Study of Annexin A1 in Experimental Diabetic Cardiomyopathy: Inflammatory aspects and Estrogen Depletion.

• Grant number: 24/14322-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2025
• End date: November 30, 2027
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Cristiane Damas Gil
• Grantee: Renata Ramos Vieira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Diabetes mellitus (DM) is considered a chronic disease that affects thousands of people and is identified as a risk factor for coronary heart disease. Moreover, it leads to hormonal changes during menopause, where there is a decline in estradiol levels, which increases cardiovascular risk. In this context, Annexin A1 (AnxA1) stands out as an anti-inflammatory protein that, in addition to mediating various stages of the inflammatory response, has a cardioprotective role. However, its role in cardiac dysfunction caused by DM has not been established. Therefore, the overall objective of this study is to investigate the role of the AnxA1 protein in diabetic cardiomyopathy induced in menopausal female mice. After inducing menopause by ovariectomy in 9-week-old female mice, DM1 will be induced by intraperitoneal injection (for 5 consecutive days) of STZ (65 mg/kg) in wild-type (WT) C57BL/6 animals and AnxA1 knockout (AnxA1-/-) animals. In sham animals, only vehicle injections (0.1 M sodium citrate buffer, pH 4.5) will be administered. In the 4th, 8th, 12th, and 16th weeks, the animals will be weighed, and circulating glucose levels will be measured. Histopathological analysis, immunohistochemical analysis, and Western Blotting of AnxA1, FPR2, and estradiol receptors will be performed on the heart tissue. In the plasma and heart tissue homogenate, cytokine analysis (IL-1¿, IL-4, IL-6, IL-10, IL-17, KC/GRO/CINC-1/CXCL1, MCP-1/CCL2, and TNF-¿) and proteins related to cardiovascular diseases, including matrix metalloproteinase-9 proform (pMMP9), soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule (sICAM-1), and platelet endothelial cell adhesion molecule (PECAM-1), will be conducted. Finally, a functional heart assay will be performed through electrocardiogram. The studies will contribute to advancing the understanding of the effects of estrogen and Annexin A1 on cardiac biology associated with diabetes.