Effect of circulating microparticles from post-COVID-19 patients on endothelial function: protein restriction impact

• Grant number: 23/01329-8
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2023
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Agreement: CNPq
• Principal Investigator: Ana Paula Couto Davel
• Grantee: Ana Paula Couto Davel
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 20/09799-5 - Microparticles and endothelial function in patients with COVID-19: effects of bradykinin blockade, AP.R
• Associated scholarship(s): 23/10663-9 - Effect of circulating microparticles from post-COVID-19 patients on endothelial function: protein restriction impact, BP.JD

Abstract

The SARS-CoV-2 infection, known as COVID-19, has caused millions of deaths worldwide. In the survivors of this disease, cardiovascular symptoms can be observed until 12 months after the diagnosis, in the post-COVID phase. It has been suggested that microparticles (MP) could contribute to worsening the COVID-19 in the long term. These extracellular vesicles have the ability to carry bioactive molecules and thus interfere with the cellular and tissue signaling pathways. Beyond the direct impact on people's health, the COVID-19 pandemic also affected the economy, which disturbed the food distribution, increasing people suffering from malnutrition in low- and middle-income countries. Malnutrition deteriorates organs and systems and is associated with higher risk of infections and cardiovascular diseases. As MP can mediate vascular injury, in the present project we hypothesized that isolated MP from patients after hospital discharge from severe COVID-19 may contribute to endothelial damage signaling, especially in the coexistence with malnutrition. For that, MP were isolated from collected blood samples of patients with COVID-19, 1, 4 and 24 weeks after hospital discharge (clinical trial ITHACA-PMID 33472675). The endothelial consequences following MP incubation (105 e 106/mL) will be evaluated comparing standard and protein restriction in vitro and in situ. For that, endothelial cells will be cultivated in vitro with standard media (100% amino acids) and protein restriction media (25% amino acids) then incubated with MP or vehicle to evaluate gene and protein expression of pro-inflammatory factors, leukocytes adhesion molecules, components of renin-angiotensin system, production of reactive oxygen species, nitric oxide and prostanoids. To investigate MP impact on the endothelial-dependent vasodilation function, isolated aorta from male mice fed through 3 months with standard or protein restriction (6% protein) diet will be incubated with MP or vehicle in situ. After incubation, acetylcholine-induced endothelium-dependent vasodilation response will be evaluated in the presence and absence of inhibition of vasoactive agents released from endothelial cells. At last, isolated MP from the post-COVID-19 phase will be analyzed through comparative proteomic. That methodological approach intends to enlarge the knowledge about molecular mechanisms associated with endothelial injury in the post-COVID-19 phase, particularly in increased risk conditions to cardiovascular damage as malnutrition. (AU)