Mapping semaphorins and netrins in the pathogenesis of human thoracic aortic aneurysms

Dornazsadat Alebrahim, Mangala Nayak, Alison Ward, Patricia Ursomanno, Rebecca Shams, Annanina Corsica, Rayan Sleiman, Kissinger Hyppolite Fils, Michele Silvestro, Ludovic Boytard, Tarik Hadi, Bruce Gelb, Bhama Ramkhelawon

Research output: Contribution to journalArticle

Abstract

Thoracic aortic aneurysm (TAA) is a complex life-threatening disease characterized by extensive extracellular matrix (ECM) fragmentation and persistent inflammation, culminating in a weakened aorta. Although evidence suggests defective canonical signaling pathways in TAA, the full spectrum of mechanisms contributing to TAA is poorly understood, therefore limiting the scope of drug-based treatment. Here, we used a sensitive RNA sequencing approach to profile the transcriptomic atlas of human TAA. Pathway analysis revealed upregulation of key matrix-degrading enzymes and inflammation coincident with the axonal guidance pathway. We uncovered their novel association with TAA and focused on the expression of Semaphorins and Netrins. Comprehensive analysis of this pathway showed that several members were differentially expressed in TAA compared to controls. Immunohistochemistry revealed that Semaphorin4D and its receptor PlexinB1, similar to Netrin-1 proteins were highly expressed in damaged areas of TAA tissues but faintly detected in the vessel wall of non-diseased sections. It should be considered that the current study is limited by its sample size and the use of internal thoracic artery as control for TAA for the sequencing dataset. Our data determines important neuronal regulators of vascular inflammatory events and suggest Netrins and Semaphorins as potential key contributors of ECM degradation in TAA.

Original languageEnglish (US)
Article number2100
JournalInternational journal of molecular sciences
Volume20
Issue number9
DOIs
StatePublished - May 1 2019

Keywords

  • Aneurysms
  • Extracellular matrix
  • Netrins
  • Semaphorins
  • Vascular remodeling

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    Alebrahim, D., Nayak, M., Ward, A., Ursomanno, P., Shams, R., Corsica, A., Sleiman, R., Fils, K. H., Silvestro, M., Boytard, L., Hadi, T., Gelb, B., & Ramkhelawon, B. (2019). Mapping semaphorins and netrins in the pathogenesis of human thoracic aortic aneurysms. International journal of molecular sciences, 20(9), [2100]. https://doi.org/10.3390/ijms20092100