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Author Notes:

Corresponding Author information: Manu O. Platt, Ph.D., Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 315 Ferst Drive, Suite 1308, Atlanta, GA 30332, Email: manu.platt@bme.gatech.edu, Phone: +1 (404) 385-8531

Subjects:

Research Funding:

This work was completed with funding from NIH Award Number DP2OD007433 from the Office of the Director, National Institutes of Health (MOP).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Cardiovascular
  • Cathepsins
  • Endothelial cells
  • Sickle cell
  • HIV
  • Shear stress
  • WALL SHEAR-STRESS
  • LYSOSOMAL CYSTEINE PROTEASES
  • ABDOMINAL AORTIC-ANEURYSM
  • IMMUNODEFICIENCY-VIRUS TYPE-1
  • CYSTATIN-C DEFICIENCY
  • HIV-INFECTED PATIENTS
  • MONOCYTE ADHESION
  • MATRIX-METALLOPROTEINASE
  • REDUCES ATHEROSCLEROSIS
  • CAROTID ATHEROSCLEROSIS

Endothelial cells and cathepsins: Biochemical and biomechanical regulation

Tools:

Journal Title:

Biochimie

Volume:

Volume 122

Publisher:

, Pages 314-323

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Cathepsins are mechanosensitive proteases that are regulated not only by biochemical factors, but are also responsive to biomechanical forces in the cardiovascular system that regulate their expression and activity to participate in cardiovascular tissue remodeling. Their elastinolytic and collagenolytic activity have been implicated in atherosclerosis, abdominal aortic aneurysms, and in heart valve disease, all of which are lined by endothelial cells that are the mechanosensitive monolayer of cells that sense and respond to fluid shear stress as the blood flows across the surfaces of the arteries and valve leaflets. Inflammatory cytokine signaling is integrated with biomechanical signaling pathways by the endothelial cells to transcribe, translate, and activate either the cysteine cathepsins to remodel the tissue or to express their inhibitors to maintain healthy cardiovascular tissue structure. Other cardiovascular diseases should now be included in the study of the cysteine cathepsin activation because of the additional biochemical cues they provide that merges with the already existing hemodynamics driving cardiovascular disease. Sickle cell disease causes a chronic inflammation including elevated TNFα and increased numbers of circulating monocytes that alter the biochemical stimulation while the more viscous red blood cells due to the sickling of hemoglobin alters the hemodynamics and is associated with accelerated elastin remodeling causing pediatric strokes. HIV-mediated cardiovascular disease also occurs earlier in than the broader population and the influence of HIV-proteins and antiretrovirals on endothelial cells must be considered to understand these accelerated mechanisms in order to identify new therapeutic targets for prevention.

Copyright information:

© 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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