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Variation in Cardiac Pulse Frequencies Modulates vSMC Phenotype Switching During Vascular Remodeling

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Abstract

In vitro perfusion systems have exposed vascular constructs to mechanical conditions that emulate physiological pulse pressure and found significant improvements in graft development. However, current models maintain constant, or set pulse/shear mechanics that do not account for the natural temporal variation in frequency. With an aim to develop clinically relevant small diameter vascular grafts, these investigations detail a perfusion culture model that incorporates temporal pulse pressure variation. Our objective was to test the hypothesis that short-term variation in heart rate, such as changes in respiratory activity, plays a significant role in vascular remodeling and graft development. The pulse rate of a healthy volunteer was logged to model the effect of daily activities on heart rate. Vascular bioreactors were used to deliver perfusion conditions based on modeled frequencies of temporal pulse variability, termed Physiologically Modeled Pulse Dynamics (PMPD). Acellular scaffolds derived from the human umbilical vein were seeded with human vascular smooth muscle cells and perfused under defined pulsatile conditions. vSMC exposed to constant pulse frequencies expressed a contractile phenotype, while exposure to PMPD drove cells to a synthetic state with continued cell proliferation, increased tensile strength and stiffness as well as diminished vasoactivity. Results show the temporal variation associated with normal heart physiology to have a profound effect on vascular remodeling and vasoactive function. While these models are representative of vascular regeneration further investigation is required to understanding these and other key regulators in vSMC phenotype switching in non-pathological or wound healing states. This understanding has important clinical implications that may lead to improved treatments that enhance vessel regeneration.

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Acknowledgments

This work was supported by the National Institutes of Health (Grants R01-HL088207 and R01-HL088207-03S1).

Conflict of Interest

Peter S. McFetridge and Zehra Tosun declare that they have no conflict of interest.

Statement of Human Studies

No human studies were carried out by the authors for this article.

Statement of Animal Studies

No animal studies were carried out by the authors for this article.

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Authors and Affiliations

  1. J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Drive, Biomedical Sciences Building, JG-56, Gainesville, FL, 32611, USA

    Zehra Tosun & Peter S. McFetridge

Authors
  1. Zehra Tosun
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  2. Peter S. McFetridge
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Correspondence to Peter S. McFetridge.

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Associate Editor Ajit P. Yoganathan oversaw the review of this article.

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Tosun, Z., McFetridge, P.S. Variation in Cardiac Pulse Frequencies Modulates vSMC Phenotype Switching During Vascular Remodeling. Cardiovasc Eng Tech 6, 59–70 (2015). https://doi.org/10.1007/s13239-014-0204-8

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  • DOI: https://doi.org/10.1007/s13239-014-0204-8

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