Novel method for clarifying faster interstitial flow in the intimal side of the aorta under intraluminal pressurization

Abstract

Hypertension causes aortic thickening, especially on the intimal side. Although the production of the extracellular matrix is observed, the type of mechanical stress that produces this response remains unclear. In this study, we hypothesize that the interstitial flow causes the thickening. To validate this claim, we proposed a novel method to measure the velocity distribution in the radial direction in the aorta, which has been unclear. A fluorescent dye was introduced in the lumen of the mouse thoracic aorta ex vivo, intraluminal pressure was applied, and a time-lapse image in the radial-circumferential plane was acquired under a two-photon microscope. The flow of the fluorescent dye from the intimal to the adventitial sides in the aorta was successfully observed. The acquired image was converted to a radial-time image (i.e., kymograph), and the flow velocity was quantified by applying the one-dimensional advection-diffusion equation to the fluorescent images. The results revealed a higher interstitial flow velocity in the aortic walls under higher intraluminal pressure and a higher velocity on the more intimal side. Thus, the interstitial flow is a candidate for the mechanical stress causing hyperplasia of the aorta under hypertension.