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Distinct gene expression profiles associated with Notch ligands Delta-like 4 and Jagged1 in plaque material from peripheral artery disease patients: a pilot study.
Distinct gene expression profiles associated with Notch ligands Delta-like 4 and Jagged1 in plaque material from peripheral artery disease patients: a pilot study.
- Source :
-
Journal of translational medicine [J Transl Med] 2017 May 04; Vol. 15 (1), pp. 98. Date of Electronic Publication: 2017 May 04. - Publication Year :
- 2017
-
Abstract
- Background: The lack of early diagnosis, progression markers and effective pharmacological treatment has dramatic unfavourable effects on clinical outcomes in patients with peripheral artery disease (PAD). Addressing these issues will require dissecting the molecular mechanisms underlying this disease. We sought to characterize the Notch signaling and atherosclerosis relevant markers in lesions from femoral arteries of symptomatic PAD patients.<br />Methods: Plaque material from the common femoral, superficial femoral or popliteal arteries of 20 patients was removed by directional atherectomy. RNA was obtained from 9 out of 20 samples and analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR).<br />Results: We detected expression of Notch ligands Delta-like 4 (Dll4) and Jagged1 (Jag1), of Notch target genes Hes1, Hey1, Hey2, HeyL and of markers of plaque inflammation and stability such as vascular cell adhesion molecule 1 (VCAM1), smooth muscle 22 (SM22), cyclooxygenase 2 (COX2), Bcl2, CD68 and miRNAs 21-5p, 125a-5p, 126-5p,146-5p, 155-5p, 424-5p. We found an "inflamed plaque" gene expression profile characterized by high Dll4 associated to medium/high CD68, COX2, VCAM1, Hes1, miR126-5p, miR146a-5p, miR155-5p, miR424-5p and low Jag1, SM22, Bcl2, Hey2, HeyL, miR125a-5p (2/9 patients) and a "stable plaque" profile characterized by high Jag1 associated to medium/high Hey2, HeyL, SM22, Bcl2, miR125a and low Dll4, CD68, COX2, VCAM1, miR126-5p, miR146a-5p, miR155-5p, miR424-5p (3/9 patients). The remaining patients (4/9) showed a plaque profile with intermediate characteristics.<br />Conclusions: This study reveals the existence of a gene signature associated to Notch activation by specific ligands that could be predictive of PAD progression.
- Subjects :
- Adaptor Proteins, Signal Transducing
Aged
Animals
Calcium-Binding Proteins
Cholesterol metabolism
Female
Follow-Up Studies
Humans
Inflammation pathology
Ligands
Male
MicroRNAs genetics
MicroRNAs metabolism
Myocytes, Smooth Muscle metabolism
Pilot Projects
RNA, Messenger genetics
RNA, Messenger metabolism
Rats
Receptors, Notch metabolism
Signal Transduction genetics
Intercellular Signaling Peptides and Proteins metabolism
Jagged-1 Protein metabolism
Peripheral Arterial Disease genetics
Peripheral Arterial Disease pathology
Plaque, Atherosclerotic pathology
Transcriptome
Subjects
Details
- Language :
- English
- ISSN :
- 1479-5876
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 28472949
- Full Text :
- https://doi.org/10.1186/s12967-017-1199-3