Platelets in preeclamptic pregnancies fail to exhibit the decrease in mitochondrial oxygen consumption rate seen in normal pregnancies

Abstract

Cellular oxygen consumption and lactate production rates have been measured in both placental and myometrial cells to study obstetrics-related disease states such as preeclampsia. Platelet metabolic alterations indicate systemic bioenergetic changes that can be useful as disease biomarkers. We tested the hypothesis that platelet mitochondria display functional alterations in preeclampsia. Platelets were harvested from women in the third trimester of either a healthy, non-preeclamptic or preeclamptic pregnancy, and from healthy, non-pregnant women. Using Seahorse respirometry, we analyzed platelets for oxygen consumption (OCR) and extracellular acidification (ECAR) rates, indicators of mitochondrial electron transport and glucose metabolism, respectively. There was a 37% decrease in the maximal respiratory capacity measured in platelets from healthy, non-preeclamptic compared with preeclamptic pregnancy (P<0.01); this relationship held true for other measurements of OCR, including basal respiration; ATP-linked respiration; respiratory control ratio (RCR); and spare respiratory capacity. RCR, a measure of mitochondrial efficiency, was significantly lower in healthy pregnant compared with non-pregnant women. In contrast with increased OCR, basal ECAR was significantly reduced in platelets from preeclamptic pregnancies compared with either normal pregnancies (−25%; P<0.05) or non-pregnant women (−22%; P<0.01). Secondary analysis of OCR revealed reduced basal and maximal platelet respiration in normal pregnancy prior to 34 weeks’ estimated gestational age (EGA) compared with the non-pregnant state; these differences disappeared after 34 weeks. Taken together, findings suggest that in preeclampsia, there exists either a loss or early (before the third trimester) reversal of a normal biologic mechanism of platelet mitochondrial respiratory reduction associated with normal pregnancy.