Endothelial glycocalyx in salivary glands: from morphogenesis to menopause

• Grant number: 25/15595-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Silvia Vanessa Lourenço
• Grantee: Letícia Ferrari Cossaros
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 22/12807-5 - Xerostomia in pre and post-menopause and its interface with women's oral health: investigation from bench to bedside, AP.TEM

Abstract

The formation and function of human salivary glands depend on coordinated morphogenetic events and dynamic interactions between the epithelium, mesenchyme, and the vascular microenvironment. Saliva production is a complex process that begins in the acini through transcellular and paracellular pathways and is later modulated in the ducts under the influence of neuroendocrine, paracrine, and autocrine signals. An essential component of this process is the microvasculature. In this context, the endothelial glycocalyx (EG) plays a key role. The EG is a structure composed of proteoglycans, glycosaminoglycans, and glycoproteins that lines the luminal surface of blood vessels and regulates vascular permeability, mechanotransduction, inflammation, oxidative stress, and cell adhesion. The integrity of the EG may be fundamental to the functional balance of salivary glands, particularly due to its role in vascularization and the supply of fluids required for salivary secretion. Studies indicate that during aging, the EG undergoes degenerative changes associated with decreased expression of components such as glypican-1 and reduced nitric oxide (NO) availability. Additionally, there is growing evidence suggesting that female sex hormones-especially estrogen and progesterone-modulate the composition and function of the EG, potentially impacting glandular physiology. During menopause, the decline in hormone levels may contribute to salivary gland dysfunction, promoting the development of xerostomia. This condition can be further exacerbated by comorbidities common in this life stage, such as diabetes, Sjögren's syndrome, and rheumatoid arthritis. Although studies report beneficial effects of hormone therapy on dry mouth symptoms, the underlying mechanisms-particularly the interaction between membrane channels such as aquaporins and the EG-are to be unraveled. In this context, investigating the role of the endothelial glycocalyx across the lifespan, from salivary gland embryogenesis to senescence, may provide valuable insights into the pathophysiology of hormone-related salivary dysfunction.