Tenascin-X deficiency and vascular aspects in classical-like Ehlers-Danlos syndrome (clEDS)

• Grant number: 23/14854-3
• Support Opportunities: Scholarships abroad - Research
• Start date: February 01, 2024
• End date: June 30, 2024
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Luciano de Figueiredo Borges
• Grantee: Luciano de Figueiredo Borges
• Host Investigator: Valcourt Ulrich
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Institution abroad: Université Claude Bernard Lyon 1, France

Abstract

Tenascin X (TNX) was the first non-collagenous molecule of the extracellular matrix that has been shown to be related to Classic Ehlers-Danlos Syndrome (clEDS), a group of heterogeneous disorders characterized by alterations in the biomechanical properties of connective tissues. Patients with clEDS are notably characterized by vascular fragility, which ranges from spontaneous bruising to hemorrhagic complications. The pathological mechanisms that explain vascular fragility in the absence of TNX have never been explored. The VASCLEDS project aims to determine the role played by TNX in vascular architecture and function. In a mouse model of clEDS, we will characterize the mechanical, vasomotor and structural vascular defects caused by TNX deficiency. We will also evaluate the involvement of telocytes in maintaining vascular integrity. Finally, we will identify the molecular and cellular factors involved in vascular fragility and explore the role of TNX in the development of thoracic aortic aneurysms and dissections in mice and humans, using complementary in vivo, ex vivo and in vitro approaches.