass transfer models to explain the entry into and spread of LDL in the vessel wall, models that naturally link to kinetic models for its accumulation there. A smaller scale model explains the surprising dependence of the vessel wall hydraulic conductivity on the transmural pressure in terms of its effect on artery wall mechanics.  We then show experimental evidence that the membrane protein aquaporin-1 plays an important role in artery wall transport and develop theory that drives experimental work and resolves an oncotic paradox. The results suggest a possible path to a new approach to preventing or slowing down atherosclerotic lesion formation.