Nejvíce citovaný článek - PubMed ID 26631850
Soluble receptor for advanced glycation end products and increased aortic stiffness in the general population
Stiffening of large arteries, clinically manifesting as increased aortic pulse wave velocity (PWV), is an inevitable outcome of aging. Among other mechanisms, impaired glucose metabolism plays an important role, leading to the deposition of advanced glycation end products (AGEs). This process is counterbalanced by the circulating soluble receptor for AGEs (sRAGE). We investigated the association between arterial stiffness on one side and multiple circulating biomarkers and the degree of skin deposition of AGEs on the other. In a cross-sectional design, 867 participants based on a general population sample (Czech post-MONICA studies) were examined. PWV was measured by SphygmoCor device (AtCor Medical Ltd.), while skin AGEs were measured using a dedicated autofluorescence method (AGE Reader mu®). To quantify the circulating status of AGEs, carboxymethyl lysine (CML) and sRAGE concentrations were assessed by ELISA, along with conventional glucose metabolism indicators. When analyzing the whole sample using multiple linear or logistic regression models and after adjustment for potential covariates, a significant association with PWV was found for fasting glycemia, HbA1c, sRAGE, skin AGEs, and the skin AGE-to-sRAGE ratio. Among these parameters, stepwise models identified the strongest association for the skin AGEs and AGE-to-sRAGE ratio, and this was also true when diabetic subjects were excluded. In contrast, neither CML nor its ratio relative to sRAGE showed any association with arterial stiffness. In conclusion, skin AGEs along with their ratio relative to sRAGE were closely associated with arterial stiffness and is a better indicator of the current status of deposited AGEs than other relevant factors.
- Klíčová slova
- AGEs, Carboxymethyl lysine, Glucose metabolism, Pulse wave velocity, SRAGE,
- MeSH
- biologické markery krev MeSH
- fluorescence MeSH
- fyziologie kůže MeSH
- lidé MeSH
- produkty pokročilé glykace * fyziologie MeSH
- průřezové studie MeSH
- reprodukovatelnost výsledků MeSH
- tuhost cévní stěny * fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- produkty pokročilé glykace * MeSH
Circulating levels of soluble receptor for advanced glycation end-products (sRAGE) have been suggested to have a protective role in neutralizing advanced glycation end-products (AGEs) and their pathological effects on vessel walls. We aimed to investigate the association between the circulating concentration of sRAGE and the dynamics of arterial wall stiffening as a manifestation of vascular aging in the general population. In a prospective cohort study, we longitudinally followed 530 general-population-based subjects (subsample of Czech post-MONICA study). Aortic pulse wave velocity (PWV) was measured twice (at baseline and after ~8 years of follow-up) using a SphygmoCor device (AtCor Medical Ltd), and the intraindividual change in PWV per year (∆PWV/year) was calculated. Concentrations of sRAGE were assessed at baseline by ELISA (R&D Systems). The average ∆PWV/year significantly decreased across the sRAGE quintiles (p = 0.048), and a drop by one sRAGE quintile was associated with an ~21% increase in the relative risk of accelerated age-dependent stiffening (∆PWV/year ≥ 0.2 m/s). Subjects in the bottom quintile of sRAGE (<889.74 pg/mL) had a fully adjusted odds ratio of accelerated stiffening of 1.72 (95% CI: 1.06-2.79), p = 0.028, while those with high sRAGE concentrations (≥1695.2 pg/mL) showed the opposite effect [odds ratio 0.55 (95% CI: 0.33-0.90), p = 0.017]. In conclusion, the circulating status of sRAGE independently influenced the individual progression of arterial stiffness over time. This finding strongly supports the hypothesis that high sRAGE has a protective role against vascular aging.
- Klíčová slova
- AGEs, General population, Prospective study, Pulse wave velocity, Vascular aging, sRAGE,
- MeSH
- analýza pulzové vlny MeSH
- dospělí MeSH
- krevní tlak fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- longitudinální studie MeSH
- prospektivní studie MeSH
- receptor pro konečné produkty pokročilé glykace krev MeSH
- senioři MeSH
- stárnutí metabolismus MeSH
- tuhost cévní stěny fyziologie MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- receptor pro konečné produkty pokročilé glykace MeSH