Study of gene expression in the vascular repair response after injury : effects of protein disulfide isomerase suppression

• Grant number: 10/06360-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2010
• End date: August 31, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Francisco Rafael Martins Laurindo
• Grantee: Haniel Alves Araujo
• 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 scholarship(s): 12/00014-9 - Integration between oxidative stress and inflammation mediated by myeloperoxidase in atherosclerosis vascular remodeling: role of protein disulfide isomerase and neutrophil nets, BE.EP.IC

Abstract

The vascular repair response after injury has broad significance as a prototype for common events responsible for physiological adaptations or pathological changes in vascular diseases. The processes that coordinate the vascular response, however, are unclear. In our group, we studied this response as a model of convergence between oxidative stress and stress of the endoplasmic reticulum (ER), both potentially dependent of protein disulfide isomerase (PDI), a chaperone of the ER associated to NADPH oxidase. This study is linked to the assumption that PDI may contribute to sustaining the response to vascular repair and growth of the neointima after vascular injury and that its inhibition, even partial, may represent an intervention capable of inhibiting vascular hyperplasia. The effects of vascular repair and PDI, studied in other projects of our laboratory, should also be followed by important changes in gene expression, whose knowledge will indicate changes in specific physiological programs. The main objective of this project is the development and application of a PCR array to study gene expression in rabbit iliac arteries after injury by angioplasty. The specific objectives are: 1) Identify genes involved in cell signaling pathways relevants to the mechanisms by which PDI modulates the vascular response to injury, involved in programs of physiological response to stress, redox balance, unfolded protein response, apoptosis and others. Specific primers will be designed and adapted to rabbit genome for analysis of gene expression of the arteries by PCR Array technique. 2) Investigate the time course of expression of PDI during the vascular response to injury. 3) Test and standardize the implementation of the PCR array. 4) Investigate, through the PCR array, the role of PDI in cellular processes associated with the response to injury. These results should amplify the understanding of the physiological implications of modulation of expression of PDI after vascular injury. (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)

TANAKA, LEONARDO Y.; ARAUJO, HANIEL A.; HIRONAKA, GUSTAVO K.; ARAUJO, THAIS L. S.; TAKIMURA, CELSO K.; RODRIGUEZ, ANDRES I.; CASAGRANDE, ANNELISE S.; GUTIERREZ, PAULO S.; LEMOS-NETO, PEDRO ALVES; LAURINDO, FRANCISCO R. M.. Peri/Epicellular Protein Disulfide Isomerase Sustains Vascular Lumen Caliber Through an Anticonstrictive Remodeling Effect. Hypertension, v. 67, n. 3, p. 613-622, MAR 2016. (09/54764-6, 10/06360-0, 13/07937-8)