Restoration of normal blood flow in atherosclerotic arteries promotes plaque stabilization

Morgan A. Schake; Ian S. McCue; Evan T. Curtis; Thomas J. Ripperda, Jr.; Samuel Harvey; Bryan T. Hackfort; Anna Fitzwater; Yiannis S. Chatzizisis; Forrest M. Kievit; Ryan M. Pedrigi

iScience (Jun 2023)

Restoration of normal blood flow in atherosclerotic arteries promotes plaque stabilization

Morgan A. Schake,
Ian S. McCue,
Evan T. Curtis,
Thomas J. Ripperda, Jr.,
Samuel Harvey,
Bryan T. Hackfort,
Anna Fitzwater,
Yiannis S. Chatzizisis,
Forrest M. Kievit,
Ryan M. Pedrigi

Affiliations

Morgan A. Schake: Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Ian S. McCue: Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Evan T. Curtis: Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
Thomas J. Ripperda, Jr.: Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Samuel Harvey: Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Bryan T. Hackfort: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
Anna Fitzwater: Institutional Animal Care Program, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
Yiannis S. Chatzizisis: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA; Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
Forrest M. Kievit: Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
Ryan M. Pedrigi: Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA; Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA; Nebraska Center for Integrated Biomolecular Communication, University of Nebraska-Lincoln, Lincoln, NE 68588, USA; Corresponding author

Journal volume & issue: Vol. 26, no. 6
p. 106760

Abstract

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Summary: 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 cuff was removed to allow restoration 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 decuffing was 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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