Adverse Effects of Environmental Stress: The Role of Harmful Algal Bloom Toxin Exposure in Cardiovascular Fibrosis Development in an Animal Model with Low and High Aerobic Capacity

• Grant number: 25/00305-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: April 01, 2025
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Tatiana de Sousa da Cunha Uchiyama
• Grantee: Lívia Bruni de Souza
• Supervisor: David J Kennedy
• Host Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Federal de São Paulo (UNIFESP). Campus São José dos Campos. São José dos Campos , SP, Brazil
• Institution abroad: University of Toledo (UT), United States
• Associated to the scholarship: 21/05331-1 - Role of probiotics Lactobacillus reuteri and Lactobacillus rhamnosus on the inflammatory profile and renin angiotensin system in an experimental model of chronic stress, BP.DR

Abstract

Stress is a prevalent aspect of modern life, influencing physiological and psychological processes. While mild stress may support adaptive responses, excessive or dysregulated stress is closely linked to adverse health outcomes, including cardiovascular disorders. Among environmental stressors, harmful algal blooms (HABs) have emerged as a critical area of research due to their possible detrimental effects on ecosystems, wildlife, and human health. HABs are often dominated by cyanobacteria species, with microcystins (MCs)-particularly the highly toxic MC-LR variant-being the most studied. The cardiovascular system is notably vulnerable to microcystin exposure, primarily due to mechanisms involving mitochondrial dysfunction, increased production of reactive oxygen species (ROS), oxidative stress, and alterations in paraoxonase (PON) activity. MCs have also been shown to induce cardiac fibrosis, a process mediated by the activation of f ibroblasts into myofibroblasts, largely driven by Angiotensin II. Angiotensin II plays a pivotal role in cardiovascular pathology, highlighting its clinical relevance. On the other hand, exercise emerges as a promising non-pharmacological intervention to counteract the deleterious effects of MCs, with regular aerobic activity well-documented to enhance cardiovascular health by reducing ROS production, improving antioxidant enzyme activity, and preserving mitochondrial function. This study hypothesizes that aerosol exposure to microcystins detrimentally impacts the cardiovascular system by inducing cardiac fibrosis through elevated proinflammatory cytokines, oxidative stress, and disruptions in the renin angiotensin system-characterized by increased Angiotensin II and decreased Angiotensin 1-7 levels. Furthermore, we hypothesize that rats with high exercise capacity will exhibit resilience to the cardiovascular effects of toxin exposure by preserving mitochondrial integrity, reducing oxidative stress, and promoting anti-inflammatory and antifibrotic pathways, ultimately protecting the cardiovascular system.