title: Low-Dose Fluvastatin and Valsartan Rejuvenate the Arterial Wall Through Telomerase Activity Increase in Middle-Aged Men.
abstract: OBJECTIVE
  Previously, we have shown that slightly to moderately aged arteries in middle-aged males can be rejuvenated functionally by sub-therapeutic, low-dose fluvastatin and valsartan treatment. Here, we explore whether this treatment could also increase telomerase activity. We hypothesized that telomerase activity might be associated with (1) an improvement of arterial wall properties and (2) a reduction of inflammatory/oxidative stress parameters (both observed in our previous studies).
  
  
  METHODS
  The stored blood samples from 130 apparently healthy middle-aged males treated with fluvastatin (10 mg daily), valsartan (20 mg daily), fluvastatin and valsartan combination (10 and 20 mg), respectively, and placebo (control), were analyzed. The samples were taken before and after treatment lasting 30 days, and 5 months after treatment discontinuation. Telomerase activity was measured in blood leukocytes by a TaqMan Gene Expression Assay.
  
  
  RESULTS
  Low-dose fluvastatin or valsartan increased telomerase activity (106.9% and 59.5% respectively; both p < 0.05, vs. control), whereas their combination was even more effective (an increase of 228.0%; p < 0.001, vs. control). No change was noted in the control group. Importantly, increased telomerase activity obtained in the combination group significantly correlated with arterial function, measured by flow-mediated dilation (FMD) (r = 0.79; p < 0.001) and C-reactive protein concentration (r = -0.54; p = 0.02) and total anti-oxidative status (r = 0.50; p = 0.03).
  
  
  CONCLUSIONS
  We found that a low-dose combination of fluvastatin and valsartan substantially increased telomerase activity, which significantly correlated with an improvement of endothelial function and a decrease of inflammation/oxidative stress. These findings could lead to a new innovative approach to arterial rejuvenation.
authors.affiliation: 1 Department of Vascular Diseases, Ljubljana University Medical Centre , Ljubljana, Slovenia .
authors.forename: Miodrag
authors.initials: M
authors.lastname: Janić
authors.affiliation: 1 Department of Vascular Diseases, Ljubljana University Medical Centre , Ljubljana, Slovenia .
authors.forename: Mojca
authors.initials: M
authors.lastname: Lunder
authors.affiliation: 2 Department of Molecular Diagnostics, Institute of Oncology Ljubljana , Ljubljana, Slovenia .
authors.forename: Petra
authors.initials: P
authors.lastname: Cerkovnik
authors.affiliation: 2 Department of Molecular Diagnostics, Institute of Oncology Ljubljana , Ljubljana, Slovenia .
authors.forename: Uršula
authors.initials: U
authors.lastname: Prosenc Zmrzljak
authors.affiliation: 2 Department of Molecular Diagnostics, Institute of Oncology Ljubljana , Ljubljana, Slovenia .
authors.forename: Srdjan
authors.initials: S
authors.lastname: Novaković
authors.affiliation: 1 Department of Vascular Diseases, Ljubljana University Medical Centre , Ljubljana, Slovenia .
authors.forename: Mišo
authors.initials: M
authors.lastname: Šabovič
mesh_terms: D001158:Arteries / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D000077340:Fluvastatin; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D012060:Rejuvenation / Q000502:physiology*; D019098:Telomerase / Q000378:metabolism*; D000068756:Valsartan / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D000077340:Fluvastatin; D000068756:Valsartan; D019098:Telomerase