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Pyruvate kinase M2 and Serine Dehydratase are Upregulated in the Macrophages of Human Aortic Atherosclerotic Lesions via Inflammatory Stimuli

Year: 2026

Type: article

Abstract: AIM: An altered vascular metabolism is closely linked to the cellular function in atherosclerotic lesions. The plasma pyruvate levels have been associated with aortic aneurysm progression in clinical studies. Pyruvate kinase M2 (PKM2) and serine dehydratase (SDS) catalyze the final steps of pyruvate production. While PKM2's role has been examined in experimental atherosclerosis or aneurysms, the involvement of SDS in atherosclerosis and the expression of PKM2 and SDS in human aortic lesions remain unknown. METHODS: Human aortic samples from vascular surgery were classified as early (n = 10), advanced (n = 9), or aneurysmal (n = 15) lesions. PKM2 and SDS expression were analyzed using immunohistochemistry. RESULTS: Immunopositive areas for these enzymes were larger in advanced and aneurysmal lesions than in early lesions and were predominantly expressed in macrophages. PKM2 was also detected in some smooth muscle cells and lymphocytes. In cultured human monocyte-derived macrophages, stimulation with tumor necrosis factor-α and interferon-γ increased the PKM2 and SDS expression levels. PKM2 silencing enhanced monocyte chemoattractant protein-1, interleukin-6, and SDS expression, and reduced transforming growth factor-β expression. SDS silencing significantly reduced the reactive oxygen species levels. CONCLUSIONS: The PKM2 and SDS expression levels increase in advanced human aortic atherosclerotic lesions and they are predominantly expressed in macrophages. The inflammatory microenvironment in atherosclerotic lesions upregulates the PKM2 and SDS expression in human macrophages. PKM2 may act as a negative regulator of vascular inflammation, and SDS may affect oxidative stress in inflammatory-stimulated macrophages.

Source: Journal of Atherosclerosis and Thrombosis

DOI: 10.5551/jat.66119