Modulation of vascular injury response by protein disulfide isomerase-A1

• Grant number: 21/14131-6
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2022
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Francisco Rafael Martins Laurindo
• Grantee: Júlia Martins Felipe de Souza
• 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: 13/07937-8 - Redoxome - Redox Processes in Biomedicine, AP.CEPID

Abstract

The vascular response to mechanical injury is a phenomena model that occurs in various vascular diseases. Certain mechanisms, such as redox signaling, may permeate the natural story of injury response and affect the variables of the final response. Data from our group lead to the general hypothesis that Protein-Disulfide Isomerase (PDIA1), a redox chaperone from the endoplasmic reticulum and cell surface, is a primary factor in the mechanobiological regulation of the cell-matrix binomial architecture in vessels and thus has a significant pathophysiological role, including a potential therapeutic target, in vascular remodeling. In this project, we intend to analyze several aspects of vascular response in transgenic mice that overexpress PDIA1. The specific objectives are: 1) characterizing a model of arterial response to mechanical injury in mice, analyzing morphological variables and molecular markers of proliferation, differentiation, mesenchymal transition, ER stress, senescence and cell death at different times after injury; 2) analyzing the effect of constitutive transgenic superexpression of PDIA1 (TgDia1) on morphostructural variables and molecular markers validated in objective 1; 3) investigating cell signaling mechanisms involved in the effects of PDIA1, with emphasis on redox processes; 4) evaluating biomechanics and vascular function in wild-type and TgPDIA1 mice. The results of this study may evidence relevant mechanisms of the effect of PDIA1 on the biopathology of vascular cells and synergize with other studies of our group evidencing a new code of redox signaling by protein disulfide isomerases. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PORTO, FERNANDO GARCEZ; TANAKA, LEONARDO YUJI; DE BESSA, TIPHANY CORALIE; OLIVEIRA, PERCILLIA VICTORIA SANTOS; DE SOUZA, JULIA MARTINS FELIPE; KAJIHARA, DANIELA; FERNANDES, CAROLINA GONCALVES; SANTOS, PATRICIA NOLASCO; LAURINDO, FRANCISCO RAFAEL MARTINS. Evidence for a protective role of Protein Disulfide Isomerase-A1 against aortic dissection. ATHEROSCLEROSIS, v. 382, p. 9-pg., 2023-09-27. (21/14131-6, 13/07937-8, 18/07230-5, 14/24511-7, 19/03617-5, 18/07511-4, 17/11410-6)