Restoration of normal blood flow in atherosclerotic arteries promotes plaque stabilization

Authors

Morgan A. Schake, University of Nebraska- Lincoln
Ian McCue, University of Nebraska- LincolnFollow
Evan T. Curtis, University of Nebraska- LincolnFollow
Thomas J. Ripperda Jr., University of Nebraska- Lincoln
Samuel Harvey, University of Nebraska- Lincoln
Bryan T. Hackfort, University of Nebraska Medical CenterFollow
Anna Fitzwater, University of Nebraska- LincolnFollow
Yiannis S. Chatzizisis, University of Nebraska Medical Center
Forrest Kievit, University of Nebraska- LincolnFollow
Ryan M. Pedrigi, University of Nebraska - Lincoln, University of Nebraska Medical CenterFollow

Date of this Version

6-16-2023

Citation

Schake et al., iScience 26, 106760 June 16, 2023. https://doi.org/10.1016/ j.isci.2023.106760

Comments

Open access.

Abstract

Blood flow is a key regulator of atherosclerosis. Disturbed blood flow promotes atherosclerotic plaque development, whereas normal blood flow protects against plaque development. We hypothesized that normal blood flow is also therapeutic, if it were able to be restored within atherosclerotic arteries. Apolipoprotein E-deficient (ApoE^-/-) mice were initially instrumented with a blood flow-modifying cuff to induce plaque development and then five weeks later the cuffwas removed to allowrestoration of normal blood flow. Plaques in decuffed mice exhibited compositional changes that indicated increased stability compared to plaques in mice with the cuff maintained. The therapeutic benefit of decuffingwas comparable to atorvastatin and the combination had an additive effect. In addition, decuffing allowed restoration of lumen area, blood velocity, and wall shear stress to near baseline values, indicating restoration of normal blood flow. Our findings demonstrate that the mechanical effects of normal blood flow on atherosclerotic plaques promote stabilization.