Therapeutic potential of the annexin A family in atherosclerosis

Abstract

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality and morbidity worldwide despite advancements in therapeutic options for the management of atherosclerosis (AS). Treatments that lower low-density lipoprotein (LDL) cholesterol levels, such as statins or proprotein convertase subtilisin/kexin type 9 inhibitors, have effectively reduced ASCVD risk. However, residual CVD risk remains high, highlighting the need for additional effective therapies. Recently, colchicine has been approved for managing AS, introducing new avenues for targeting inflammation, a key process in AS.

Various factors contribute to AS progression, such as endothelial dysfunction, leukocyte transmigration, vascular smooth muscle cell migration and phenotype-switching, increased lipid retention, production of pro-inflammatory cytokines and regulated cell death processes such as apoptosis. The annexin A (AnxA) family of proteins is well-known for their ability to bind Ca²⁺ and phospholipids, and they play diverse roles in inflammation, cell proliferation, migration, differentiation and signalling. Several AnxA proteins have been implicated in essential processes involved in AS development, including endothelial dysfunction, leukocyte transmigration and apoptosis.

In this mini-review, we highlight the roles of AnxA1, AnxA2, AnxA5, AnxA6, AnxA7 and AnxA8 in AS development and progression and their therapeutic potential in AS management.

Keywords

apoptosis / cardiovascular disease / endothelial cells / inflammation / macrophages / smooth muscle cells

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