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April 27, 2026Journal of Cellular and Molecular MedicineOpen Access

Dysregulated Sheddase Signalling as a Molecular Driver of Plaque Instability Revealed by Integrative Transcriptomics

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Key result

Unstable plaques display ~4800 differentially expressed genes vs stable plaques, driven by sheddase upregulation.

  • P<0.05
  • n=4

Population

Human carotid atherosclerotic plaque samples from 4 patients obtained from the Gene Expression Omnibus…

Comparison

Transcriptomic profiling of unstable plaques vs Transcriptomic profiling of stable plaques

Design

Preclinical

Authors

AAAlaa G. AlahmadiUniversity of JeddahHAHind A. AlkhatabiUniversity of JeddahRAReem M AlotibiUniversity of Jeddah

Discussion

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Implication

Integrative transcriptomics reveals that the sheddase pathway and extracellular matrix degradation are key molecular drivers of atherosclerotic plaque instability, offering potential new therapeutic targets.

Key Points

  • This research aims to explore the differences in gene expressions between stable and unstable atherosclerotic plaques to identify molecular drivers of plaque instability.
  • RNA sequencing was performed on human carotid atherosclerotic plaque samples from four patients.
  • Differentially expressed genes (DEGs) were identified through data normalization and analysis using multiple bioinformatics tools.
  • Integrative transcriptomic analysis highlighted significant pathways involved in plaque instability.
  • 4792 DEGs were identified in unstable plaques with a p-value cutoff of <0.05.
  • The sheddase pathway was significantly upregulated, along with collagen degradation and MMP activation in unstable plaques.
  • Downregulation of MMP inhibition and smooth muscle contraction pathways was also observed.

Study Design

Type

Observational (n=4)

Structured PICO

P
Population
4 patients providing human carotid atherosclerotic plaque samples dissected into stable and unstable regions for RNA sequencing.
E
Exposure
Transcriptomic profiling (RNA-seq) of unstable plaques
C
Comparator
Transcriptomic profiling of stable plaques
O
Outcome
Differentially expressed genes (DEGs) and enriched molecular pathwayssurrogate

Main Result

p-value: p=< 0.05

Integrative transcriptomics reveals that the sheddase pathway and extracellular matrix degradation are key molecular drivers of atherosclerotic plaque instability, offering potential new therapeutic targets.

Cite This Study

Alahmadi et al. (2026) conducted an observational in Atherosclerosis (n=4). Unstable plaque regions vs. Stable plaque regions was evaluated on Differentially expressed genes (DEGs) (p=< 0.05). Unstable atherosclerotic plaques exhibited 4792 differentially expressed genes compared to stable plaques (P<0.05), with the sheddase pathway identified as a significantly upregulated driver.

synapsesocial.com/papers/69eefde9fede9185760d4ab4https://doi.org/10.1111/jcmm.71136
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