Increased circulating oxidised low-density lipoprotein and antibodies to oxidised low-density lipoprotein in preeclampsia

Arifin, Rosemawati; Kyi, Win Mar; Yaakob, Che Anuar Che; Yaacob, Najib Majdi

doi:10.1080/01443615.2016.1269227

Cited by 14 publications

(8 citation statements)

References 24 publications

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“…This is in line with previous data assessing the effect of oxLDL on vascular function in rat, mouse and human arteries 2,14,23,31 , and confirms that the overexpression of LOX-1 in the LOX-1tg mice is functional. Aside from being a well-known ligand for LOX-1, oxLDL is also a circulating factor that is increased in complicated pregnancies, such as preeclampsia 15,16 . Our data confirm our hypothesis that specifically in conditions of increased LOX-1 expression oxLDL reduces endothelium-dependent vasodilation and may thus contribute to systemic vascular dysfunction that is observed in women with preeclampsia.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, pregnancy complications such as preeclampsia have also been associated with endothelial dysfunction and placental and vascular oxidative stress 14 . Some reports have shown that oxLDL levels are higher in women with preeclampsia and have been associated with an increased risk for developing preeclampsia 15,16 . Moreover, LOX-1 expression was shown to be increased in omental arteries from women with preeclampsia, as well as in aortas from pregnant rats with reduced perfusion pressure, suggesting a potential role for LOX-1 in complicated pregnancies 4,5 .…”

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confidence: 99%

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Role of Lectin-like Oxidized LDL Receptor-1 and Syncytiotrophoblast Extracellular Vesicles in the Vascular Reactivity of Mouse Uterine Arteries During Pregnancy

Spaans

Quon

Kirschenman

et al. 2020

Sci Rep

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Vascular complications in pregnancy (e.g. preeclampsia) are a major source of maternal and foetal morbidity and mortality, and may be due to excessive release of placental syncytiotrophoblast-derived extracellular vesicles (STBEVs) into the maternal circulation. Increased activity of the multi-ligand scavenger receptor Lectin-like Oxidized LDL Receptor-1 (LOX-1) is associated with vascular dysfunction, and LOX-1 has been shown to interact with angiotensin II receptor type 1 (AT1). We hypothesized that STBEVs contribute to vascular dysfunction via LOX-1 and AT1 receptors during pregnancy. Uterine arteries from late pregnant wildtype and LOX-1 overexpressing mice were incubated overnight with or without STBEVs and vascular function was assessed using wire myography. STBEV-incubation decreased angiotensin II responsiveness only in wildtype mice, which coincided with decreased AT1 contribution and expression. Thus, STBEVs reduced angiotensin II responsiveness in normal pregnancy, but not in conditions of increased LOX-1 expression, suggesting that STBEVs (via LOX-1) play a role in normal adaptations to pregnancy. Oxidized LDL (a LOX-1 ligand) increased angiotensin II-induced vasoconstriction in STBEV-incubated arteries from both mouse strains, suggesting that the LOX-1 pathway may be involved in complicated pregnancies with elevated STBEVs and oxidized LDL levels (such as preeclampsia). These data increase our understanding of vascular complications during pregnancy. oxLDL increased Ang II responses in STBEV-incubated arteries. Pre-incubation with oxLDL (i.e. LOX-1 activation) decreased Ang II responsiveness in control uterine arteries from both WT and LOX-1tg mice (Fig. 6a,b). However, in uterine arteries pre-incubated with STBEVs, oxLDL increased Ang II responsiveness in both WT and LOX-1tg mice compared with control arteries (Fig. 6c). Scientific RepoRtS |(2020) 10:6046 | https://doi.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Role of Lectin-like Oxidized LDL Receptor-1 and Syncytiotrophoblast Extracellular Vesicles in the Vascular Reactivity of Mouse Uterine Arteries During Pregnancy

Spaans

Quon

Kirschenman

et al. 2020

Sci Rep

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“…Previous studies (8,9) have highlighted that the oxidation of low-density lipoprotein (LdL) leads to upregulation of the levels of inflammatory factors, including tumor necrosis factor-α and interleukin-6, in the body, and may decrease the cell invasive ability of trophoblasts and promote cell apoptosis, thereby resulting in abnormal development of placenta and the occurrence of PE. According to the National center for Biotechnology Information (NcBI) database, LdL receptor-related protein 6 (LRP6) is highly expressed in placental tissues.…”

Section: Introductionmentioning

confidence: 99%

LRP6 is involved in the proliferation, migration and invasion of trophoblast cells via miR‑346

