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Cytokines and metabolic syndrome: The perfect storm for arterial aging

      The role of the aging process in favoring the onset of vascular disorders is very well known and it is now recognized as an independent risk factor for major cardiovascular events. The mechanisms causing the detrimental effect of aging on cardiovascular function are numerous, including the role of risk factors such as diabetes, oxidative stress, hypertension, gender smoking and others. In the last years several observations have pointed also to a role of inflammatory factors as accelerators of the senescence of vascular cells [
      • Kunieda T.
      • Minamino T.
      • Nishi J.
      • et al.
      Angiotensin II induces premature senescence of vascular smooth muscle cells and accelerates the development of atherosclerosis via a p21-dependent pathway.
      ]. While acute inflammation serves to resolve pathogen infection and stresses, which promote tissue repair, persistent inflammation results in maladaptive tissue remodeling and damage. It is noteworthy that while inflammatory factors are correlated to vascular aging in vivo in human subjects [
      • Lind L.
      • Siegbahn A.
      • Hulthe J.
      • Elmgren A.
      C-reactive protein and e-selectin levels are related to vasodilation in resistance, but not conductance arteries in the elderly: the prospective investigation of the Vasculature in Uppsala Seniors (PIVUS) study.
      ], experimental approaches that limited the activity of inflammatory factors such as TNF-alpha, Angiotensin II or RAGE often slowed vascular aging in vitro and in vivo [
      • Kunieda T.
      • Minamino T.
      • Nishi J.
      • et al.
      Angiotensin II induces premature senescence of vascular smooth muscle cells and accelerates the development of atherosclerosis via a p21-dependent pathway.
      ,
      • Csiszar A.
      • Labinskyy N.
      • Smith K.
      • Rivera A.
      • Orosz Z.
      • Ungvari Z.
      Vasculoprotective effects of anti-tumor necrosis factor-alpha treatment in aging.
      ,
      • Lin L.
      • Park S.
      • Lakatta E.G.
      RAGE signaling in inflammation and arterial aging.
      ]. Interestingly, Adiponectin, an hormone secreted by the adipose tissue that is negatively regulated by inflammatory factors, may represent a link between aging and the development of cardiovascular disorders [
      • Chang J.
      • Li Y.
      • Huang Y.
      • et al.
      Adiponectin prevents diabetic premature senescence of endothelial progenitor cells and promotes endothelial repair by suppressing the p38 MAP kinase/p16INK4A signaling pathway.
      ,
      • Windham B.G.
      • Griswold M.E.
      • Farasat S.M.
      • et al.
      Influence of leptin, adiponectin, and resistin on the association between abdominal adiposity and arterial stiffness.
      ,
      • Rizza S.
      • Gigli F.
      • Galli A.
      • et al.
      Adiponectin isoforms in elderly patients with or without coronary artery disease.
      ]. Clearly, because obesity and diabetes themselves increase cardiovascular risk, one could reason that the aging of the vascular system may be accelerated by the interaction between metabolic and inflammatory factors [

      Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. JAMA 2001;285:2486–97.

      ]. A limit to understand the nature of this interaction is due to the methods available to identify arterial aging in vivo. However measurements of arterial stiffness and aortic pulse waive velocity are generally considered affordable clinical surrogates for arterial aging [
      • Scuteri A.
      • Najjar S.S.
      • Muller D.C.
      • et al.
      Metabolic syndrome amplifies the age-associated increases in vascular thickness and stiffness.
      ].

      Keywords

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      References

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