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
Externally publishedYes

Fingerprint

Semaphorins
Thoracic Aortic Aneurysm
pathogenesis
sequencing
matrices
RNA
aorta
Enzymes
regulators
Association reactions
Tissue
arteries
Proteins
Degradation
vessels
enzymes
fragmentation
drugs
Pharmaceutical Preparations
degradation

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

Cite this

Mapping semaphorins and netrins in the pathogenesis of human thoracic aortic aneurysms. / Alebrahim, Dornazsadat; Nayak, Mangala; Ward, Alison; Ursomanno, Patricia; Shams, Rebecca; Corsica, Annanina; Sleiman, Rayan; Fils, Kissinger Hyppolite; Silvestro, Michele; Boytard, Ludovic; Hadi, Tarik; Gelb, Bruce; Ramkhelawon, Bhama.

In: International journal of molecular sciences, Vol. 20, No. 9, 2100, 01.05.2019.

Research output: Contribution to journalArticle

Alebrahim, D, Nayak, M, Ward, A, Ursomanno, P, Shams, R, Corsica, A, Sleiman, R, Fils, KH, 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, vol. 20, no. 9, 2100. https://doi.org/10.3390/ijms20092100
Alebrahim, Dornazsadat ; Nayak, Mangala ; Ward, Alison ; Ursomanno, Patricia ; Shams, Rebecca ; Corsica, Annanina ; Sleiman, Rayan ; Fils, Kissinger Hyppolite ; Silvestro, Michele ; Boytard, Ludovic ; Hadi, Tarik ; Gelb, Bruce ; Ramkhelawon, Bhama. / Mapping semaphorins and netrins in the pathogenesis of human thoracic aortic aneurysms. In: International journal of molecular sciences. 2019 ; Vol. 20, No. 9.
@article{6060f3a9b8bc4dbbb561ed20b141c12f,
title = "Mapping semaphorins and netrins in the pathogenesis of human thoracic aortic aneurysms",
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.",
keywords = "Aneurysms, Extracellular matrix, Netrins, Semaphorins, Vascular remodeling",
author = "Dornazsadat Alebrahim and Mangala Nayak and Alison Ward and Patricia Ursomanno and Rebecca Shams and Annanina Corsica and Rayan Sleiman and Fils, {Kissinger Hyppolite} and Michele Silvestro and Ludovic Boytard and Tarik Hadi and Bruce Gelb and Bhama Ramkhelawon",
year = "2019",
month = "5",
day = "1",
doi = "10.3390/ijms20092100",
language = "English (US)",
volume = "20",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "9",

}

TY - JOUR

T1 - Mapping semaphorins and netrins in the pathogenesis of human thoracic aortic aneurysms

AU - Alebrahim, Dornazsadat

AU - Nayak, Mangala

AU - Ward, Alison

AU - Ursomanno, Patricia

AU - Shams, Rebecca

AU - Corsica, Annanina

AU - Sleiman, Rayan

AU - Fils, Kissinger Hyppolite

AU - Silvestro, Michele

AU - Boytard, Ludovic

AU - Hadi, Tarik

AU - Gelb, Bruce

AU - Ramkhelawon, Bhama

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

KW - Aneurysms

KW - Extracellular matrix

KW - Netrins

KW - Semaphorins

KW - Vascular remodeling

UR - http://www.scopus.com/inward/record.url?scp=85065464484&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065464484&partnerID=8YFLogxK

U2 - 10.3390/ijms20092100

DO - 10.3390/ijms20092100

M3 - Article

C2 - 31035427

AN - SCOPUS:85065464484

VL - 20

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 9

M1 - 2100

ER -