Zhang

et al. 2020

Int J Mol Med

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Low-density lipoprotein receptor-related protein 6 (LRP6) promotes metastasis in numerous types of cancer; however, its role in trophoblast cells has been less frequently reported. In the present study, the effects of up-and downregulation of LRP6 on trophoblast cells were investigated accordingly. The study aimed to develop a therapeutic target for gestational choriocarcinoma. The expression levels of LRP6 in pre-eclampsia (PE) tissues, trophoblast cell lines and gestational choriocarcinoma cells were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPcR) assay. double-luciferase reporter analysis was conducted to detect the regulatory gene of LRP6. Furthermore, the proliferative, migratory and invasive abilities of trophoblasts and gestational choriocarcinoma cells were determined by ccK-8, wound healing, and Transwell assays, respectively. The expression levels of the genes and proteins of interest [matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2] associated with tumor cell invasion were measured by performing RT-qPcR and western blotting, respectively. The National center for Biotechnology Information database revealed that LRP6 was relatively highly expressed in placental tissues, but was poorly expressed in PE tissues and trophoblast cell lines. The upregulation of LRP6 not only increased the activity, migration and invasion of trophoblast cells, but it also promoted the expression of MMP-2 and MMP-9, whereas it inhibited the expression levels of TIMP-1 and TIMP-2. Such results followed the opposite trend to those of downregulation of LRP6 in gestational choriocarcinoma cells. Moreover, LRP6 was predicted to be the target gene for microRNA (miR)-346, which was highly expressed in PE tissues and trophoblast cell lines. The present study also revealed that LRP6 could reverse the effects of miR-346 on the proliferation, migration and invasion of trophoblast cells. Therefore, considered collectively, the results of the present study have demonstrated that LRP6 is involved in the proliferation, migration and invasion of trophoblast cells via miR-346, and that LRP6 may serve as a potential target in cancer treatment.

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“…38,39 One mechanism suggested to affect the BBB includes increased levels of oxidized low-density lipoprotein (oxLDL) in women with preeclampsia. 40,41 Increased oxidative stress in the placental circulation during preeclampsia causes oxidative conversion of LDL to oxLDL. oxLDL initiates multiple pathways in both endothelial and vascular smooth muscle cells, mostly through binding to its receptor lectinlike oxLDL receptor (LOX-1).…”

Section: Pathophysiologymentioning

confidence: 99%

Eclampsia in the 21st century

Bartal

Sibai

2022

American Journal of Obstetrics and Gynecology

119

142

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Definition and IncidenceEclampsia is one of the most serious acute complications of pregnancy, and it carries high morbidity and mortality for both the mother and baby. 1 Eclampsia is defined as the occurrence of 1 or more generalized, tonic-clonic convulsions unrelated to other medical conditions in women with hypertensive disorder of pregnancy. Although 10% of pregnancies are complicated by hypertensive disorders, eclampsia continues to occur in 0.8% of women with hypertensive disorders. 2 During the past 50 years, there has been a reduction in the rate of eclampsia in developed countries with a reported incidence ranging from 1.6 per 10,000 deliveries to 10 per 10,000 deliveries. 3e13 In some low-resource or developing countries, the reported rate of eclampsia ranges from 50 to 151 per 10,000 deliveries (Figure 1). 14e18 Although the rate of eclampsia and the number of maternal deaths from hypertension in pregnancy have fallen steadily over recent years in developing countries, hypertensive disorders still feature among the top 6 causes of maternal mortality in the United States and are responsible for up to 14% of all maternal deaths worldwide. 1,19e21 Our impression is that differences in the incidence and complication rates between developed and developing countries result from gaps in access to care, appropriate and early prenatal care, surveillance and management protocols for timely hospitalization and delivery, antihypertensive therapy for prevention of stroke, pulmonary edema, congestive heart failure and magnesium sulfate prophylaxis during the peripartum period in women with severe preeclampsia. 22,23

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Increased circulating oxidised low-density lipoprotein and antibodies to oxidised low-density lipoprotein in preeclampsia

Cited by 14 publications

References 24 publications

Role of Lectin-like Oxidized LDL Receptor-1 and Syncytiotrophoblast Extracellular Vesicles in the Vascular Reactivity of Mouse Uterine Arteries During Pregnancy

Role of Lectin-like Oxidized LDL Receptor-1 and Syncytiotrophoblast Extracellular Vesicles in the Vascular Reactivity of Mouse Uterine Arteries During Pregnancy

LRP6 is involved in the proliferation, migration and invasion of trophoblast cells via miR‑346

Eclampsia in the 21st century

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