Skin autofluorescence is associated with plasma levels of matrix metalloproteinases in subjects without overt atherosclerosis

Background: Advanced glycation end products (AGEs) may promote arterial matrix remodeling via the receptor for AGEs (RAGE) signaling. Skin autofluorescence estimates tissue AGE burden. We examined whether skin autofluorescence relates to circulating matrix metalloproteinases (MMPs) and subclinical carotid atherosclerosis in asymptomatic adults. Methods: In a cross-sectional cohort of 262 asymptomatic adults, skin autofluorescence was measured with the AGE Reader. Plasma concentrations of MMP-3, MMP-9, tissue inhibitor of metalloproteinases-1 (TIMP-1), high-sensitivity C-reactive protein (hsCRP), and soluble RAGE (sRAGE) were measured by enzyme-linked immunosorbent assay (ELISA). Carotid intima-media thickness (IMT) and plaque burden were quantified by ultrasound. Associations between skin autofluorescence and biomarkers were tested using multivariable linear regression with prespecified covariates; biomarker coefficients were scaled per 10 ng/mL (hsCRP per 1 mg/L). Results: Skin autofluorescence correlated with MMP-3, MMP-9, TIMP-1, hsCRP, and IMTmean (all p < 0.001) and with IMTmax (p = 0.008), but not with sRAGE. In multivariable models, skin autofluorescence remained independently associated with MMP-3 (p < 0.001), MMP-9 (p = 0.05), and TIMP-1 (p = 0.049), but not hsCRP (p = 0.41). Plaque-positive participants had higher skin autofluorescence, MMP-9, and hsCRP than those without plaques; MMP-9 and hsCRP were also higher in the high- versus intermediate-plaque group, whereas MMP-3 and TIMP-1 did not differ. Conclusions: In asymptomatic adults, higher skin autofluorescence is independently associated with circulating MMP-3, MMP-9, and TIMP-1, and with early carotid atherosclerosis markers. Findings support a link between tissue glycation and arterial matrix remodeling and suggest that skin autofluorescence plus MMP-9 may offer a practical, noninvasive approach for early vascular risk stratification.