Circulating Total Extracellular Vesicles Cargo Are Associated with Age-Related Oxidative Stress and Susceptibility to Cardiovascular Diseases: Exploratory Results from Microarray Data
Laura Reck Cechinel,
Rachael Ann Batabyal,
Giana Blume Corssac,
Madeleine Goldberg,
Brennan Harmon,
Virgínia Mendes Russo Vallejos,
Gisele E. Bruch,
André Ricardo Massensini,
Adriane Belló-Klein,
Alex Sander da Rosa Araujo,
Robert J. Freishtat,
Ionara Rodrigues Siqueira
Affiliations
Laura Reck Cechinel
Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, RS, Brazil
Rachael Ann Batabyal
Center for Genetic Medicine Research, Children’s National Research Institute, Washington, DC 20012, USA
Giana Blume Corssac
Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, RS, Brazil
Madeleine Goldberg
Center for Genetic Medicine Research, Children’s National Research Institute, Washington, DC 20012, USA
Brennan Harmon
Center for Genetic Medicine Research, Children’s National Research Institute, Washington, DC 20012, USA
Virgínia Mendes Russo Vallejos
Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil
Gisele E. Bruch
Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil
André Ricardo Massensini
Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil
Adriane Belló-Klein
Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, RS, Brazil
Alex Sander da Rosa Araujo
Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, RS, Brazil
Robert J. Freishtat
Center for Genetic Medicine Research, Children’s National Research Institute, Washington, DC 20012, USA
Ionara Rodrigues Siqueira
Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, RS, Brazil
Aging is a risk factor for many non-communicable diseases such as cardiovascular and neurodegenerative diseases. Extracellular vesicles and particles (EVP) carry microRNAs that may play a role in age-related diseases and may induce oxidative stress. We hypothesized that aging could impact EVP miRNA and impair redox homeostasis, contributing to chronic age-related diseases. Our aims were to investigate the microRNA profiles of circulating total EVPs from aged and young adult animals and to evaluate the pro- and antioxidant machinery in circulating total EVPs. Plasma from 3- and 21-month-old male Wistar rats were collected, and total EVPs were isolated. MicroRNA isolation and microarray expression analysis were performed on EVPs to determine the predicted regulation of targeted mRNAs. Thirty-one mature microRNAs in circulating EVPs were impacted by age and were predicted to target molecules in canonical pathways directly related to cardiovascular diseases and oxidative status. Circulating total EVPs from aged rats had significantly higher NADPH oxidase levels and myeloperoxidase activity, whereas catalase activity was significantly reduced in EVPs from aged animals. Our data shows that circulating total EVP cargo—specifically microRNAs and oxidative enzymes—are involved in redox imbalance in the aging process and can potentially drive cardiovascular aging and, consequently, cardiac disease.
