The role and mechanism of the annexin A1 peptide Ac2‐26 in rats with cardiopulmonary bypass lung injury

Abstract

The main causes of lung injury after cardiopulmonary bypass (CPB) are systemic inflammatory response syndrome (SIRS) and pulmonary ischaemia‐reperfusion injury (IR‐I). SIRS and IR‐I are often initiated by a systemic inflammatory response. The present study investigated whether the annexin A1 (ANX‐A1) peptidomimetic Ac2‐26 by binding to formyl peptide receptors (FPRs) inhibit inflammatory cytokines and reduce lung injury after CPB. Male rats were randomized to the following five groups (n = 6, each): sham, exposed to pulmonary ischaemic‐reperfusion (IR‐I), IR‐I plus Ac2‐26, IR‐I plus the FPR antagonist, BoC2 (N‐tert‐butyloxycarbonyl‐Phe‐Leu‐Phe‐Leu‐Phe) and IR‐I plus Ac2‐26 and BoC2. Treatment with Ac2‐26 improved the oxygenation index, an effect blocked by BoC2. Histopathological analysis of the lung tissue revealed that the degree of lung injury was significantly less (P < 0.05) in the Ac2‐26‐treated rats compared to the other experimental groups exposed to IR‐I. Ac2‐26 treatment reduced the levels of the inflammatory cytokines TNF‐α, IL‐1β, ICAM‐1 and NF‐κB‐p65 (P < 0.05) compared to the vehicle‐treated group exposed to IR‐I. In conclusion, the annexin A1 (ANX‐A1) peptidomimetic Ac2‐26 by binding to formyl peptide receptors inhibit inflammatory cytokines and reduce ischaemic‐reperfusion lung injury after cardiopulmonary bypass.

The role of annexin A1 peptide in regulating PI3K/Akt signaling pathway to reduce lung injury after cardiopulmonary bypass in rats

“…This experimental model establishes a model of extracorporeal circulation IR injury using the protocol of He et al [16] . Rat anesthesia was injected intraperitoneally with 1% sodium pentobarbital 50 mg•kg -1 .…”

“…3.5 Expression of PI3K, p-PI3K, Akt, p-Akt (Ser473), NF-κB(p65), p-NF-κB(p65), and AnxA1 in rat lung tissue Detect the expression of p-PI3K and PI3K in the lung tissues in each group.PI3K was set as an internal reference, and the ratio of p-PI3K/PI3K was calculated to re ect the expression level of p-PI3K [16,17] . At the end of the experiment, the expression of PI3K in the lung tissues of rats in the IR, D, A, and AL groups was upregulated (P<0.05).…”

“…This experimental model established a model of extracorporeal circulation I/R injury using the protocol described by He et al 11 A detailed description of the experimental model is added in detail in the Supplemental Material.…”

Narrative review of the systemic inflammatory reaction to cardiac surgery and cardiopulmonary bypass

“…47 Aside of the IL-10 protective effect (i.e., I-kB phosphorylation suppression/inhibition of NF-kB-DNA coupling 40 ), repression of NF-kB activity and consequent amelioration of IRI were obtained by annexin A1 (ANX-A1; i.e., endogenous anti-inflammatory protein associated with I-kB kinases binding to Heat Shock Protein Family B Member 1) peptidomimetic Ac2-26 in CPB animal models. 48 NF-kB activation occurs also throughout the RANKL-RANK interaction: the receptor activator of the NF-kB ligand (RANKL), its membrane receptor RANK and its decoy receptor osteo-protegrin (OPG) have been described as involved in inflammatory diseases. 49 Interestingly, evidence of OPG/RANKL/RANK activation following either on-pump or off-pump CABG was reported: augmented expression of NF-kB p50 subunit in T-cells was associated to increased postoperative OPG levels.…”

ANNEXIN A1: Roles in Placenta, Cell Survival, and Nucleus

“…The protective anti-inflammatory action of ANXA1 has since been demonstrated in several models, including arthritis, heterologous skin transplantation, cancer, eye allergy, heart failure, lung injury, nonalcoholic steatosis, myocardial infarction, and skeletal muscle injury [19][20][21][22][23][24][25][26][27][28][29][30].…”