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Low-dose fluvastatin and valsartan rejuvenate the arterial wall through telomerase activity increase in the middle-aged men.
Janic M, Lunder M, Cerkovnik P, Prosenc Zmrzljak U, Novakovic S, Sabovic M
Abstract:
BACKGROUND AND AIM:
We have previously shown that slightly to moderately aged arteries in middle-aged males can be functionally rejuvenated by subtherapeutic, low-dose fluvastatin and valsartan treatment. Herein, we aim to explore whether this treatment could also increase telomerase activity. We hypothesized that telomerase activity might be associated with i) an improvement of arterial wall properties and ii) 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 analysed. The samples were taken before and after treatment lasting 30 days, and 5 months after treatment discontinuation. Telomerase activity was measured in blood leucocytes by TaqMan Gene Expression Assay.
RESULTS:
Low-dose fluvastatin or valsartan increased telomerase activity (106.9% and 59.5% (both P<0.05, vs. control), respectively), while 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 i) arterial function, measured by flow-mediated dilation (FMD) (r=0.79; P<0.001) and ii) C-reactive protein concentration (r=-0.54; P=0.02) and total antioxidative status (r=0.50; P=0.03).
CONCLUSION:
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.
We have previously shown that slightly to moderately aged arteries in middle-aged males can be functionally rejuvenated by subtherapeutic, low-dose fluvastatin and valsartan treatment. Herein, we aim to explore whether this treatment could also increase telomerase activity. We hypothesized that telomerase activity might be associated with i) an improvement of arterial wall properties and ii) 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 analysed. The samples were taken before and after treatment lasting 30 days, and 5 months after treatment discontinuation. Telomerase activity was measured in blood leucocytes by TaqMan Gene Expression Assay.
RESULTS:
Low-dose fluvastatin or valsartan increased telomerase activity (106.9% and 59.5% (both P<0.05, vs. control), respectively), while 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 i) arterial function, measured by flow-mediated dilation (FMD) (r=0.79; P<0.001) and ii) C-reactive protein concentration (r=-0.54; P=0.02) and total antioxidative status (r=0.50; P=0.03).
CONCLUSION:
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.
