Effects of Remote Ischemic Preconditioning on Heme Oxygenase-1 Expression and Cutaneous Wound Repair

Abstract

Skin wounds may lead to scar formation and impaired functionality. Remote ischemic preconditioning (RIPC) can induce the anti-inflammatory enzyme heme oxygenase-1 (HO-1) and protect against tissue injury. We aim to improve cutaneous wound repair by RIPC treatment via induction of HO-1. RIPC was applied to HO-1-luc transgenic mice and HO-1 promoter activity and mRNA expression in skin and several other organs were determined in real-time. In parallel, RIPC was applied directly or 24h prior to excisional wounding in mice to investigate the early and late protective effects of RIPC on cutaneous wound repair, respectively. HO-1 promoter activity was significantly induced on the dorsal side and locally in the kidneys following RIPC treatment. Next, we investigated the origin of this RIPC-induced HO-1 promoter activity and demonstrated increased mRNA in the ligated muscle, heart and kidneys, but not in the skin. RIPC did not change HO-1 mRNA and protein levels in the wound 7 days after cutaneous injury. Both early and late RIPC did not accelerate wound closure nor affect collagen deposition. RIPC induces HO-1 expression in several organs, but not the skin, and did not improve excisional wound repair, suggesting that the skin is insensitive to RIPC-mediated protection.

Ferritin Genes Overexpression in PBMC and a Rise in Exercise Performance as an Adaptive Response to Ischaemic Preconditioning in Young Men

“…Some pathogens and microvascular clotting, vasoconstriction, and molecules released in the context of tissue damage can influence lyses and concomitant Hb leakage into plasma [31]. Probably the upregulation of heme oxygenase described in several studies confirms heme degradation under RIPC conditions [4].…”

“…According to Kolh [3] the protective actions of IPC are dependent on the type of organ and applied ischemic preconditioning protocol. Regardless of that, the changes caused by ischaemia start at the molecular level: it changes the activation of some genes, post-transcriptional modification of mRNA, and protein activity in the cells [3, 4]. It has been shown that IPC induces changes in genes expression.…”

“…It has been shown that IPC induces changes in genes expression. The changes in mRNA levels most commonly refer to genes associated with inflammation [4, 5], activation of NF- κ B acute-phase response signaling [6], and energy metabolism [7]. In addition, a study on human subjects demonstrated that IPC downregulates leukocyte inflammatory gene expression and suppresses circulating neutrophils activation [8].…”

“…In the current literature there is some data which indicates that an increase in ferritin level in cells plays a protective role against prolonged ischaemia [15, 16]. Effect on ischemia has been done on different types of cells (such like kidney, liver, lung, and skin cells) [4]; however we are not aware of any studies where the responses of ischemia have been evaluated on PBMC human cells. Furthermore, it is hard to establish how exactly IPC influences expression of genes encoding ferritin in humans.…”

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

“…An elegant approach to analyze HO-1 expression in different organs due to RIC was done by Cremers et al measuring HO-1 promotor activity and HO-1 mRNA in HO-1 luc transgenic mice [144]. These mice carry a transgene consisting of the full-length mouse HO-1 promotor fused to the reporter gene luciferase (luc).…”