Adaptive response to hypoxia and remote ischaemia pre‐conditioning: a new hypoxia‐inducible factors era in clinical medicine

Abstract

Transient ischaemia leads to tolerance to subsequent protracted ischaemia. This 'ischaemia pre-conditioning' results from the induction of numerous protective genes, involved in cell metabolism, proliferation and survival, in antioxidant capacity, angiogenesis, vascular tone and erythropoiesis. Hypoxia-inducible factors (HIF) play a pivotal role in this transcriptional adaptive response. HIF prolyl hydroxylases (PHDs), serving as oxygen sensors, control HIFα degradation. HIF-mediated ischaemic pre-conditioning can be achieved with the administration of PHD inhibitors, with the attenuation of organ injury under various hypoxic and toxic insults. Clinical trials are currently under way, evaluating PHD inhibitors as inducers of erythropoietin. Once their safety is established, their potential use might be further tested in clinical trials in various forms of acute ischaemic and toxic organ damage. Repeated transient limb ischaemia was also found to attenuate ischaemic injury in remote organs. This 'remote ischaemic pre-conditioning' phenomenon (RIP) has been extensively studied recently in small clinical trials, preceding, or in parallel with an abrupt insult, such as myocardial infarction, cardiac surgery or radiocontrast administration. Initial results are promising, suggesting organ protection. Large-scale multi-centre studies are currently under way, evaluating the protective potential of RIP in cardiac surgery, in the management of myocardial infarction and in organ transplantation. The mechanisms of organ protection provided by RIP are poorly understood, but HIF seemingly play a role as well. Thus, Inhibition of HIF degradation with PHD inhibitors, as well as RIP (in part through HIF), might develop into novel clinical interventions in organ protection in the near future.

The Acoustic Sensorimotor Gating Predicts the Efficiency of Hypoxic Preconditioning. Participation of the Cholinergic System in This Phenomenon

“…Hypoxic and ischaemic preconditioning, in which hypoxia is the main adaptive factor, mobilise the body's protection and thereby prevent or reduce the pathogenesis of severe hypoxia or ischaemic stroke in organs and tissues [1][2][3][4]. Moderate one-off hypobaric hypoxia (HBH; 11% O 2 for 60 min) provokes preconditioning and increases the resistance to severe hypobaric hypoxia (SHBH; 4.5% O 2 ).…”

Remote ischaemic conditioning in the context of type 2 diabetes and neuropathy: the case for repeat application as a novel therapy for lower extremity ulceration

“…Despite RIC and RRIC being reported as very safe and well tolerated in virtually all studies to date [87], a concern of ours, shared by Heyman et al is the potential for worsening or increased risk of proliferative diabetic retinopathy [214]. Diabetic foot ulcers occur particularly in patients with longstanding and/or poorly controlled diabetes, which are in turn both highly significant risk factors for diabetic retinopathy [215].…”

The role of hypoxia-induced factor in the regulation of oxygen homeostasis during reparative regeneration in compromised microcirculation

“…Последними исследованиями доказано, что гипоксические условия и нарушения клеточных ответов на гипоксию становятся существенными патогенетическими факторами задержки зажив-ления диабетических язв [28]. Нарушение зажив-ления ран при сахарном диабете характеризуется снижением ангиогенеза, уменьшением пролифе-рации и миграции фибробластов и кератиноцитов [29][30][31].…”

“…Сущность этого феномена заключается в кратковременном неповреждающем воздействии гипоксии на орга-ны или ткани, которое не приводит к структур-но-функциональным нарушениям, но вызывает адаптацию органов или тканей к последующим более тяжелым повреждающим воздействиям [37]. Как показано исследованиями последних лет, в механизмы гипоксического прекондициониро-вания вовлечен HIF-1α [31].…”