| 1. |
- Bachmayer, Nora, et al.
(författare)
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Women with pre-eclampsia have an altered NKG2A and NKG2C receptor expression on peripheral blood natural killer cells.
- 2009
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Ingår i: American Journal of Reproductive Immunology and Microbiology. - : Wiley. - 8755-8920 .- 1046-7408 .- 1600-0897. ; 62:3, s. 147-57
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Tidskriftsartikel (refereegranskat)abstract
- PROBLEM: Preeclampsia, a pregnancy disorder, is associated with exaggerated inflammation and increased serum monokines. Uterine natural killer (NK) cells are implicated in preeclampsia pathology, but little is known regarding peripheral NK cells in the disease. METHOD OF STUDY: We examined blood NK cells at delivery in women with preeclampsia, in healthy pregnant women and in healthy non-pregnant blood donors as a reference. RESULTS: Although the percentages of both NKG2A- and NKG2C-positive NK cells were normal in preeclamptic women, the levels of NKG2A and NKG2C on NK cells were significantly up-regulated in these women. In vitro stimulation of PBMCs from healthy pregnant women and blood donors with monokines resulted in increased percentage of NKG2A(+) NK cells and increased NKG2A levels, while levels of NKG2C were decreased. CONCLUSIONS: Our results suggest that the peripheral NK-cell pool is skewed in preeclampsia and possibly under the influence of monokines like interleukin (IL)-15 and IL-12.
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| 2. |
- Hamad, Rangeen Rafik, et al.
(författare)
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Impaired endothelial function and elevated levels of pentraxin 3 in early-onset preeclampsia
- 2012
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 91:1, s. 50-56
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study endothelial function in relation to anti-angiogenic biomarkers and the inflammatory process in preeclampsia. Design: Observational study. Setting: Data were obtained from pregnant women who were admitted to the obstetrical ward at the Karolinska University Hospital, Solna, Stockholm, Sweden. Population. Thirty-five women with newly developed and untreated preeclampsia and 30 healthy controls. Methods: Flow-mediated dilation of the brachial artery, levels of anti-angiogenic and inflammatory markers were measured in plasma during pregnancy and 3-6 months after delivery. Main outcome measures. Flow-mediated dilation of the brachial artery, anti-angiogenic and inflammatory markers. Results: Flow-mediated dilation was decreased in the preeclamptic group at inclusion and at follow-up (p<0.05). Pentraxin 3 (PTX3) and ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) were elevated in women with preeclampsia during pregnancy (p<0.001). Furthermore flow-mediated dilation was lower and the ratio sFlt-1/PlGF and PTX3 were higher in early-onset preeclampsia than late preeclampsia (p=0.018, 0.002 and 0.039). Levels of PTX3 at inclusion correlated inversely with flow-mediated dilation at follow-up both in the preeclampsia and control groups (Spearman, r(s) =-0.47, p=0.02 and r(s) =-0.46, p=0.02 respectively). Conclusion: Impaired endothelial function and increased ratio sFlt/PlGF, elevated PTX3 is present in women with preeclampsia and is especially pronounced in women with early-onset preeclampsia.
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| 3. |
- Ostlund, Eva, et al.
(författare)
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Normalized endothelial function but sustained cardiovascular risk profile 11 years following a pregnancy complicated by preeclampsia
- 2013
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Ingår i: Hypertension Research. - : Springer Science and Business Media LLC. - 0916-9636 .- 1348-4214. ; 36:12, s. 1081-1087
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Tidskriftsartikel (refereegranskat)abstract
- Women with a history of preeclampsia are at increased risk of future cardiovascular disease. Preeclampsia is associated with elevated blood pressure, inflammation and endothelial dysfunction, and these findings remain 1 year after delivery. Whether these abnormalities persist long after delivery, and whether they may contribute to future cardiovascular disease, is not well studied. We studied 15 women with a history of preeclampsia and 16 matched controls with an uncomplicated pregnancy 11 years following the index pregnancy; all had also been previously examined at 1 year. We assessed arterial stiffness (pulse wave analysis), 24 h ambulatory blood pressure and endothelial function (forearm flow-mediated dilatation and pulse wave analysis following β receptor agonist provocation), and determined markers of glucose and lipid metabolism, inflammation and vascular function. The preeclampsia group had higher blood pressures and reduced night/day blood pressure ratios, increased body mass index and reduced glucose tolerance, and increased levels of tissue necrosis factor receptor 1 and intracellular adhesion molecule-1, suggesting inflammatory and vascular activation. However, the endothelial impairment observed in the preeclampsia group at 1 year was normalized at 11 years, whereas the control group remained unchanged during follow-up. Our findings of higher blood pressures, impaired glucose tolerance and normalization of endothelial function 11 years after preeclampsia suggest cardiovascular risk factors present already before pregnancy to be more important than permanent endothelial damage for the increased risk of future cardiovascular complications in women with a history of preeclampsia.
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| 4. |
- Rafik Hamad, Rangeen, et al.
