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
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.
