Objective-The receptor for advanced glycation end products (RAGE) is a cell surface receptor whose signaling pathway has been implicated in atherogenesis. RAGE has an endogenous secretory receptor form, called soluble RAGE (sRAGE), that could exert antiatherogenic effects by acting as a decoy. We sought to determine whether a decreased plasma level of sRAGE could be independently associated with the prevalence of coronary artery disease (CAD) in nondiabetic men. Methods and Results-Plasma levels of sRAGE were determined in 328 nondiabetic male patients with angiographically proved CAD and in 328 age-matched healthy controls.
See page 879The receptor for advanced glycation end products (RAGE) is a transmembrane receptor of the immunoglobulin superfamily that engages diverse ligands relevant to the pathogenesis of atherosclerosis 4 and that is highly hyperexpressed at sites of vascular pathology. 5 Numerous lines of evidence indicate that ligand-triggered RAGE-dependent cellular activation results in several deleterious effects, including activation of nuclear factor-B, increased expression of cytokines and adhesion molecules, and induction of oxidative stress. 6 -8 One class of RAGE ligands includes glycoxidation products, termed advanced glycation end products (AGEs), which accumulate at an extremely high rate in the diabetic state. 9,10
Regular exercise has multi-system anti-aging effects. Here we summarize how exercise impacts the major hallmarks of aging. We propose that, besides searching for novel pharmaceutical targets of the aging process, more research efforts should be devoted to gaining insights into the molecular mediators of the benefits of exercise and to implement effective exercise interventions for elderly people.
Macrophage activation can be modulated by biomaterial topography according to the biological scale (micrometric and nanometric range). In this study, we investigated the effect of fiber diameter and fiber alignment of electrospun poly(L-lactic) (PLLA) scaffolds on macrophage RAW 264.7 activation and secretion of proinflammatory cytokines and chemokines at 24 h and 7 days. Macrophages were cultured on four different types of fibrous PLLA scaffold (aligned microfibers, aligned nanofibers, random microfibers, and random nanofibers) and on PLLA film (used as a reference). Substrate topography was found to influence the immune response activated by macrophages, especially in the early inflammation stage. Secretion of proinflammatory molecules by macrophage cells was chiefly dependent on fiber diameter. In particular, nanofibrous PLLA scaffolds minimized the inflammatory response when compared with films and microfibrous scaffolds. The histological evaluation demonstrated a higher number of foreign body giant cells on the PLLA film than on the micro- and nanofibrous scaffolds. In summary, our results indicate that the diameter of electrospun PLLA fibers, rather than fiber alignment, plays a relevant role in influencing in vitro macrophage activation and secretion of proinflammatory molecules.
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