Therapeutic Potential of Annexin A1 Modulation in Kidney and Cardiovascular Disorders

Abstract

Renal and cardiovascular disorders are very prevalent and associated with significant morbidity and mortality. Among diverse pathogenic mechanisms, the dysregulation of immune and inflammatory responses plays an essential role in such disorders. Consequently, the discovery of Annexin A1, as a glucocorticoid-inducible anti-inflammatory protein, has fueled investigation of its role in renal and cardiovascular pathologies. Indeed, with respect to the kidney, its role has been examined in diverse renal pathologies, including acute kidney injury, diabetic nephropathy, immune-mediated nephropathy, drug-induced kidney injury, kidney stone formation, and renal cancer. Regarding the cardiovascular system, major areas of investigation include the role of Annexin A1 in vascular abnormalities, atherosclerosis, and myocardial infarction. Thus, this review briefly describes major structural and functional features of Annexin A1 followed by a review of its role in pathologies of the kidney and the cardiovascular system, as well as the therapeutic potential of its modulation for such disorders.

ANXA1sp attenuates sepsis‐induced myocardial injury by promoting mitochondrial biosynthesis and inhibiting oxidative stress and autophagy via SIRT3 upregulation

“…According to previous studies, the effects of peptides derived from the N-terminal region of ANXA1 are believed to be mediated via binding to formyl peptide receptors on the cell surface. 37 Therefore, ANXA1sp might also regulate SIRT3 expression in HL-1 cells via binding to formyl peptide receptors on the cell surface. However, the specific mechanisms remain to be further investigated in future studies.…”

Loss of Endothelial Annexin A1 Aggravates Inflammation‐Induched Vascular Aging

“…ANXA1 can reduce leukocyte adhesion to endothelial cells and have microvascular‐protective effects in the context of metabolic syndrome. [ 15 ] Collectively, this evidence suggests that ANXA1 might have therapeutic potential in cardiovascular disorders. Moreover, the impact of ANXA1 in other age‐related diseases, such as neurodegenerative diseases [ 16 ] and diabetes mellitus, [ 17 ] indicates that ANXA1 might affect the aging process.…”

Annexin A1 may contribute to the morphological changes in podocytes by mediating endocytic vesicle fusion and transport via promotion of SNARE assembly in idiopathic membranous nephropathy

“…Annexin A1 (ANXA1) is a Ca 2+ -binding protein that is expressed in a variety of tissues and immune cells. 7 The cellular sites of ANXA1 expression are the nucleus, cytoplasm, and cell membrane, in which ANXA1 performs multifaceted functions, such as functions in proliferation, apoptosis, survival, differentiation, migration, and anti-inflammatory processes. 8 Moreover, ANXA1 plays an important role in the innate immune response as an effector of glucocorticoid-mediated responses.…”