Vascular smooth muscle cells in low SYNTAX scores coronary artery disease exhibit proinflammatory transcripts and proteins correlated with IL1B activation. (January 2023)

• Record Type: Journal Article
• Authors: Dorajoo, Rajkumar; Ihsan, Mario Octavianus; Liu, Wenting; Lim, Hwee Ying; Angeli, Veronique; Park, Sung-Jin; Chan, Joyce M.S.; Lin, Xiao Yun; Ong, Mei Shan; Muniasamy, Umamaheswari; Lee, Chi-Hang; Gurung, Rijan; Ho, Hee Hwa; Foo, Roger; Liu, Jianjun; Kofidis, Theo; Lee, Chuen Neng; Sorokin, Vitaly A.
• Is Part Of: Atherosclerosis. Volume 365(2023)
• Page Start: 15
• Page End: 24
• Publication Date: 2023-01
• Subjects: Vascular smooth muscle cells -- IL1B -- SYNTAX score; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2022.12.005
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background and aims: The SYNTAX score is clinically validated to stratify number of lesions and pattern of CAD. A better understanding of the underlying molecular mechanisms influencing the pattern and complexity of coronary arteries lesions among CAD patients is needed. Methods: Human arterial biopsies from 49 patients (16 low-SYNTAX-score (LSS, <23), 16 intermediate-SYNTAX-score (ISS, 23 to 32) and 17 high-SYNTAX-score (HSS, >32)) were evaluated using Affymetrix GeneChip® Human Genome U133 Plus 2.0 microarray. The data were validated by Next-Generation Sequencing (NGS). Primary VSMC from patients with low and high SYNTAX scores were isolated and compared using immunohistochemistry, qPCR and immunoblotting to confirm mRNA and proteomic results. Results: The IL1B was verified as the top upstream regulator of 47 inflammatory DEGs in LSS patients and validated by another sets of patient samples using NGS analysis. The upregulated expression of IL1B was translated to increased level of IL1β protein in the LSS tissue based on immunohistochemical quantitative analysis. Plausibility of idea that IL1B in the arterial wall could be originated from VSMC was checked by exposing culture to proinflammatory conditions where IL1B came out as the top DEG (logFC = 7.083, FDR = 1.38 × 10 −114 ). The LSS patient-derived primary VSMCs confirmed higher levels of IL1B mRNA and protein. Conclusions: LSS patients could represent a group of patients where IL1B could play a substantial role in disease pathogenesis. The LSS group could represent a plausible cohort of patients for whom anti-inflammatory therapy could be considered. Graphical abstract: Image 1 Highlights: IL1B expression in the arterial wall correlates with the low-SYNTAX-score (LSS) pattern of coronary artery disease. IL1B was verified as the top upstream regulator in LSS samples, directly connected with 47 inflammatory differentially expressed genes (DEGs). IL1B was the top DEG under proinflammatory conditions in vascular smooth muscle cell (VSMC) culture. LSS patient-derived VSMCs showed higher levels of IL1B at the mRNA and protein levels compare to high-SYNTAX score. LSS patients with elevated levels of IL1B represent a specific group where inflammation could play a substantial role in disease pathogenesis.