The Role of Heme Oxygenase-1 in Remote Ischemic and Anesthetic Organ Conditioning

Abstract

The cytoprotective effects of the heme oxygenase (HO) pathway are widely acknowledged. These effects are mainly mediated by degradation of free, pro-oxidant heme and the generation of carbon monoxide (CO) and biliverdin. The underlying mechanisms of protection include anti-oxidant, anti-apoptotic, anti-inflammatory and vasodilatory properties. Upregulation of the inducible isoform HO-1 under stress conditions plays a crucial role in preventing or reducing cell damage. Therefore, modulation of the HO-1 system might provide an efficient strategy for organ protection. Pharmacological agents investigated in the context of organ conditioning include clinically used anesthetics and sedatives. A review from Hoetzel and Schmidt from 2010 nicely summarized the effects of anesthetics on HO-1 expression and their role in disease models. They concluded that HO-1 upregulation by anesthetics might prevent or at least reduce organ injury due to harmful stimuli. Due to its clinical safety, anesthetic conditioning might represent an attractive pharmacological tool for HO-1 modulation in patients. Remote ischemic conditioning (RIC), first described in 1993, represents a similar secure option to induce organ protection, especially in its non-invasive form. The efficacy of RIC has been intensively studied herein, including on patients. Studies on the role of RIC in influencing HO-1 expression to induce organ protection are emerging. In the first part of this review, recently published pre-clinical and clinical studies investigating the effects of anesthetics on HO-1 expression patterns, the underlying signaling pathways mediating modulation and its causative role in organ protection are summarized. The second part of this review sums up the effects of RIC.

Donor Preconditioning with Inhaled Sevoflurane Mitigates the Effects of Ischemia-Reperfusion Injury in a Swine Model of Lung Transplantation

“…It has been shown that anesthetic conditioning (AC) may attenuate the IRI process [ 11 , 12 ]. AC is safe and easy to perform and is routinely used for anesthesia in surgical patients [ 22 ].…”

“…Increasing evidence shows that the administration of volatile anesthetics may offer protection against organ ischemic damage through a mechanism called anesthetic conditioning (AC) and attenuate the IRI process [ 11 , 12 ]. Based on the timing of administration, AC is defined as preconditioning (before ischemia), perconditioning (during ischemia), or postconditioning (after reperfusion).…”

Heme Oxygenase-1-Mediated Autophagy Protects against Oxidative Damage in Rat Nucleus Pulposus-Derived Mesenchymal Stem Cells

“…Therefore, we then tried to reveal the self-adaptive protection mechanism, which might provide a novel target to reverse endogenous repair failure and promote the development of therapies for IVD degeneration. 9 Oxidative Medicine and Cellular Longevity HO-1, which has been identified in many pathophysiological scenarios, serves a critical biological function as the rate-limiting enzyme in the metabolism of heme to generate biliverdin, carbon monoxide, and iron [30,31]. As a cellular stress protein, HO-1 can function as one of the most important factors of cell adaptation to oxidative stress and exert cytoprotective effects against environment stress-induced inflammation and cell death [32].…”

Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients

“…Heme oxygenase-1 (HO-1), also known as a 32 kDa heat-shock protein, is an intracellular enzyme that catalyzes the degradation of heme into biliverdin, ferrous iron, and carbon monoxide (CO), with biliverdin being subsequently catabolized into bilirubin [7][8][9][10][11]. HO-1 is highly induced in response to various stress signals, such as free heme and hemoglobin, inflammatory cytokines, ischemia, endotoxins, irradiation, and mucosal damage [9][10][11][12][13][14][15][16].…”