Emerging roles of thiol oxidoreductase-dependent mechanisms on vasomotricity regulation

Author(s)

Portas, Carolina Morales ; Garcia, Geovana Stefani ; Gaspar, Renato Simoes ; Casagrande, Annelise da Silva ; Tanaka, Leonardo Yuji

• Document type: Journal article
• Source: ADVANCES IN REDOX RESEARCH; v. 6, p. 11-pg., 2022-12-01.

Abstract

Vasomotricity, defined by measurements of contraction or relaxation, is important to support correct blood supply and needs to be finely regulated during hemodynamic changes. Disruptions in either contraction or relaxation, mainly endothelium-mediated, are closely related to cardiovascular diseases and are found during early events of vascular structural alterations, including vessel remodeling. Both acute vasomotor changes and chronic vascular remodeling are regulated by redox processes, such as the production of nitric oxide (NO), which is the major vasoactive endothelium-derived paracrine molecule. However, it is still unclear if vasomotricity can be regulated by direct redox reactions or thiol posttranslational modifications induced by secondary mediators. Here, we have reviewed the literature concerning the control of vascular function based on redox processes and merged evidence with mechanisms supporting structural alterations. Such knowledge is important to summarize the resulting vascular effects that occur upon inhibition of specific redox regulators. This may provide a landscape to better understand the complex redox regulation of vasomotricity and determine a hierarchical map of events involving NO biology, calcium transient regulation, actin cytoskeleton and extracellular matrix organization. In addition, we have proposed that the thiol oxidoreductase protein disulfide isomerase A1 (PDI) has the potential to act as a central hub connecting these processes with local oxidant generation, which may globally impact vascular function in physiologic and pathologic processes. Altogether, the understanding of these redox processes may lead to potential therapeutic redox targets able to prevent or treat functional or structural vascular alterations. (AU)

• FAPESP's process: 20/04280-1 - Subcellular mechanisms underlying the convergence between redox and mechanic homeostasis on vascular regulation
• Grantee: Leonardo Yuji Tanaka
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 20/15944-8 - Investigation of peri/epicellular protein disulphide isomerase as a novel regulator of the platelet-endothelium interaction in normoglycaemia and Diabetes
• Grantee: Renato Simões Gaspar
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/07230-5 - Subcellular mechanisms underlying the convergence between redox and mechanic homeostasis on vascular regulation
• Grantee: Leonardo Yuji Tanaka
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 19/18448-4 - Study of nitric oxide-dependent modulation of physiologic and pathologic cyclic stretch set point in endothelial cells
• Grantee: Geovana Stefani Garcia
• Support Opportunities: Scholarships in Brazil - Scientific Initiation