Dataset Information

Endothelial OCT4 is atheroprotective by preventing metabolic and phenotypic dysfunction.

ABSTRACT:

Aims

Until recently, the pluripotency factor Octamer (ATGCAAAT)-binding transcriptional factor 4 (OCT4) was believed to be dispensable in adult somatic cells. However, our recent studies provided clear evidence that OCT4 has a critical atheroprotective role in smooth muscle cells. Here, we asked if OCT4 might play a functional role in regulating endothelial cell (EC) phenotypic modulations in atherosclerosis.

Methods and results

Specifically, we show that EC-specific Oct4 knockout resulted in increased lipid, LGALS3+ cell accumulation, and altered plaque characteristics consistent with decreased plaque stability. A combination of single-cell RNA sequencing and EC-lineage-tracing studies revealed increased EC activation, endothelial-to-mesenchymal transitions, plaque neovascularization, and mitochondrial dysfunction in the absence of OCT4. Furthermore, we show that the adenosine triphosphate (ATP) transporter, ATP-binding cassette (ABC) transporter G2 (ABCG2), is a direct target of OCT4 in EC and establish for the first time that the OCT4/ABCG2 axis maintains EC metabolic homeostasis by regulating intracellular heme accumulation and related reactive oxygen species production, which, in turn, contributes to atherogenesis.

Conclusions

These results provide the first direct evidence that OCT4 has a protective metabolic function in EC and identifies vascular OCT4 and its signalling axis as a potential target for novel therapeutics.

SUBMITTER: Shin J

PROVIDER: S-EPMC9890633 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Endothelial OCT4 is atheroprotective by preventing metabolic and phenotypic dysfunction.

Shin Junchul J Tkachenko Svyatoslav S Chaklader Malay M Pletz Connor C Singh Kanwardeep K Bulut Gamze B GB Han Young Min YM Mitchell Kelly K Baylis Richard A RA Kuzmin Andrey A AA Hu Bo B Lathia Justin D JD Stenina-Adognravi Olga O Podrez Eugene E Byzova Tatiana V TV Owens Gary K GK Cherepanova Olga A OA

Cardiovascular research 20220801 11

<h4>Aims</h4>Until recently, the pluripotency factor Octamer (ATGCAAAT)-binding transcriptional factor 4 (OCT4) was believed to be dispensable in adult somatic cells. However, our recent studies provided clear evidence that OCT4 has a critical atheroprotective role in smooth muscle cells. Here, we asked if OCT4 might play a functional role in regulating endothelial cell (EC) phenotypic modulations in atherosclerosis.<h4>Methods and results</h4>Specifically, we show that EC-specific Oct4 knockout ...[more]

PMID: 35325071

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Dataset Information

Endothelial OCT4 is atheroprotective by preventing metabolic and phenotypic dysfunction.

Aims

Methods and results

Conclusions

Publications

Endothelial OCT4 is atheroprotective by preventing metabolic and phenotypic dysfunction.

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