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.
- MeSH
- apoptóza MeSH
- lidé MeSH
- ligandy MeSH
- nádorové biomarkery * MeSH
- nádory * etiologie metabolismus terapie MeSH
- produkty pokročilé glykace fyziologie MeSH
- proteiny S100 MeSH
- receptory imunologické * antagonisté a inhibitory fyziologie genetika MeSH
- signální transdukce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Konečné produkty pokročilé glykace (advanced glycation end products – AGEs) hrají významnou roli v patogenezi řady chronických onemocnění a jejich komplikací, především diabetických komplikací, aterosklerózy, komplikací chronických onemocnění ledvin a neurodegenerativních onemocnění. Tyto látky vznikají neenzymatickou glykací a jejich tvorba je potencována vlivem karbonylového stresu. AGEs tvoří heterogenní skupinu látek a patří mezi ně např. karboxymetyllyzin, pentozin, metylglyoxallyzin dimer, vesperlyzin, imidazolony a další. AGEs jednak modifikují proteiny a mění jejich fyzikální a chemické vlastnosti, jednak mají účinky zprostředkované přes receptory, z nichž nejznámější, ale ne jediný, je receptor RAGE (receptor pro konečné produkty pokročilé glykace). RAGE je receptor multiligandový, váže také HMGB1 (high mobility group box protein 1), S100 proteiny či amyloidové fibrily. Vazba ligand na tento receptor má za následek aktivaci řady signálních cest včetně indukce oxidačního stresu a aktivace nukleárního faktoru κB a následnou prozánětlivou odpověď v závislosti na buněčném typu. AGEs a RAGE se spolu s dalšími mechanizmy – hexosaminovou cestou, polyolovou cestou, poruchou metabolizmu lipidů, aktivací proteinkinázy C, oxidačním stresem a zánětlivou reakcí spoluúčastní v patogenezi diabetických komplikací. Terapeuticky je možné snižovat endogenní tvorbu AGEs, ovlivnit přísun AGEs do organizmu stravou a jejich absorpci ve střevě či stimulovat jejich degradaci. Klíčová slova: AGEs – diabetes mellitus – karbonylový stres – konečné produkty pokročilé glykace – oxidační stres – RAGE – receptor pro AGEs – sRAGE – zánět
Advanced glycation end products (AGEs) play an important role in the pathogenesis of chronic diseases and their complications, especially diabetic complications, atherosclerosis, complications of chronic kidney diseases and neurodegenerative diseases. These substances are formed via non-enzymatic glycation and their formation is potentiated in case of carbonyl stress. AGEs are represented by a heterogeneous group of compounds, e.g. carboxymethyllysine, pentosine, methylglyoxallysin dimer, vesperlysine, imidazolones etc. AGEs can modify proteins and so change their physical and chemical properties and can act also via specific receptors, among them RAGE (receptor for advanced glycation end products) is the best known but not the unique one. RAGE is a multiligand receptor capable to bind also HMGB1 (high mobility group box protein 1), S100 proteins or amyloid fibrils. RAGE – ligand interactions results to activation of a variety of signaling pathways including oxidative stress and activation of nuclear factor κB and subsequent proinflammatory response depending on the cell type. AGEs and RAGE together with further mechanisms – hexosamine pathway, polyol pathway, lipid metabolism disorder, activation of proteinkinase C, oxidative stress and inflammatory reaction take part in the pathogenesis of diabetic complications. Terapeuticaly it is possible to decrease endogenous formation of AGEs, influence the AGEs intake to the organism and their absorption in the intestine or stimulate their degradation. Key words: AGEs – advanced glycation end-products – carbonyl stress – diabetes mellitus – inflammation – oxidative stress – RAGE – receptor for AGEs – sRAGE
- Klíčová slova
- karbonylový stres, sRAGE, receptor pro AGEs,
- MeSH
- diabetes mellitus etiologie MeSH
- glykovaný hemoglobin fyziologie MeSH
- lidé MeSH
- oxidační stres fyziologie MeSH
- produkty pokročilé glykace * fyziologie metabolismus škodlivé účinky MeSH
- receptory imunologické * biosyntéza MeSH
- zánět MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- biologické modely MeSH
- diabetes mellitus 1. typu komplikace krev metabolismus MeSH
- diabetes mellitus 2. typu komplikace krev metabolismus MeSH
- kardiovaskulární nemoci etiologie krev metabolismus MeSH
- komplikace diabetu metabolismus prevence a kontrola MeSH
- krevní glukóza metabolismus MeSH
- lidé MeSH
- metabolické sítě a dráhy fyziologie MeSH
- oxidační stres fyziologie MeSH
- produkty pokročilé glykace fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- souhrny MeSH
Patients treated for knee disorders were included in this study. They were examined clinically (Lequesne and Tegner scores) and by standard X-ray investigation. Patients underwent a surgical procedure, either arthroscopy or knee replacement. At the initial phase of surgery, a sample of cartilage was taken for laboratory examination. Progression of the disorder and the clinical examination was correlated with the actual state of the cartilage using a novel fluorescence approach. The intrinsic fluorescence of cartilages was shown as a suitable and sensitive method for detection of the actual state of cartilages because the correlation with X-ray examination and clinical status was found. Intrinsic fluorescence properties of cartilages from patients with chondropathy and osteoarthritis were described and found to be age-dependent. We also observed a higher concentration of advanced glycation end products due to inflammatory and/or degenerative processes in the cartilage. In addition, acute pathological changes due to diseases such as meniscal lesions or anterior cruciate ligament rupture caused a significant increase of formation of advanced glycation end products even in the group of young patients. In fact, such an observation could be crucial and important for the detection of knee conditions suspected of early meniscal and/or ACL lesions especially among young patients.
- MeSH
- finanční podpora výzkumu jako téma MeSH
- fluorescence MeSH
- kolenní kloub fyziologie metabolismus patologie MeSH
- lidé MeSH
- nemoci chrupavky komplikace metabolismus patologie MeSH
- produkty pokročilé glykace fyziologie metabolismus škodlivé účinky MeSH
- rentgendiagnostika metody využití MeSH
- totální endoprotéza kolene využití MeSH
- Check Tag
- lidé MeSH
- MeSH
- dialýza ledvin škodlivé účinky MeSH
- finanční podpora výzkumu jako téma MeSH
- lidé MeSH
- produkty pokročilé glykace fyziologie MeSH
- renální insuficience patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- kongresy MeSH
- MeSH
- diabetes mellitus komplikace krev patofyziologie MeSH
- finanční podpora výzkumu jako téma MeSH
- lidé MeSH
- oxidační stres genetika MeSH
- produkty pokročilé glykace fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
