SENESCENCE AND DYSFUNCTION OF THE PERIVASCULAR ADIPOSE TISSUE: EFFECTS PROMOTED BY ANTICANCER DRUGS

• Grant number: 25/11336-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2025
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Eliana Hiromi Akamine
• Grantee: Ana Clara Romero Almeida
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cardiovascular diseases and cancer are both the main causes of mortality and morbidities in the world. Anticancer therapies, although provide a good prognosis to oncologic patients, promote several adverse effects, including cardiovascular toxicity, affecting the endothelial cells and the vascular smooth muscle cells (VSMCs). In this way, it is observed that these anticancer drugs lead to the development of cardiovascular diseases, such as arterial hypertension and atherosclerosis. Perivascular adipose tissue (PVAT) may be another target of anticancer therapies, since it surrounds the blood vessels and helps in vascular function regulation, so that your dysfunction causes a change of its secretome, affecting VSMCs, with increase in contractile response and proliferation and migration capacity. However, there is no research about the effects of anticancer drugs on PVAT. Anticancer therapies induce senescence on both tumoral and non-tumoral cells. Cellular senescence is a persistent state of the cell, in which there is cellular cycle arrest and changes in its profile of protein expression and secretion, affecting the adjacent cells. Senescence can occur on both VSMCs and on endothelial cells, affecting their functions; however, it is not known whether PVAT senescence is associated with its dysfunction, and even whether anticancer therapies induce senescence on PVAT cells. Therefore, this project intends to evaluate whether anticancer drugs induce senescence and dysfunction on PVAT. In addition, the influence of PVAT treated with anticancer drugs on VSMC proliferation will also be evaluated.