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

Abstract

Background and aimsThe 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. MethodsHuman 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. ResultsThe 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. ConclusionsLSS 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.