Flow-Induced Vascular Remodeling in the Mouse

Abstract

Objective— Vascular remodeling of the carotid artery with intima-media thickness (IMT) is an important predictive factor for human cardiovascular disease. We characterized a mouse model of vascular remodeling. Methods and Results— The left external and internal carotid branches were ligated so that left carotid blood flow was reduced to flow via the occipital artery. In response to partial ligation of the left carotid artery (LCA), blood flow significantly decreased (−90%) in the LCA and increased (+70%) in the right carotid artery (RCA). Morphometry showed that both RCA and LCA underwent outward remodeling that was maximal at one week. Remodeling was greater in the RCA with predominantly increased lumen and very little increase in media or adventitia. In the LCA there was a dramatic increase in media with adventitia growth and intima formation. Correlation analysis indicated that the outward remodeling was more likely due to primary changes in the vessel wall rather than to changes in the lumen, such as shear stress. Mechanistic studies suggested roles for macrophage infiltration, upregulation of matrix metalloproteinase (MMP)-9, extracellular matrix reorganization, and vascular smooth muscle cell proliferation in LCA remodeling. Conclusions— The mouse model described here may be useful to define genetic determinants of IMT and identify new targets for therapy based on vascular remodeling.