Platelet RNA-Seq Reveals Genes Associated with Carotid Intima-Media Thickness: A Cross-Sectional Study
Zhanfei Tan1, Fan Guo2,3, Jiaming Gao2,3
1Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Insights
This study identified four key platelet genes (ITGA2B, TGFB1, PF4, GP9) associated with atherosclerosis progression. These genes show potential as novel biomarkers for diagnosing and predicting atherosclerosis risk.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Biomarker Discovery
Background:
- Atherosclerosis (AS) risk is linked to platelet characteristics, but their precise role is unclear.
- Understanding platelet function is crucial for AS pathogenesis and diagnosis.
Purpose of the Study:
- Identify platelet gene expression differences in patients with and without AS.
- Discover novel platelet-derived biomarkers for AS diagnosis and risk assessment.
Main Methods:
- Cross-sectional study comparing AS patients and healthy controls (N).
- Carotid ultrasound used to measure intima-media thickness (IMT) for AS definition.
- Platelet RNA sequencing (RNA-seq) performed on extracted plasma platelets.
Main Results:
- Identified 784 differentially expressed genes in AS patients, including 141 downregulated and 643 upregulated.
- Gene Ontology analysis revealed significant enrichment in blood coagulation pathways.
- Weighted correlation network analysis identified four hub genes (ITGA2B, TGFB1, PF4, GP9) correlated with IMT.
Conclusions:
- Elevated ITGA2B, TGFB1, PF4, and GP9 levels showed moderate correlations with increased IMT.
- These genes are potential predictive biomarkers for atherosclerosis.
Background:
Although the association between platelet characteristics and the risk of developing atherosclerosis (AS) has been acknowledged, the specific role of platelets in AS development and progression remains unclear. Therefore, the aim of this study was to identify platelet characteristics in patients with and without AS to enhance the understanding of their pathophysiological functions and discover more sensitive biomarkers for AS diagnosis.
Methods:
We conducted a cross-sectional study involving AS patients and healthy controls (N). Based on the Chinese guidelines for diagnosing carotid and vertebral artery AS and the 2010 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines, we defined AS using carotid ultrasound to measure intima-media thickness (IMT). General information, including sex, age, height, and weight, was collected upon enrollment. A series of examinations, including physical exams, serum lipid profiles, blood glucose tests, liver and kidney function tests, platelet aggregation assays, and carotid artery ultrasounds, was performed. Platelets were extracted from plasma for RNA-seq analysis.
Results:
No statistically significant differences in age, sex, body mass index, or blood pressure were observed between the groups. Total triglyceride, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, red blood cell count, hemoglobin concentration, cholesterol levels, and carotid IMT were significantly greater, and vascular endothelial function was significantly lower in the AS group than in the N group. Using RNA-seq, we identified 784 differentially expressed genes-141 downregulated and 643 upregulated-with Gene Ontology enrichment showing significant associations with blood coagulation pathways, among others. Weighted correlation network analysis revealed four hub genes related to IMT: Integrin Subunit Alpha 2b (ITGA2B), Transforming Growth Factor Beta 1 (TGFB1), Platelet Factor 4 (PF4) , and Glycoprotein IX Platelet (GP9) .
Conclusion:
Our findings indicate moderate correlations of elevated ITGA2B ( r = 0.327, p = 0.004), TGFB1 ( r = 0.362, p = 0.001), PF4 ( r = 0.240, p = 0.038), and GP9 ( r = 0.302, p = 0.008) levels with increased IMT, suggesting that these genes may serve as predictive biomarkers for AS.
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