Targeting Hypoxia Signaling for Perioperative Organ Injury

Abstract

Perioperative organ injury has a significant impact on surgical outcomes and presents a leading cause of death in the United States. Recent research has pointed out an important role of hypoxia signaling in the protection from organ injury, including for example myocardial infarction, acute respiratory distress syndrome, acute kidney, or gut injury. Hypoxia induces the stabilization of hypoxia-inducible factors (HIFs), thereby leading to the induction of HIF target genes, which facilitates adaptive responses to low oxygen. In this review, we focus on current therapeutic strategies targeting hypoxia signaling in various organ injury models and emphasize potential clinical approaches to integrate these findings into the care of surgical patients. Conceptually, there are 2 options to target the HIF pathway for organ protection. First, drugs became recently available that promote the stabilization of HIFs, most prominently via inhibition of prolyl hydroxylase. These compounds are currently trialed in patients, for example, for anemia treatment or prevention of ischemia and reperfusion injury. Second, HIF target genes (such as adenosine receptors) could be activated directly. We hope that some of these approaches may lead to novel pharmacologic strategies to prevent or treat organ injury in surgical patients.

MicroRNA miR-223 as regulator of innate immunity

“…miRNAs are involved in almost all aspects of biological processes involving development, cellular differentiation, immune modulation, and pathogenic conditions. miRNAs alter mRNA function via blockade of translation or RNA degradation and it is predicted that approximately 60% of human genes are controlled by miRNAs . The specificity of mRNA targeting relies on a sequence of the miRNA, termed the ‘seed’ sequence, that binds complementary to the 3′ untranslated region (3′UTR) of the mRNA .…”

“…miRNAs alter mRNA function via blockade of translation or RNA degradation and it is predicted that approximately 60% of human genes are controlled by miRNAs. [1][2][3][4][5][6][7] The specificity of mRNA targeting relies on a sequence of the miRNA, termed the 'seed' sequence, that binds complementary to the 3 ′ untranslated region (3 ′ UTR) of the mRNA. 8 Thus one miRNA is capable Abbreviations: 3 ′ UTR, 3 ′ untranslated region; ALI, acute lung injury; ARDS, acute respiratory distress syndrome; BALF, bronchial alveolar lavage fluid; BM, bone marrow; DAMP, damage-associated molecular patterns; DC, dendritic cell; DGCR8, DiGeorge syndrome chromosomal region 8; DSS, dextran sodium sulfate; IBD, inflammatory bowel disease;…”

Mouth breathing impairs the development of temporomandibular joint at a very early stage

“…Nasal obstruction and hypoxia are both stimuli for the growth and development of rats throughout the process. Moreover, prolonged hypoxia can cause significant pathological changes in organs such as the skull, eyes, kidney, cardiovascular system, and gastrointestinal tract (Damman, Bloks, & Daha, 2015; Jakus, Jakus, Aračić, Stipić, & Vilović, 2017; Kim, Fong, Pilowsky, & Abbott, 2018; Klemm, Hurst, & Dias Blak, 2019; Wang et al., 2013; Yuan et al., 2018). However, at the very early stage, hypoxia is not as significant in remodeling the condyles of rats as mouth breathing.…”

The usefulness of perioperative lactate blood levels in patients undergoing heart valve surgery

“…The pathophysiological basis for postoperative MODS is cellular damage, which is manifested when cellular repair does not occur. During operations the oxygen consumption is inadequate to meet intraoperative metabolic requirements [1,2,9,10]. Hypoxia may result from insufficient blood supply caused by decreased cardiac output, reduced hemoglobin levels, or impaired absorption of oxygen by target cells.…”