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Editorial
. 2024 May 24;134(11):1448-1450.
doi: 10.1161/CIRCRESAHA.124.324572. Epub 2024 May 23.

gNR4Aly Link Bridging Cellular Metabolism, Lactylation, and Vascular Calcification

Rolando A Cuevas  1 , Parya Behzadi  1 , Cynthia St Hilaire  1   2
Affiliations
Editorial

gNR4Aly Link Bridging Cellular Metabolism, Lactylation, and Vascular Calcification

Rolando A Cuevas et al. Circ Res. .
No abstract available

Keywords: Editorials; elastic tissue; gene expression; insulin resistance; vascular calcification.

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Conflict of interest statement

Disclosures None.

Figures

Figure 1:
Figure 1:. NR4A3-dependent calcification in SMCs.
Metabolic changes induced by elevated circulating glucose or calcium and phosphate dysregulation, observed in diabetes and CKD, respectively, lead to the early transcriptional activity of NR4A3. This protein binds the promoter regions of ALDOA and PFKL, crucial glycolytic pathway genes. ALDOA- and PFKL-dependent hyperactivity of the glycolytic pathway leads to elevated pyruvate levels. Pyruvate is then converted to acetyl-CoA, succinyl-CoA, or lactyl-CoA, all molecules involved in acyl post-transcriptional modifications. LDH is a bidirectional enzyme that converts pyruvate to lactate. Lactate is metabolized into lactic-CoA by an unknown enzyme and transported into the nucleus, where the writer p300 catalyzes the condensation of the lactyl group to lysine 18 of histone 3, rendering H3K18la. Lactylated histone 3 at the Phospho1 gene locus increases its expression and promotes calcification in the vessel wall. Dotted arrows depict unknown mechanisms. ALDOA: aldolase A; CKD: chronic kidney disease; H3: histone 3; HS-CoA: Co-enzyme A.; lysine; La; lactylation. LDH; lactate dehydrogenase; PFKL: 6-phosphofructokinase TCA; tricarboxylic acid/citric acid cycle. Figure produced using BioRender.
See this image and copyright information in PMC

Comment on

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