Establishment of the in vitro cardiovascular model derived from human Pluripotent Stem Cells (hiPSCs) for functional analysis of Hypertension

• Grant number: 20/03108-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2021
• End date: January 26, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Lygia da Veiga Pereira
• Grantee: Raquel Delgado Sarafian
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/08135-2 - CTC - Center for Cell-Based Therapy, AP.CEPID
• Associated scholarship(s): 23/00966-4 - Characterizing NADPH oxidase-dependent ROS production and redox signalling in hiPSC-derived cardiovascular cells from normotensive and hypertensive subjects, BE.EP.DR

Abstract

Hypertension is an important risk factor for several cardiovascular diseases, such as stroke, acute myocardial infarction, and chronic kidney disease. It is a complex, multifactorial disease, using cellular/molecular mechanisms that are not well understood. Increasing evidence in recent decades may cause an association between Reactive Oxygen Species (ROS, English, Reactive Oxygen Species) and arterial Hypertension. As ROS are essential for cell physiology, but in an unbalanced situation of exacerbated ROS production, they can damage cellular components and trigger pathological processes. In this scenario, many animal models, primary cells, tumoral or immortalized lineages are common as study models, but these are limited by not being reliably reflected or if they are found in humans or by not using easily accessible primary animals, such as this is the case with cardiac cells. The use of human-induced pluripotent stem cells (hiPSC) allows the generation of primary cells relevant to the disease, thus being a powerful tool for understanding mechanisms of the cellular mechanism in response to oxidative stress in the dysfunction of cardiovascular cells caused by Hypertension. In the present work, we propose to generate a model of cardiovascular study in vitro that is capable of recapitulating or hypertensive phenomenon from a collection of hiPSCs derived from hypertensive and normotensive individuals. Investigate in particular differences between groups related to oxidative metabolism. (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)

CARVALHO, LAURA MACHADO LARA; BRANCO, ELISA VARELLA; SARAFIAN, RAQUEL DELGADO; KOBAYASHI, GERSON SHIGERU; DE ARAUJO, FABIANO TOFOLI; SOUZA, LUCAS SANTOS; MOREIRA, DANIELLE DE PAULA; HSIA, GABRIELLA SHIH PING; BERTOLLO, ENY MARIA GOLONI; BUCK, CECILIA BARBOSA; et al. Establishment of iPSC lines and zebrafish with loss-of-function AHDC1 variants: Models for Xia-Gibbs syndrome. Gene, v. 871, p. 10-pg., 2023-04-22. (20/03108-0, 20/04744-8, 13/08028-1, 20/10168-0, 18/08486-3, 19/02605-3)