Dataset Information

Atherogenic Lipoprotein(a) Increases Vascular Glycolysis, Thereby Facilitating Inflammation and Leukocyte Extravasation.

ABSTRACT:

Rationale

Patients with elevated levels of lipoprotein(a) [Lp(a)] are hallmarked by increased metabolic activity in the arterial wall on positron emission tomography/computed tomography, indicative of a proinflammatory state.

Objective

We hypothesized that Lp(a) induces endothelial cell inflammation by rewiring endothelial metabolism.

Methods and results

We evaluated the impact of Lp(a) on the endothelium and describe that Lp(a), through its oxidized phospholipid content, activates arterial endothelial cells, facilitating increased transendothelial migration of monocytes. Transcriptome analysis of Lp(a)-stimulated human arterial endothelial cells revealed upregulation of inflammatory pathways comprising monocyte adhesion and migration, coinciding with increased 6-phophofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)-3-mediated glycolysis. ICAM (intercellular adhesion molecule)-1 and PFKFB3 were also found to be upregulated in carotid plaques of patients with elevated levels of Lp(a). Inhibition of PFKFB3 abolished the inflammatory signature with concomitant attenuation of transendothelial migration.

Conclusions

Collectively, our findings show that Lp(a) activates the endothelium by enhancing PFKFB3-mediated glycolysis, leading to a proadhesive state, which can be reversed by inhibition of glycolysis. These findings pave the way for therapeutic agents targeting metabolism aimed at reducing inflammation in patients with cardiovascular disease.

SUBMITTER: Schnitzler JG

PROVIDER: S-EPMC7208285 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Atherogenic Lipoprotein(a) Increases Vascular Glycolysis, Thereby Facilitating Inflammation and Leukocyte Extravasation.

Schnitzler Johan G JG Hoogeveen Renate M RM Ali Lubna L Prange Koen H M KHM Waissi Farahnaz F van Weeghel Michel M Bachmann Julian C JC Versloot Miranda M Borrelli Matthew J MJ Yeang Calvin C De Kleijn Dominique P V DPV Houtkooper Riekelt H RH Koschinsky Marlys L ML de Winther Menno P J MPJ Groen Albert K AK Witztum Joseph L JL Tsimikas Sotirios S Stroes Erik S G ESG Kroon Jeffrey J

Circulation research 20200312 10

<h4>Rationale</h4>Patients with elevated levels of lipoprotein(a) [Lp(a)] are hallmarked by increased metabolic activity in the arterial wall on positron emission tomography/computed tomography, indicative of a proinflammatory state.<h4>Objective</h4>We hypothesized that Lp(a) induces endothelial cell inflammation by rewiring endothelial metabolism.<h4>Methods and results</h4>We evaluated the impact of Lp(a) on the endothelium and describe that Lp(a), through its oxidized phospholipid content, a ...[more]

PMID: 32160811

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Dataset Information

Atherogenic Lipoprotein(a) Increases Vascular Glycolysis, Thereby Facilitating Inflammation and Leukocyte Extravasation.

Rationale

Objective

Methods and results

Conclusions

Publications

Atherogenic Lipoprotein(a) Increases Vascular Glycolysis, Thereby Facilitating Inflammation and Leukocyte Extravasation.

Similar Datasets

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