Atherosclerosis increases adventitial pressure and limits solute transport via fluid-balance mechanisms.

The adventitia of blood vessels is their structural interface with surrounding tissues and may also contribute importantly to atherogenesis. Adventitial vasa vasorum and lymphatic vessels provide sources and sinks of interstitial fluid and solutes and remodel in disease. We constructed a mathematical model to investigate how soluble disease mediators, including lipoproteins and cytokines, are transported through the artery wall in healthy and atherosclerotic conditions. We derived model parameters from in vivo measurements where possible and extensively investigated the sensitivity of fluid flow and solute transport to them. Adventitial interstitial fluid pressure is predicted to increase in atherosclerosis because of a shift in transmural fluxes across vasa vasorum and lymphatics. In healthy conditions, 40-80% of the fluid gathered by lymphatics originates from vasa vasorum, and this increases to 60-90% in atherosclerosis. The increased dilution of fluid flowing from the inner layers in atherosclerosis implies that solute transport from the media to the adventitia is impaired. This implies increased concentration gradients near the external elastic lamina that may increase immune-cell retention there, and decreased gradients in the outer adventitia that may reduce immune-cell attraction from there.