| Abstrakt: |
OBJECTIVE: Carotid artery stenosis (CAS) accounts for 30% of all strokes. Several factors, including plaque biology, intraplaque hemorrhage, and ulcerations, are related to CAS symptoms. However, these can also observe in asymptomatic patients whose stenosis degrees correlate with stroke, but carotid stenoses progress to occlusion without any stroke-related symptoms. Thus, asymptomatic patients do not benefit much from surgery compared to symptomatics. Therefore, more studies are needed for molecular mechanisms underlying the CAS symptoms to perform a multidisciplinary assessment for better clinical management of CAS. We performed RNA transcriptome analysis in the plaques of CAS patients to discriminate asymptomatics from symptomatic ones, even in the presence of ulceration. Methods: Eight CAS patients, 50% (n=4) of asymptomatic, were included in the study. Stenosis degree and plaque ulceration were determined radiologically before CAE. Then, total RNAs were isolated from plaques, and quality confirmations were performed. AmpliSeq transcriptome human gene expression panel was used for transcriptome analysis on an IonGeneStudioTMS5 sequencer. AmpliSeq data were analyzed using CLC workbench and IonReporter. Differentially expressed genes (DEGs) were selected based on p<0.001&log2FC between asymptomatic and symptomatic groups. Results: The mean age of the patients was 68.9±6.7 years. 25% (n=2) were female, and 75% (n=6) were male. The degree of stenosis was 70% and greater in all patients. While 100% of symptomatic patients (n=4) have ulcerated plaque, 50% of asymptomatic ones (n=2) showed ulceration. Totally, 2,361 DEGs were detected (p<0.001, log2FC±1.5-fold). From 250 transcripts showing the most variation, the most significant ones were selected based on the gene representation heatmap and compared between asymptomatic and symptomatic groups. In asymptomatics, 116 and 32 DEGs were upregulated and downregulated, respectively. Enrichment analysis showed that the transcripts with the most significant upregulation, including NPR3 (10.46-fold), BMP6 (16.86-fold), and ITLN1 (34.87-fold), mainly play a role in vascular remodeling and immune response. The transcripts to be downregulated, including SLC1A3 (6.64-fold), SLC37A2 (6.67-fold), and ACP5 (7.68-fold), have a function in glucose metabolism and immune response. When the patients with ulcerated plaques were compared, 73 DEGs were upregulated, mainly responsible for calcification and cell adhesion, FHL5 (5.64-fold), TMEM47 (4.21-fold), and OMD (3.49-fold), in the asymptomatic group. However, 33 DEGs were significantly downregulated, including PTGDS (4.79-fold), SLC37A2 (2.98-fold), and CHICL3 (4.2-fold), which act in lipid and glucose metabolism, tissue damage, and remodeling. Conclusions: Our results suggest that increased plaque calcification, vascular remodeling shifting, and altered glucose metabolism contribute to distinguishing asymptomatic and symptomatic CAS patients. [ABSTRACT FROM AUTHOR] |
