3 years ago

Telomerase reverse transcriptase protects against Angiotensin II induced microvascular endothelial dysfunction.

Karima Ait-Aissa, David D Gutterman, Andreas M Beyer, Joseph Hockenberry, Andrew O Kadlec
A rise in reactive oxygen species (ROS) may contribute to cardiovascular disease by reducing nitric oxide (NO) levels, leading to loss of NO's vasodilator and anti-inflammatory effects. Although primarily studied in the larger conduit arteries, excess ROS release and a corresponding loss of NO also occurs in the smaller resistance arteries of the microcirculation, but underlying mechanisms and therapeutic targets have not been fully characterized. We examined whether either of the two subunits of telomerase, telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC), affect microvascular ROS production and peak vasodilation at baseline and in response to in vivo administration to angiotensin II (ANG II). We report that genetic loss of TERT [max dilation (%): Vehicle 52.0{plus minus}6.1, L-NAME: 60.4{plus minus}12.9, Peg-CAT: 32.2{plus minus}12.2*; N = 9-19; *P<0.05] but not TERC [max dilation (%): Vehicle 79{plus minus}5; L-NAME 10.7{plus minus}9.8*; Peg-CAT 86.4{plus minus}8.4; N = 4-7; *P<0.05] promotes flow-induced ROS formation. Moreover, TERT KO exacerbates the microvascular dysfunction resulting from in vivo ANG II treatment, whereas TERT overexpression is protective [max dilation (%): vehicle: 88.22{plus minus}4.6 vs. ANG II (1000ng/kg/min) 74.0{plus minus}7.3; N = 4; P=NS]. Therefore, loss of TERT but not TERC may be a key contributor to the elevated microvascular ROS levels and reduced peak dilation observed in several cardiovascular disease pathologies.

Publisher URL: http://doi.org/10.1152/ajpheart.00472.2017

DOI: 10.1152/ajpheart.00472.2017

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