Preeclampsia is a pregnancy-specific hypertensive syndrome that causes substantial maternal and fetal morbidity and mortality. Maternal endothelial dysfunction mediated by excess placenta-derived soluble VEGF receptor 1 (sVEGFR1 or sFlt1) is emerging as a prominent component in disease pathogenesis. We report a novel placenta-derived soluble TGF-beta coreceptor, endoglin (sEng), which is elevated in the sera of preeclamptic individuals, correlates with disease severity and falls after delivery. sEng inhibits formation of capillary tubes in vitro and induces vascular permeability and hypertension in vivo. Its effects in pregnant rats are amplified by coadministration of sFlt1, leading to severe preeclampsia including the HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome and restriction of fetal growth. sEng impairs binding of TGF-beta1 to its receptors and downstream signaling including effects on activation of eNOS and vasodilation, suggesting that sEng leads to dysregulated TGF-beta signaling in the vasculature. Our results suggest that sEng may act in concert with sFlt1 to induce severe preeclampsia.

Abstract-Preeclampsia is a major cause of maternal, fetal, and neonatal mortality worldwide. Although the etiology of preeclampsia is still unclear, recent studies suggest that its major phenotypes, high blood pressure and proteinuria, are due in part to excess circulating soluble fms-like tyrosine kinase-1 concentrations. Soluble fms-like tyrosine kinase-1 is an endogenous antiangiogenic protein that is made by the placenta and acts by neutralizing the proangiogenic proteins vascular endothelial growth factor and placental growth factor. High serum soluble fms-like tyrosine kinase-1 and low serum free placental growth factor and free vascular endothelial growth factor have been observed in preeclampsia. Abnormalities in these circulating angiogenic proteins are not only present during clinical preeclampsia but also antedate clinical symptoms by several weeks. Therefore, this raises the possibility of measuring circulating angiogenic proteins in the blood and the urine as a diagnostic and screening tool for preeclampsia. The availability of a test to predict preeclampsia would be a powerful tool in preventing preeclampsia-induced mortality, especially in developing nations, where high-risk specialists are limited. This review will summarize our current understanding of the role of circulating angiogenic proteins in the pathogenesis and clinical diagnosis/prediction of preeclampsia.

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REECLAMPSIA IS A COMMON HYpertensive disorder of pregnancy characterized by systemic endothelial dysfunction and diagnosed by the appearance of hypertension and proteinuria. 1,2 For this reason, it is recommended that women undergo blood pressure and urinary protein screening at each prenatal visit throughout gestation. 3 Potentially lifethreatening complications of preeclampsia include seizures, cerebral hemorrhage, disseminated intravascular coagulation, and renal failure; and the time between the first detection of hypertension and proteinuria and the subsequent development of these complications can be extremely short. 3,4 The only known cure for preeclampsia is delivery of the placenta. If maternal signs develop before the fetus is mature, the risk of neonatal morbidity and mortality due to premature delivery is markedly increased. Evidence from our group and others suggests that preeclampsia may be caused by an imbalance of angiogenic factors. 5-12 Circulating soluble fms-like tyrosine kinase 1 (sFlt1, also referred to as sVEGFR1), an antiangiogenic protein, binds the proangiogenic proteins, vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), preventing their interac

Altered angiogenesis and insulin resistance are associated with preeclampsia and cardiovascular disease (CVD), and women with preeclampsia appear to be at increased risk of future CVD. We hypothesized that these factors are detectable in asymptomatic postpartum women with a history of preeclampsia and may represent pathophysiological mechanisms bridging preeclampsia and future CVD. We measured fasting insulin, glucose, vascular endothelial growth factor, and its circulating inhibitor, soluble fms-like tyrosine kinase (sFlt-1) in 29 normotensive women with a history of preeclampsia and 32 women with prior normotensive pregnancies at 18.0 +/- 9.7 months postpartum. The homeostasis model of insulin resistance (HOMA(IR)) [(insulin [microunits per milliliter] x glucose [millimoles per liter])/22.5] was calculated. Compared with women with normal pregnancies, women with prior preeclampsia had significantly increased levels of sFlt-1 (41.6 +/- 6.7 vs. 30.4 +/- 10.2; P < 0.01) and median HOMA(IR) (2.8 vs. 1.9; P = 0.04). Membership in the upper quartile of either sFlt-1 or HOMA(IR) was associated with prior preeclampsia (odds ratio 5.7; 95% confidence interval 1.7, 20.0; P < 0.01), and all five women in the upper quartiles of both sFlt-1 and HOMA(IR) had a history of preeclampsia. Women with a history of preeclampsia demonstrate altered expression of angiogenesis-related proteins and increased HOMA(IR) more than 1 yr postpartum. These factors may contribute to their risk of future CVD.

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Background During COVID-19, the public actively sought non-pharmacological and self-management approaches to prevent infection. Little is known on the use of traditional, complementary and integrative medicine (TCIM) by the public as preventive measures. This study investigated the prevalence and patterns of TCIM use during the pandemic, and identified factors associated with its use among the general population in Hong Kong. Methods An online cross-sectional survey was conducted from November to December 2020. The survey solicited information on the respondents’ sociodemographic characteristics, risk perception of the pandemic, and use of TCIM before and during the pandemic. Logistic regression analysis was conducted to determine predictors of TCIM use. Results In total, 632 responses (completion rate = 88.1%) were analyzed. TCIM was used by 44.0% of respondents during the pandemic. The most popular forms of TCIM were vitamins or other dietary supplements (n = 160, 25.3%) and Chinese herbal medicine (n = 122, 19.3%) during the pandemic. The most frequently reported indication was strengthening the immune system, especially for vitamins or other dietary supplements (n = 142/160, 88.8%). Respondents who reported using TCIM were more likely to be female (adjusted odds ratio [aOR] = 1.82, 95% confidence interval [CI] = 1.29–2.59), had higher education attainment (aOR = 2.21, 95% CI = 1.39–3.59), and older-aged (age >55 years: aOR = 1.77, 95% CI = 1.04–3.02). Respondents who resided in districts with moderate to high number of confirmed COVID-19 cases (aOR = 1.60, 95% CI = 1.07–2.42) and had a higher level of risk perception (aOR = 1.04, 95% CI = 1.01–1.07) were also more likely to use TCIM. Conclusion TCIM was used commonly in Hong Kong during the COVID-19 pandemic. While vaccination and social distancing remain the mainstay of controlling the pandemic, professional bodies should proactively consider public preferences and provide information regarding the effectiveness and safety of TCIM for COVID-19 prevention and treatment.

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