(författare)
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Assessment of left ventricular structure and function in preeclampsia by echocardiography and cardiovascular biomarkers
- 2009
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 27:11, s. 2257-2264
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To assess left ventricular (LV) structure and function in preeclampsia, a serious vascular-related pregnancy disorder, by Doppler tissue imaging (DTI) in combination with the levels of cardiovascular biomarkers. MATERIAL AND METHODS: Thirty-five pregnant women with preeclampsia and 30 with normal pregnancy, matched for age and gestational age were examined during pregnancy and 3-6 months after delivery. Transthoracic echocardiography and DTI were performed and blood levels of amino-terminal pro-brain natriuretic peptide (NT-pro-BNP), C-reactive protein (CRP), cystatin C and troponin I were analyzed. RESULTS: There were significant differences in LV and left atrial dimensions and function between the groups. A higher septal and lateral E/E' ratio (E = early transmitral diastolic flow velocity and E' = early diastolic myocardial velocity) (P < 0.0001, 0.0008) and higher levels of NT-pro-BNP, cystatin C, and lower cystatin C estimated GFR in ml/min per 1.73 m (P < 0.0001) were seen in the preeclampsia both during pregnancy and at follow-up. In addition the levels of E/E' ratio lateral and NT-pro-BNP were higher in pregnant women with early-onset preeclampsia necessitating delivery before 34 weeks of gestation than those who developed preeclampsia and delivered at or after 34 weeks (P = 0.0004, 0.005). CONCLUSION: In pregnancies complicated by preeclampsia, especially early-onset preeclampsia, the diastolic LV function is impaired and levels of biomarkers, NT-pro-BNP and cystatin C, are increased in comparison to normal pregnancy.
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| 5. |
- Rafik Hamad, Rangeen
(författare)
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Cardiovascular function and biomarkers in women with preeclampsia
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Preeclampsia (PE) is a multisystem disorder peculiar to human pregnancy and characterized by the onset of hypertension and proteinuria after the 20th week of gestation. The pathophysiology of this disorder is still not clear. PE is not only associated with significant maternal and fetal morbidity and mortality during the index pregnancy but also with higher risk of cardiovascular disease later in life. Overall aim: To study PE-related changes in the function of cardiovascular system and to measure the levels of different biomarkers of PE during pregnancy and after delivery. Papers I and II: Eighteen women with a history of PE and 17 age-matched controls were enrolled one year after the index pregnancy. All underwent non-invasive ultrasound examination of the brachial artery for evaluation of flow-mediated vasodilatation (FMD). Ambulatory blood pressure and plasma concentrations of lipoproteins, inflammation markers, adhesion molecules, glucometabolic and hemostatic factors, thrombin generation and the levels of microparticles were determined during specific menstrual phases. Women with a history of PE had lower FMD, higher systolic, diastolic and mean arterial pressure during daytime, and a higher degree of insulin resistance. In addition they had a higher total amount of thrombin and platelet-derived microparticles, with no variation during follicular and luteal phases. Papers III and IV: Thirty-five pregnant women with PE and 30 with normal pregnancy were examined during pregnancy and 3-6 months after delivery. Transthoracic echocardiography and Doppler tissue imaging were performed, and FMD of the brachial artery was examined. The blood levels of amino-terminal pro-brain natriuretic peptide (NT-pro-BNP), C-reactive protein, cystatin C, troponin I and inflammatory and angiogenic markers were measured. Women with PE showed structural and functional alterations in left ventricle and left atrium. They had a higher ratio of early transmitral diastolic flow velocity to early diastolic myocardial velocity (E/E), higher levels of NT-pro-BNP and cystatin C, and lower glomerular filtration rate as estimated using cystatin C both during pregnancy and at follow-up. In addition, the lateral E/E ratio and NT-pro-BNP were higher in women with early-onset, severe PE than in those with late PE. The FMD was decreased in the preeclamptic group at inclusion and at follow-up. Pentraxin 3 (PTX3) and ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (P1GF) were elevated in women with PE pregnancy. Furthermore FMD was lower and PTX3 and ratio of sFlt-1/P1GF were higher in women with early-onset, severe PE than in those with late PE. Conclusion: Women with a history of PE had persisting identifiable abnormalities of vascular function as well as signs of hypercoagulability and excess platelet-derived microparticles, during both follicular and luteal phases of the menstrual cycle. PE was associated with alterations in the left ventricular structure and function, impaired endothelial function and elevation of cardiovascular biomarkers. These alterations persisted months after delivery and were more clearly visible in women with early-onset and severe PE. In addition, elevated inflammatory and antiangiogenic markers were present in those women, and were especially pronounced in early-onset PE.
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| 6. |
- Sohlberg, Ebba, et al.
(författare)
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Pre-Eclampsia Affects Cord Blood NK Cell Expression of Activation Receptors and Serum Cytokine Levels but Not CB Monocyte Characteristics
- 2014
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Ingår i: American Journal of Reproductive Immunology. - : Wiley. - 1046-7408 .- 1600-0897. ; 71:2, s. 178-188
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Tidskriftsartikel (refereegranskat)abstract
- ProblemMaternal immunopathology in pre-eclampsia is well studied; however, less is known regarding the immunological effects on the newborns. Increased inflammation and activation of immune cells at the fetal-maternal interface in pre-eclampsia could influence the neonatal immune compartment. Method of StudyMonocytes and natural killer (NK) cells from cord blood (CB) of children with pre-eclamptic or healthy mothers were analyzed by flow cytometry for surface markers and intracellular cytokines. In addition, serum cytokine profiles were investigated using ELISA or cytometric bead array. ResultsNeonates born to pre-eclamptic mothers had an inflammatory serum cytokine profile. While CB monocyte characteristics seemed unaffected, CB NK cells from pre-eclamptic pregnancies had higher NKp30, but borderline lower NKG2D expression. ConclusionIn utero inflammatory priming of neonatal innate immunity taking place in pre-eclamptic pregnancies might influence specific NK cell functions in newborns.
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