CRP3 participation in aortic aneurysm process

• Grant number: 15/11139-5
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2016
• End date: August 31, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Ayumi Aurea Miyakawa Yamaguchi
• Grantee: Ayumi Aurea Miyakawa Yamaguchi
• 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 researchers: José Eduardo Krieger

Abstract

The aortic aneurysm formation is characterized by inflammation with lymphocyte and macrophage infiltration, rupture of elastic and collagen fibers at media and adventitia layers, and loss of smooth muscle cells leading to the vascular wall narrowing. The inflammatory cells secrete cytokines and proteases that induce smooth muscle cell death and extracellular degradation. We have demonstrated that CRP3 (cysteine and glycine-rich protein-3) expression is controlled by mechanical stress where stretch increases its expression. During the aneurysm development, there is an increase of mechanical stress in the vascular wall due to the decrease of smooth muscle cells and extracellular matrix content. Our hypothesis is that CRP3 expression is increased in aneurysm and we will investigate the participation of CRP3 on smooth muscle cell rigidity, cytokine and protease secretion, and extracellular matrix production. The expression of CRP3 will be evaluated in human aneurysm samples and normal aorta segments. CRP3 expression will also be evaluated in animal model aneurysm and its development will be compared in wild type versus CRP3-knockout animals. The smooth muscle cells of wild type and CRP3-KO will be stimulated with inflammatory cytokine and mechanical stretch and extracellular production and degradation will be evaluated. CRP3 superexpression in cells deficient of CRP3 will be tested to attenuate aneurysm in animal model and the its potential as therapeutic target will be evaluated. (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)

GIRAO-SILVA, THAIS; FONSECA-ALANIZ, MIRIAM HELENA; DALLAN, LUIS ALBERTO OLIVEIRA; VALADAO, IURI CORDEIRO; DA ROCHA, HENRIQUE OLIVEIRA; KRIEGER, JOSE EDUARDO; MIYAKAWA, AYUMI AUREA. Human Saphenous Vein Endothelial Cell Isolation and Exposure to Controlled Levels of Shear Stress and Stretch. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, v. N/A, n. 194, p. 14-pg., 2023-04-01. (15/11139-5, 14/50889-7, 13/17368-0)

RIBEIRO-SILVA, JOAO CARLOS; NOLASCO, PATRICIA; KRIEGER, JOSE EDUARDO; MIYAKAWA, AYUMI AUREA. Dynamic Crosstalk between Vascular Smooth Muscle Cells and the Aged Extracellular Matrix. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 18, SEP 2021. (16/50439-7, 15/11139-5, 14/50889-7)

POLO, CARLA C.; FONSECA-ALANIZ, MIRIAM H.; CHEN, JIAN-HUA; EKMAN, AXEL; MCDERMOTT, GERRY; MENEAU, FLORIAN; KRIEGER, JOSE E.; MIYAKAWA, AYUMI A.. Three-dimensional imaging of mitochondrial cristae complexity using cryo-soft X-ray tomography. SCIENTIFIC REPORTS, v. 10, n. 1, DEC 3 2020. (14/25964-5, 15/11139-5, 13/17368-0)