Local Arterial Stiffening Assessed by MRI Precedes Atherosclerotic Plaque Formation

Abstract

Atherosclerosis is known to impair vascular function and cause vascular stiffening. The aim of this study was to evaluate the potential predictive role of vascular stiffening in the early detection of atherosclerosis. Therefore, we investigated the time course of early functional and morphological alterations of the vessel wall in a murine atherosclerosis model. Because initial lesions are distributed inhomogeneously in early-stage atherosclerosis, MR microscopy was performed to measure vascular elasticity locally, specifically the local pulse wave velocity and the arterial wall thickness. Local pulse wave velocity and the mean arterial wall thickness were determined in the ascending and the abdominal aortae of ApoE(-/-) and wild-type mice. In vivo MRI revealed that baseline pulse wave velocity and morphology were similar in 6-week-old ApoE(-/-) and WT mice, whereas at the age of 18 weeks, local pulse wave velocity was significantly elevated in ApoE(-/-) mice. Significantly increased vessel wall thickness was not found in ApoE(-/-) mice until the age of 30 weeks. Histological analysis of the aortae of ApoE(-/-) and WT mice showed that increased pulse wave velocity coincided with the fragmentation of the elastic laminae in the arterial wall, which is hypothesized to induce early vascular stiffening and may be promoted by macrophage-mediated matrix degradation. We newly report that the assessment of local pulse wave velocity via MRI provides early information about the local progression of atherosclerosis before macroscopic alterations of the vessel wall occur.