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HELLP Syndrome: Altered Hypoxic Response of the Fatty Acid Oxidation Regulator SIRT 4

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Abstract

The hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is frequently observed in mothers whose offspring have long-chain fatty acid oxidation defects. We previously found that fatty acid oxidation is compromised not only in these inborn errors of metabolism but also in human umbilical vein endothelial cells (HUVECs) from all pregnancies complicated by the HELLP syndrome. Sirtuins are oxidized nicotinamide adenine dinucleotide (NAD+)dependent deacetylases linked to the metabolic status of the cell. SIRT 4 is known to have regulatory functions in fatty acid oxidation. The HELLP syndrome is often associated with short-term hypoxia. We studied sirtuins (SIRT 1, SIRT 3, and SIRT 4) in HUVECs from pregnancies complicated by the HELLP syndrome and uncomplicated pregnancies exposed to hypoxia (n = 7 controls, 7 HELLP; 0, 10, 60, or 120 minutes of 2% O2). Protein levels of SIRT 4 were significantly higher in HUVECs from HELLP compared to control after 60 and 120 minutes of hypoxia. The NAD+ levels increased in a time-dependent manner.

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Authors and Affiliations

  1. Department of Paediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Mareike Sandvoß, Arne Björn Potthast MSc & Anibh Martin Das MD, PhD

  2. Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany

    Frauke von Versen-Höynck MD, PhD, MSc

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  1. Mareike Sandvoß
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  2. Arne Björn Potthast MSc
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  3. Frauke von Versen-Höynck MD, PhD, MSc
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  4. Anibh Martin Das MD, PhD
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Correspondence to Anibh Martin Das MD, PhD.

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Sandvoß, M., Potthast, A.B., von Versen-Höynck, F. et al. HELLP Syndrome: Altered Hypoxic Response of the Fatty Acid Oxidation Regulator SIRT 4. Reprod. Sci. 24, 568–574 (2017). https://doi.org/10.1177/1933719116667216

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