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.

Rapid kinetics of changes in oxygen consumption rate in thrombin-stimulated platelets measured by high-resolution respirometry

“…The Seahorse XF has been used to characterise platelet O 2 consumption, mitochondrial function and glycolysis. This has usually been studied in unstimulated platelets, either from healthy donors [ [9] , [10] , [11] ], or from patients with conditions such as sickle cell disease [ 12 ], pulmonary hypertension [ 13 ], type 2 diabetes [ 14 ] or preeclampsia [ 15 ]. A small number of studies have reported changes in platelets following stimulation with thrombin, which increased O 2 consumption rate by approximately 25% at the next measured time (approximately 8 min later) [ 3 , 16 ].…”

Effect of Low-Dose Persistent Organic Pollutants on Mitochondrial Function: Human and in Vitro Evidence

“…Although mitochondrial function varies among individuals and both genetic and environmental factors contribute to their variability, the mitochondrial function of an individual is also flexible and adaptable to meet the energy demands of a particular cell type under quiescent conditions and during biological activation [30]. For example, OCR levels in peripheral blood cells among patients with certain mitochondrial dysfunction-related dis-eases, such as sickle cell anemia, autism, acute pancreatitis, and septic shock, were compared with those of control groups in small-scale clinical studies [8][9][10][11]13]. The results demonstrated that OCR levels of patient groups were not consistently lower than those of control groups.…”

“…For epidemiological studies that have practical limitations concerning the availability of bio-specimens, OCR levels of leukocytes and platelets can be used as a surrogate marker to investigate mitochondrial function in humans [7]. Several small-scale clinical studies have measured the OCR of leukocytes or platelets to compare OCR levels between patients and control groups [8][9][10][11][12][13].…”

Sample Preparation as a Critical Aspect of Blood Platelet Mitochondrial Respiration Measurements—The Impact of Platelet Activation on Mitochondrial Respiration

“…Our results show that the use of EDTA not only led to a significant platelet activation, but also to increase in dissipative component of respiration, which is not accessible to perform biochemical work (LEAK). The EDTA is known for its negative effects on platelet activation [21,22], and despite this, it is still the most commonly used anticoagulant in platelet mitochondrial respiration studies [7,[23][24][25][26][27]. While little research appears to have been performed on the effect of anticoagulants on platelet mitochondrial respiration, Kramer and colleagues reported that neither anticoagulant citrate-dextrose solution (ACD) nor EDTA had any effect on the bioenergetic function of platelets; however, no supporting data were given [28].…”