Cholesterol Crystals as the Main Trigger of Interleukin-6 Production through Innate Inflammatory Response in Human Spontaneously Ruptured Aortic Plaques

Aim: This study aimed to clarify whether cholesterol crystals (CCs) are the main trigger of innate inflammation in human spontaneously ruptured aortic plaques (SRAPs). Methods: This study included 260 SRAPs collected during nonobstructive general angioscopy (NOGA) from 126 patients with confirmed or suspected coronary artery disease. Interleukin (IL)-6 levels in SRAPs were measured. IL-6 levels in the Valsalva sinus and femoral or brachial arteries were measured. IL-6 ratios (the IL-6 level in SRAPs and arteries divided by the IL-6 level at the Valsalva sinus at the beginning of the aorta) were calculated. Quantitative analysis of CCs was performed from SRAPs. The correlation between the count of CCs and IL-6 levels in SRAPs and that between the counts of CCs and IL-6 ratios in SRAPs were analyzed. Results: The IL-6 levels in SRAPs were 3.4 [2.1, 7.2] pg/mL, and the IL-6 ratio (median [interquartile range]) in SRAPs was 1.10 [1.00, 1.26]. CCs were detected in 94 of 260 SRAPs (36%). The count of CCs was 11,590 (95% confidence interval, 2,386–30,113) per 10 mL in CC-positive samples. There was a moderate correlation between the counts of CCs and IL-6 ratios in SRAPs (r=0.49, r＜0.0001), whereas there was no correlation between the count of CCs and IL-6 levels in SRAPs. The IL-6 ratios of the brachial and femoral arteries were 1.06 (95% CI, 0.99–1.20) and 1.11 (95% CI, 1.04–1.20), respectively. Conclusions: CC is the main trigger of IL-6 production through innate inflammatory response in human SRAPsin situ.