Perivascular adipose tissue in Renovascular Hypertension: mineralocorticoid receptor as a therapeutic target

• Grant number: 21/04234-2
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): October 01, 2021
• Effective date (End): September 30, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Luciana Venturini Rossoni
• Grantee: Daniela Esteves Ferreira dos Reis Costa
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Renovascular Hypertension is the main cause of secondary and treatment-resistant Hypertension, which correlates with an obstruction of the renal arteries and progressive reduction of renal perfusion, leading to chronic and sustained activation of the renin-angiotensin-aldosterone system. Aldosterone is considered an important therapeutic target in Hypertension and its effects are mediated by the activation of the Mineralocorticoid Receptor (MR). Initially thought to be expressed only in the kidney, the MR receptor is now known to have an extensive extra-renal distribution, including in the heart, vasculature and, more recently, in the adipose tissue, as in the Perivascular Adipose Tissue (PVAT). PVAT is strongly associated with the cardiovascular system for secreting several vasoactive substances that influence vascular homeostasis. Under physiological conditions, PVAT is known for its anticontractile effect for secreting vasodilator substances. However, in cardiometabolic diseases, such as Hypertension, studies have demonstrated the loss of its anticontractile effect, suggesting that PVAT plays a significant role in the pathogenesis of Hypertension. However, the mechanisms responsible for impairing the anticontractile effect of PVAT in Hypertension are still unknown and, until now, there are no studies in the literature addressing the role of MR receptor activation, specifically in the PVAT, contributing to vascular dysfunction in Renovascular Hypertension. Thus, this project aims to investigate whether hyperactivation of the MR receptor in perivascular adipocytes participates in the PVAT dysfunction, leading to the release of reactive oxygen species and inflammatory factors that contribute to endothelial and vascular dysfunction, increased peripheral vascular resistance and worsening Renovascular Hypertension. (AU)