Effect of magnetic field stimulation on vascular structure and function: potential mechanisms of redox regulation

• Grant number: 23/05600-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): January 01, 2024
• Effective date (End): November 30, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Leonardo Yuji Tanaka
• Grantee: Ricardo Cesar Massucatto
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 18/07230-5 - Subcellular mechanisms underlying the convergence between redox and mechanic homeostasis on vascular regulation, AP.JP

Abstract

The electromagnetic force is one of the fundamental forces of nature, in this way, it participates in the reflections between tiny individuals and the large-scale behavior of all matter in the universe. Magnetic field (MF) effects have been reported to influence the biological behavior in several cell types during their evolutionary process, participating in homeostatic responses, pathological processes and exerting therapeutic effects, depending on the characteristic of the stimulus. Although the effects of MF exposure have been shown to play a role in a variety of biological contexts, the mechanisms underpinning most of the reported effects remain unclear. In the present study we sought to investigate the hypothesis that subcellular mechanisms of homeostatic regulation through redox processes connected with mechanoadaptation are important to determining vascular response to magnetic field exposure. Previous and our ongoing studies have demonstrated that the redox chaperone protein disulfide isomerase A1 (PDIA1) acts as an intermediate between these two processes, by coupling the local oxidant production to modulation of specific targets. Thus, the main aim of the present study is to investigate the effects of the static magnetic field on vascular structure and function and possible interaction with adaptive mechanisms through actin cytoskeleton under regulation of redox processes mediated by protein disulfide isomerase (PDIA1). Such changes may be the key to understanding the mechanical adaptation of cellular architecture to an external stimulus. For this understanding, ongoing and further studies will be carried out in aortic rings from healthy rats, under culture for 24 h being exposed or not to the static magnetic field (5 mT), in order to address effects on functional parameters such as vasomotricity and structural including viscoelastic properties. To elucidate potential mechanisms will be assessed more dynamic regulatory mechanic elements such as the cellular cytoskeleton and more chronic such as the collagen extracellular matrix. Yet, the potential targets of redox regulation will be focused on the pattern of cysteine oxidation through sulfenylation, as such modification has been involved in redox signaling during mechanoadaptation. In addition, the role of PDIA1 will be evaluated using pharmacologic inhibitors, further studies may involve a model of transgenic mouse overexpressing PDIA1. Thus, the present proposal may contribute to the body of knowledge of a fundamental force in the regulation vascular function and architecture as well to get insights over mechanistic knowledge of homeostatic responses through the interaction between redox processes and mechanobiology.