Peroxisome Proliferator-Activated Receptors in Atherosclerosis and Metabolic Regulation

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that orchestrate lipid handling, glucose homeostasis and inflammatory responses across diverse cell types. In the context of atherosclerosis, PPARα, PPARγ and PPARδ influence cholesterol efflux, macrophage phenotype and plaque stability by regulating genes involved in fatty-acid transport, lipid uptake and oxidative metabolism. Activation of PPARα promotes β-oxidation pathways in hepatocytes and macrophages, limiting lipid accumulation in lesions, while PPARγ drives anti-inflammatory programmes and alternative macrophage activation, facilitating efferocytosis and resolution of inflammation. PPARδ contributes to vascular homeostasis through modulation of endothelial function and smooth muscle cell proliferation. Beyond plaque biology, PPARs integrate systemic energy balance, modulating insulin sensitivity and adipose tissue function. Synthetic agonists of PPARα and PPARγ have demonstrated metabolic benefits but their cardiovascular applications are tempered by adverse effects and complex tissue-specific roles. Current research seeks to delineate receptor isoform selectivity, novel endogenous ligands and cell-type-specific actions to refine therapeutic targeting of PPARs in cardiometabolic disease.

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Peroxisome Proliferator-Activated Receptors in Atherosclerosis and Metabolic Regulation publication trend

The graph below shows the total number of articles in peroxisome proliferator-activated receptors in atherosclerosis and metabolic regulation across all publications each year (not limited to Nature Index journals).

Technical terms

Peroxisome proliferator-activated receptors (PPARs): Nuclear receptor proteins that regulate gene expression in lipid metabolism, glucose homeostasis and inflammation.

Atherosclerosis: Chronic disease of arterial walls characterised by the accumulation of lipids, inflammatory cells and fibrous elements, forming plaques.

Macrophage polarization: Process by which macrophages adopt distinct functional states (pro-inflammatory M1 or anti-inflammatory M2) in response to microenvironmental signals.

Foam cell: Lipid-laden macrophage that arises from excessive uptake of modified lipoproteins and contributes to plaque development.

Efferocytosis: Phagocytic clearance of apoptotic cells by macrophages, essential for inflammation resolution and tissue homeostasis.

References

1. Myeloid cell ACE shapes cellular metabolism and function in PCSK-9 induced atherosclerosis. Frontiers in Immunology (2023).
2. STAT6 Signaling Mediates PPARγ Activation and Resolution of Acute Sterile Inflammation in Mice. Cells (2021).
3. PAK1 Silencing Attenuated Proinflammatory Macrophage Activation and Foam Cell Formation by Increasing PPARγ Expression. Oxidative Medicine and Cellular Longevity (2021).
4. PPARγ and the Innate Immune System Mediate the Resolution of Inflammation. PPAR Research (2015).