Therapeutic Potential of Annexin A1 in Ischemia Reperfusion Injury

Abstract

Cardiovascular disease (CVD) continues to be the leading cause of death in the world. Increased inflammation and an enhanced thrombotic milieu represent two major complications of CVD, which can culminate into an ischemic event. Treatment for these life-threatening complications remains reperfusion and restoration of blood flow. However, reperfusion strategies may result in ischemia–reperfusion injury (I/RI) secondary to various cardiovascular pathologies, including myocardial infarction and stroke, by furthering the inflammatory and thrombotic responses and delivering inflammatory mediators to the affected tissue. Annexin A1 (AnxA1) and its mimetic peptides are endogenous anti-inflammatory and pro-resolving mediators, known to have significant effects in resolving inflammation in a variety of disease models. Mounting evidence suggests that AnxA1, which interacts with the formyl peptide receptor (FPR) family, may have a significant role in mitigating I/RI associated complications. In this review article, we focus on how AnxA1 plays a protective role in the I/R based vascular pathologies.

Ischemia-Reperfusion Injury in Sickle Cell Disease

“…41 Annexin A1 is known to be protective in I/RI-based vascular inflammation and may have a role in the management of SCD. 42…”

Enhancing the Bystander and Abscopal Effects to Improve Radiotherapy Outcomes

“…There is mounting evidence that ANXA1, and its mimetic peptides (135), may have a major function in mitigating ischemia-reperfusion injury-associated complications (136). Moreover, chronic inflammation in tumors is frequent and promotes tumor growth, progression, and metastatic spreading, as well as treatment resistance (137).…”

“…In this process, ANXA1 is involved as a pre-resolving mediator (145). ANXA1 is a glucocorticoid-induced protein that is well-known to reproduce numerous anti-inflammatory effects of glucocorticoids and is implicated in the modulation of T-cell function and the adaptive immune response related to rheumatoid arthritis (146) and increasing data suggest that ANXA1, which act together with the formyl peptide receptor family, might have a major role in alleviating ischemia-reperfusion injury (136). ANXA1 interacts with p53 to co-regulate Bid expression and stimulate cell death after OGD/R via the caspase-3 pathway (147) and it has been described that ANXA1 is one of the molecules that is involved in p53-mediated radio-response and the abnormal expression of ANXA1 in nasopharyngeal carcinoma NPC might affect the apoptosis of tumor cells caused by ionizing radiation decreasing radiotherapeutic efficacy (148).…”

Use of DAMPs and SAMPs as Therapeutic Targets or Therapeutics: A Note of Caution

“…Moreover, the pathogenetic involvement of these molecules qualifies them as relevant drug targets or therapeutics as well. Indeed, accumulating preclinical data have encouraged envisaging DAMPs as therapeutic targets for inhibition [5,[12][13][14][15][16][17] and administration of SAMPs as candidate drugs [5,[18][19][20][21][22][23][24][25][26][27] for treating acute or chronic inflammatory disorders. On the other hand, DAMPs may also be…”