Emilin-1 in the cardiovascular system of zebrafish and in human aorta biopsies

Emilin-1 is an extracellular matrix (ECM) glycoprotein belonging to the EMILINS/Multimerin family, found in elastic tissues like heart, blood vessels, lungs and dermis. It plays a key role in elastogenesis, cell adhesion, maintenance of vascular cell morphology and modulation of blood pressure homeostasis. To explore Emilin-1’s role in cardiovascular health, we used Danio rerio as an in vivo model, selected for its easy genetic manipulability and cardiovascular similarities to humans. Using CRISPR- Cas9 technology, we generated emilin-1a and emilin-1b knockout zebrafish lines. The double knockout zebrafish exhibited reduced survival rates during early development. Fluorescent imaging of vascular structures showed altered vessel morphology, an increase in diameter of the dorsal aorta (DA), posterior cardinal vein (PVC) and bulb, highlighting Emilin-1’s role in angiogenesis and vascular maintenance. Cardiac function assessments using pyHeart4Fish indicated increased cardiac size and reduced efficiency in the knockout blood circulation. Aorta samples from patients with Emilin-1 mutations were analyzed through immunofluorescence and protein assays, revealing altered ECM organization around elastic fibers and smooth muscle layers. Western Blot analysis of Emilin-1 and related proteins revealed the impact of mutations on vascular structure. This research deepens our understanding of Emilin-1's role in cardiovascular health and its significance in vascular diseases.