Apoptosis Regulation in Inflammatory and Metabolic Disorders

Apoptosis—or programmed cell death—serves a pivotal role in maintaining tissue homeostasis by eliminating damaged or superfluous cells. In inflammatory and metabolic disorders, dysregulation of apoptosis contributes to chronic disease progression. Within inflamed sites, macrophages adopt distinct activation states, influencing apoptotic pathways in both immune and parenchymal cells. In metabolic tissues, notably adipose and hepatic tissue, apoptosis intersects with lipid metabolism and insulin signalling. An intricate network of cytokines, death receptors and intracellular mediators such as caspases and Bcl-2 family proteins orchestrates cell fate decisions. Aberrant inhibition of apoptosis in macrophages can amplify inflammatory cascades, whereas excessive apoptosis of parenchymal cells may precipitate fibrosis and organ dysfunction. Recent advances reveal the dualistic nature of modulators like CD5L, also known as apoptosis inhibitor of macrophage (AIM), which can both restrain macrophage death and promote clearance of apoptotic debris, restoring tissue integrity. Understanding the regulatory nodes that balance survival and cell death has global significance—from curbing atherosclerotic plaque formation and aneurysm progression to ameliorating obesity-associated inflammation, chronic kidney disease and non-alcoholic fatty liver disease. Therapeutic strategies targeting apoptosis pathways offer promise in mitigating inflammatory damage and metabolic derangements, underscoring the translational potential of this research frontier.

Research from Nature Portfolio

Recent studies have demonstrated that neutralising the apoptosis inhibitor of macrophage protein can attenuate vascular inflammation and aneurysm growth. In murine models, administration of a monoclonal antibody directed against AIM reduced inflammatory macrophage accumulation within the aortic wall, enhanced caspase-3 activity and preserved extracellular matrix integrity, thereby slowing aneurysm progression. Complementing this, mechanistic work on AIM processing has uncovered a proteolytic cleavage event in circulation that releases AIM from its immunoglobulin M carrier, permitting renal excretion. Cleaved AIM retains its capacity to facilitate phagocytic removal of cell debris in injured tissue, highlighting a physiological regulatory mechanism that limits chronic inflammation and suggests avenues for engineering safer AIM-based therapies.

Apoptosis Regulation in Inflammatory and Metabolic Disorders publication trend

The graph below shows the total number of articles in apoptosis regulation in inflammatory and metabolic disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Apoptosis: Programmed cell death regulated by caspases and characterised by cellular condensation and DNA fragmentation.

Macrophage: Innate immune cell capable of phagocytosis, cytokine secretion and modulation of inflammatory responses.

Caspase: Family of cysteine proteases that execute apoptosis by cleaving specific substrates.

Cytokine: Signalling protein produced by immune cells to regulate inflammation and cell survival.

Phagocytosis: Process by which cells engulf and degrade apoptotic bodies, pathogens or debris to maintain tissue health.

References

1. Administration of an antibody against apoptosis inhibitor of macrophage prevents aortic aneurysm progression in mice. Scientific Reports (2024).
2. A proteolytic modification of AIM promotes its renal excretion. Scientific Reports (2016).
3. The effects of apoptosis inhibitor of macrophage in kidney diseases. European Journal of Medical Research (2024).
4. Multifaceted Roles of CD5L in Infectious and Sterile Inflammation. International Journal of Molecular Sciences (2021).