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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Vascular remodeling: A redox-modulated mechanism of vessel caliber regulation

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Author(s):
Tanaka, Leonardo Y. ; Laurindo, Francisco R. M.
Total Authors: 2
Document type: Review article
Source: Free Radical Biology and Medicine; v. 109, n. SI, p. 11-21, AUG 2017.
Web of Science Citations: 14
Abstract

Vascular remodeling, i.e. whole-vessel structural reshaping, determines lumen caliber in (patho) physiology. Here we review mechanisms underlying vessel remodeling, with emphasis in redox regulation. First, we discuss confusing terminology and focus on strictu sensu remodeling. Second, we propose a mechanobiological remodeling paradigm based on the concept of tensional homeostasis as a setpoint regulator. We first focus on shear-mediated models as prototypes of remodeling closely dominated by highly redox-sensitive endothelial function. More detailed discussions focus on mechanosensors, integrins, extracellular matrix, cytoskeleton and inflammatory pathways as potential of mechanisms potentially coupling tensional homeostasis to redox regulation. Further discussion of remodeling associated with atherosclerosis and injury repair highlights important aspects of redox vascular responses. While neointima formation has not shown consistent responsiveness to antioxidants, vessel remodeling has been more clearly responsive, indicating that despite the multilevel redox signaling pathways, there is a coordinated response of the whole vessel. Among mechanisms that may orchestrate redox pathways, we discuss roles of superoxide dismutase activity and extracellular protein disulfide isomerase. We then discuss redox modulation of aneurysms, a special case of expansive remodeling. We propose that the redox modulation of vascular remodeling may reflect (1) remodeling pathophysiology is dominated by a particularly redox-sensitive cell type, e.g., endothelial cells (2) redox pathways are temporospatially coordinated at an organ level across distinct cellular and acellular structures or (3) the tensional homeostasis setpoint is closely connected to redox signaling. The mechanobiological/redox model discussed here can be a basis for improved understanding of remodeling and helps clarifying mechanisms underlying prevalent hard-to-treat diseases. (AU)

FAPESP's process: 13/17115-5 - Epi/pericellular protein disulfide isomerase: a novel regulator of biomechanical adaptation in vascular cells
Grantee:Leonardo Yuji Tanaka
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 09/54764-6 - Regulation of redox homeostasis and integrated stress response by Protein Disulfide Isomerase (PDI): mechanisms and role in the pathophysiology and therapy of vascular diseases
Grantee:Francisco Rafael Martins Laurindo
Support type: Research Projects - Thematic Grants