Annexin-A1: Therapeutic potential in microvascular disease

Journal article

Annexin-A1 (ANXA1) was first discovered in the early 1980's as a protein, which mediates (some of the) anti-inflammatory effects of glucocorticoids. Subsequently, the role of ANXA1 in inflammation has been extensively studied. The biology of ANXA1 is complex and it has many different roles in both health and disease. Its effects as a potent endogenous anti-inflammatory mediator are well-described in both acute and chronic inflammation and its role in activating the pro-resolution phase receptor, FPR2, has been described and is now being exploited for therapeutic benefit. In the present mini review, we will endeavor to give an overview of ANXA1 biology in relation to inflammation and functions that mediate pro-resolution that are independent of glucocorticoid induction. We will focus on the role of ANXA1 in diseases with a large inflammatory component focusing on diabetes and microvascular disease. Finally, we will explore the possibility of exploiting ANXA1 as a novel therapeutic target in diabetes and the treatment of microvascular disease. Annexin-A1 (ANXA1) is a 37 kDa phospholipid-binding protein widely expressed in many tissues including leukocytes, lymphocytes, epithelial cells, and endothelial cells. ANXA1 is present intracellularly and at the membrane (1), but can also be secreted into the circulation were it can signal in both an autocrine and paracrine manner (2, 3). However, in disease ANXA1 levels are modulated most notably when endogenous glucocorticoids levels are altered. Patients with Addison's disease exhibit lower levels of ANXA1 in leukocytes due to reduced cortisol production. In contrast, patients with Cushing's syndrome have elevated levels of ANXA1 secondary to excessive cortisol production (4).

Authors: Purvis, G; Solito, E; Thiemermann, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Frontiers Media
• Journal: Frontiers in Immunology
• Volume: 10
• Article number: 938
• Publication date: 2019-04-30
• Acceptance date: 2019-04-11
• DOI: 10.3389/fimmu.2019.00938
• EISSN: 1664-3224
• Pmid: 31114582
• Language: English
• Keywords: Annexin-A1 (ANXA1); signaling; tissue protection; inflammation; diabetes