TY - JOUR
TI - Antiapoptotic Effect of beta(1) Blockers in Ascending Thoracic Aortic
Smooth Muscle Cells: The Role of HSP70 Expression
AU - Rizos, Ioannis K.
AU - Tsoporis, James N.
AU - Toumpoulis, Ioannis K. and
AU - Salpeas, Vasileios
AU - Izhar, Shehla
AU - Rigopoulos, Angelos G. and
AU - Sakadakis, Eleftherios A.
AU - Parker, Thomas G.
JO - Journal of Cardiovascular Pharmacology
PY - 2018
VL - 72
TODO - 2
SP - 86-96
PB - Lippincott, Williams & Wilkins
SN - 0160-2446, 1533-4023
TODO - 10.1097/FJC.0000000000000596
TODO - beta(1 )blockers; apoptosis; heat shock proteins; aneurism; nitric oxide
TODO - Heat shock proteins (HSPs) play an important role in the cellular
adaptation to stress, a requisite for cell survival. The aortic wall
appears to be a target for increased expression of HSPs during surgical
stress. We aimed to define the expression and function of aortic HSP70
in 31 patients with normal ascending thoracic aortic diameter who
underwent aortic valve replacement due to aortic valve stenosis and in
35 patients with dilated ascending thoracic aorta who underwent
replacement of an ascending thoracic aortic aneurysm. To elucidate
responsible signaling mechanisms we used an in vitro model of rat
hypoxic aortic vascular smooth muscle cell (AVSMC) cultures. We
demonstrated an increase in AVSMC HSP70 and an attenuation of the
apoptotic markers (TUNEL-positive nuclei, caspase-3 activity, Bax/Bc12
ratio) in aortic wall tissue specimens from both aortic valve stenosis
and ascending thoracic aortic aneurysm patients on beta(1) blockade with
metoprolol. In vitro, metoprolol treatment of hypoxic rat AVSMCs
increased nitric oxide (NO) production, induced heat shock factor 1
transport to the nucleus, upregulated HSP70, decreased p53
phosphorylation and attenuated apoptosis. Blockade of NO production,
resulted in decreased HSP70 and prevented the metoprolol-induced
anti-apoptotic response of hypoxic AVSMCs. We demonstrate an
anti-apoptotic effect of metoprolol dependent on NO-induced HSP70
expression, and thus augmentation of HSP70 expression should be
considered as a therapeutic approach to limit apoptosis in the human
ascending thoracic aorta of patients undergoing cardiac surgery.
ER -