Subcellular mechanisms underlying the convergence between redox and mechanic homeostasis on vascular regulation

• Grant number: 18/07230-5
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: December 01, 2018
• End date: November 30, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Leonardo Yuji Tanaka
• Grantee: Leonardo Yuji Tanaka
• 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): 23/05600-8 - Effect of magnetic field stimulation on vascular structure and function: potential mechanisms of redox regulation, BP.IC; 22/16629-4 - Subcellular mechanisms underlying the convergence between redox and mechanic homeostasis on vascular regulation, BP.JP; 20/04280-1 - Subcellular mechanisms underlying the convergence between redox and mechanic homeostasis on vascular regulation, BP.JP; + associated scholarships 19/18448-4 - Study of nitric oxide-dependent modulation of physiologic and pathologic cyclic stretch set point in endothelial cells, BP.IC; 19/18450-9 - Effect of angiotensin II in redox-dependent mechanoresponse in vascular smooth muscle cells, BP.IC; 19/09829-4 - Study of subcellular mechanisms of redox and tension-associated processes in vascular smooth muscle cells (VSMC) in a model of pro-atherogenic blood flow, BP.MS - associated scholarships

Abstract

The study concerning on how cells adapt to distinct mechanical forces, translating physical stimulus in to chemical signals, is such a remarkable issue from mechanobiology, with direct implications on pathophysiology, particularly cardiovascular diseases. Growing evidences point out that redox pathways of cell signaling are fundamental mediators of mechanoadaptive responses. However, the mechanisms by which such physical stimuli promote controlled oxidant species generation and the local impact of these intermediates over effectors of cell mechanics control are still poorly known. The present project approaches such mechanisms through the hypothesis that the return to the tensional homeostasis after a mechanic challenge is mediated by fine tune regulation of redox processes. The main goal is to investigate the mechanisms regulating the convergence between redox and tensional homeostasis over the vascular structure and function - and specifics are: 1) to investigate in Vascular Smooth Muscle Cells (VSMC) how mechanic stimulation affects redox processes regulation which influences the mechanoresponse; 2) to analyze how the redox status modulation and oxidant species generation regulate the mechanic response in VSMC; and 3) to study in animal model the effects of physiologic and pathologic mechano stimulation in mechanisms regulating redox processes over mechanic adaptation in conductance vessel. The approaches include distinct mechanostressors in cells and tissues, coupled to real time analysis concerning molecular force sensors and modulation of subcellular oxidants and redox status. Overall, through these experiments will be possible to analyze compartmentalized redox events associated to cell and tissue mechanoadaptive responses. Such knowledge will contribute to get improves on mechanobiological/redox paradigm involving the homeostatic control and cardiovascular diseases development including vascular remodeling. (AU)

Scientific publications

(6)

(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.; KUMAR, SANDEEP; GUTIERRE, LUCAS F.; MAGNUN, CELSO; KAJIHARA, DANIELA; KANG, DONG-WON; LAURINDO, FRANCISCO R. M.; JO, HANJOONG. Disturbed flow regulates protein disulfide isomerase A1 expression via microRNA-204. FRONTIERS IN PHYSIOLOGY, v. 15, p. 14-pg., 2024-04-04. (20/04280-1, 13/07937-8, 15/15281-0, 18/07230-5)

NOLASCO, PATRICIA; FERNANDES, CAROLINA GONCALVES; RIBEIRO-SILVA, JOAO CARLOS; OLIVEIRA, PERCILLIA V. S.; SACRINI, MARIANA; DE BRITO, ISIS VASCONCELOS; DE BESSA, TIPHANY CORALIE; PEREIRA, LYGIA V.; TANAKA, LEONARDO Y.; ALENCAR, ADRIANO; et al. Impaired vascular smooth muscle cell force-generating capacity and phenotypic deregulation in Marfan Syndrome mice. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v. 1866, n. 1, JAN 1 2020. (18/07230-5, 14/24511-7, 13/07937-8, 14/20595-1)

TANAKA, LEONARDO Y.; OLIVEIRA, PERCILLIA V. S.; LAURINDO, FRANCISCO R. M.. Peri/Epicellular Thiol Oxidoreductases as Mediators of Extracellular Redox Signaling. Antioxidants & Redox Signaling, v. 33, n. 4, FEB 2020. (18/07230-5, 13/07937-8, 19/03617-5)

FERNANDES, DENISE C.; WOSNIAK JR, JOAO; GONCALVES, RENATA C.; TANAKA, LEONARDO Y.; FERNANDES, CAROLINA G.; ZANATTA, DANIELA B.; DE MATTOS, ANA BARBOSA M.; STRAUSS, BRYAN E.; LAURINDO, FRANCISCO R. M.. PDIA1 acts as master organizer of NOX1/NOX4 balance and phenotype response in vascular smooth muscle. Free Radical Biology and Medicine, v. 162, p. 603-614, JAN 2021. (13/07937-8, 18/07230-5, 09/54764-6, 13/03363-7)

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)

PORTAS, CAROLINA MORALES; GARCIA, GEOVANA STEFANI; GASPAR, RENATO SIMOES; CASAGRANDE, ANNELISE DA SILVA; TANAKA, LEONARDO YUJI. Emerging roles of thiol oxidoreductase-dependent mechanisms on vasomotricity regulation. ADVANCES IN REDOX RESEARCH, v. 6, p. 11-pg., 2022-12-01. (20/04280-1, 20/15944-8, 18/07230-5, 19/18448-4)