Annals of Biomedical Engineering

, Volume 42, Issue 6, pp 1185–1194

Pro-Atherogenic Shear Stress and HIV Proteins Synergistically Upregulate Cathepsin K in Endothelial Cells

  • Ivana Kennedy Parker
  • Ladeidra Monet Roberts
  • Laura Hansen
  • Rudolph L. GleasonJr.
  • Roy L. Sutliff
  • Manu O. Platt
Article

DOI: 10.1007/s10439-014-1005-9

Cite this article as:
Parker, I.K., Roberts, L.M., Hansen, L. et al. Ann Biomed Eng (2014) 42: 1185. doi:10.1007/s10439-014-1005-9

Abstract

Major advances in highly active antiretroviral therapies (HAART) have extended the lives of people living with HIV, but there still remains an increased risk of death by cardiovascular diseases (CVD). HIV proteins have been shown to contribute to cardiovascular dysfunction with effects on the different cell types that comprise the arterial wall. In particular, HIV-1 transactivating factor (Tat) has been shown to bind to endothelial cells inducing a range of responses that contribute to vascular dysfunction. It is well established that hemodynamics also play an important role in endothelial cell mediated atherosclerotic development. When exposed to low or oscillatory shear stress, such as that found at branches and bifurcations, endothelial cells contribute to proteolytic vascular remodeling by upregulating cathepsins, potent elastases and collagenases that contribute to altered biomechanics and plaque formation. Mechanisms to understand the influence of Tat on shear stress mediated vascular remodeling have not been fully elucidated. Using an in vivo HIV-Tg mouse model and an in vitro cone and plate shear stress bioreactor to actuate physiologically relevant pro-atherogenic or atheroprotective shear stress on human aortic endothelial cells, we have shown synergism between HIV proteins and pro-atherogenic shear stress to increase endothelial cell expression of the powerful protease cathepsin K, and may implicate this protease in accelerated CVD in people living with HIV.

Keywords

CathepsinHIVTatArterial remodelingShear stressEndothelial cells

Copyright information

© Biomedical Engineering Society 2014

Authors and Affiliations

  • Ivana Kennedy Parker
    • 1
    • 4
  • Ladeidra Monet Roberts
    • 2
  • Laura Hansen
    • 2
    • 4
  • Rudolph L. GleasonJr.
    • 1
    • 2
    • 4
  • Roy L. Sutliff
    • 3
  • Manu O. Platt
    • 2
    • 4
  1. 1.George W. Woodruff School of Mechanical EngineeringGeorgia Institute of TechnologyAtlantaUSA
  2. 2.Wallace H. Coulter Department of Biomedical EngineeringGeorgia Institute of TechnologyAtlantaUSA
  3. 3.Department MedicineEmory University/Atlanta VAMCAtlantaUSA
  4. 4.Petit Institute for Bioengineering and BioscienceGeorgia Institute of TechnologyAtlantaUSA