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Decreased Telomerase Activity Sensitizes the Resistance Vasculature to Stress‐Induced Endothelial Dysfunction
Author(s) -
Beyer Andreas M.,
Hockenberry Joseph C.,
Hockenberry David C.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.678.1
Subject(s) - telomerase , reactive oxygen species , telomere , endothelial dysfunction , catalase , mitochondrial ros , oxidative stress , chemistry , mesenteric arteries , endothelium , endocrinology , vasodilation , medicine , microbiology and biotechnology , biology , biochemistry , dna , artery , gene
Telomerase, an established modulator of senescence and tissue aging is traditionally described as a nuclear enzyme crucial in telomere maintenance. Recently, telomerase has been shown to co‐localize with mitochondria and to be a novel regulator of mitochondrial derived reactive oxygen species (mtROS). Previous data show that decreased that telomerase activity (TA) increases mtROS production in human and mouse resistance vessels. We hypothesized that TA has an endothelial protective role under conditions of external stress. Mouse mesenteric arteries (~200 μm) were isolated and incubated in endothelial growth medium with a subconstrictor dose of angiotensin II (A II; 10 nM) or vehicle (V) with and without telomerase inhibitor BIRB 1532 (BIRB; 10 μm) for 15–20 h. Flow‐mediated dilation (FMD) was studied in vitro (pressure gradient 0–100 cm H 2 O). Values expressed as % Max dilation at 50 cmH 2 O ± SEM; * p < 0.05 vs. control one way ANOVA RM. A II caused a trend toward a decrease in FMD (V 57.0 ±9.2 vs. A II 42.8±13.6; n≥4). BIRB did not decrease FMD, but changed the mediator from NO to mtROS (catalase and rotenone inhibitable 1.5*±6.8; 11.9*±11.1). Co‐incubation with A II significantly reduced FMD (BIRB 59.1±10.6 vs. + A II 16.3*±7.4 n≥4). These data indicate that telomerase protects the microvascular endothelium from mtROS‐induced vascular dysfunction under stress.