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Biomedical subjects

Jane E Ramsay

Publications and source records attributed to Jane E Ramsay.

9 recordsLinked to original sources
PubMed2006

Longitudinal assessment of maternal endothelial function and markers of inflammation and placental function throughout pregnancy in lean and obese mothers.

BACKGROUND: Obesity in pregnancy is increasing and is a risk factor for metabolic pathology such as preeclampsia. In the nonpregnant, obesity is associated with dyslipidemia, vascular dysfunction, and low-grade chronic inflammation. AIM: Our aim was to measure microvascular endothelial function in lean and obese pregnant women at intervals throughout their pregnancies and at 4 months after delivery. Plasma markers of endothelial function, inflammation, and placental function and their association with microvascular function were also assessed. METHODS: Women in the 1st trimester of pregnancy were recruited, 30 with a body mass index (BMI) less than 30 kg/m(2) and 30 with a BMI more than or equal to 30 kg/m(2) matched for age, parity, and smoking status. In vivo endothelial-dependent and -independent microvascular function was measured using laser Doppler imaging in the 1st, 2nd, and 3rd trimesters of pregnancy and at 4 months postnatal. Plasma markers of endothelial activation [soluble intercellular cell adhesion molecule-1 (sVCAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWF), and plasminogen activator inhibitor (PAI)-1], inflammation (IL-6, TNFalpha, C-reactive protein, and IL-10), and placental function (PAI-1/PAI-2 ratio) were also assessed at each time point. RESULTS: The pattern of improving endothelial function during pregnancy was the same for lean and obese, but endothelial-dependent vasodilation was significantly lower (P < 0.05) in the obese women at each trimester (51, 41, and 39%, respectively). In the postpartum period, the improvement in endothelial-dependent vasodilation persisted in the lean women but declined to near 1st trimester levels in the obese (lean/obese difference, 115%; P < 0.01). There was a small but significant difference in endothelial-independent vasodilation between the two groups, lean response being greater than obese (P = 0.021), and response declined in both groups in the postpartum period. In multivariate analysis, time of sampling had the most impact on endothelial-independent function [18.5% (adjusted sum of squares expressed as a percentage of total means squared), P < 0.001 for sodium nitroprusside response; 9.8%, P < 0.001 for acetylcholine response], and obesity had the most impact on endothelial-dependent microvascular function (1.7%, P = 0.046 for sodium nitroprusside response; 19.3%, P < 0.001 for acetylcholine response). Time of sampling (11.2%, P < 0.001), IL-6 (4.0%, P = 0.002), and IL-10 (2.4%, P = 0.018) were significant independent contributors to variation in endothelial-dependent microvascular function. When obesity was entered into the model, the association with IL-6 and IL-10 was no longer significant, and obesity explained 6.8% (P < 0.001) of the variability in endothelial-dependent microvascular function. In the 1st trimester, obese women had a significantly higher PAI-1/PAI-2 ratio [obese median (interquartile range), 0.87 (0.54-1.21) vs. lean 0.30 (0.21-0.47), P < 0.001), reflecting the lower PAI-2 levels in obese pregnant women. In a multivariate analysis, 1st trimester BMI (7.6%, P = 0.012), IL-10 (8.2%, P < 0.001), and sVCAM-1 (0.73%, P = 0.007) contributed to the 1st trimester PAI-1/PAI-2 ratio. CONCLUSION: Obese mothers have a lower endothelium-dependent and -independent vasodilation when compared with lean counterparts. There was a higher PAI-1/ PAI-2 ratio in the 1st trimester in obese women, which improved later in pregnancy. Obese pregnancy is associated with chronic preexisting endothelial activation and impairment of endothelial function secondary to increased production of inflammatory T-helper cells-2 cytokines.

Acetylcholine↗
PubMed2004

Short- and long-term changes in plasma inflammatory markers associated with preeclampsia.

Preeclampsia is characterized by hypertension, dyslipidemia, and increased systemic inflammatory response and has been associated with an increased maternal risk of cardiovascular disease later in life. Low-grade chronic inflammation is a risk factor for cardiovascular disease. This study examined changes in inflammatory markers prospectively during pregnancy, the current inflammatory status of women who had a pregnancy complicated by preeclampsia 20 years previously against matched controls, and the association between inflammatory genes and risk of preeclampsia in a case (n=106) control (n=212) study. In control pregnancies (n=34), mean interleukin-10 (IL-10) levels increased 38% (P=0.012) and tumor necrosis factor-alpha (TNF-alpha) by 33% (P=0.024) between the first and third trimesters. The mean preeclampsia group IL-10 and TNF-alpha rose by 43% (P=0.013 and P=0.0065, respectively) from the first to the third trimester. In women with preeclampsia only, plasma IL-6 increased from the first to the third trimester (1.66 [2.04] to 2.94 [2.47] pg/mL; P=0.0004). Twenty years after the index pregnancy, women who had had preeclampsia demonstrated significantly higher IL-6 to IL-10 ratio (3.96 [6.07] versus 2.12 [1.89]; P=0.034) compared with a healthy index pregnancy 20 years previously, that persisted after adjustment for smoking and current body mass index. The IL-1beta (C-511T), IL-6 (G-174C), TNF-alpha (G-308A), E-selectin (S128R), intercellular adhesion molecule-1 (K469E), and C-reactive protein (C1059G) polymorphisms were not associated with risk of developing preeclampsia. In conclusion, preeclampsia is associated with short- and long-term changes in inflammatory status.

Adult↗
PubMed2004

Divergent metabolic and vascular phenotypes in pre-eclampsia and intrauterine growth restriction: relevance of adiposity.

OBJECTIVE: Pre-eclampsia (PE) and intrauterine growth restriction (IUGR) may both arise secondary to inadequate trophoblast invasion. Maternal vascular disease is evident only in PE. Little mechanistic evidence exists to explain this dichotomy. METHODS: We employed laser Doppler imaging (LDI) to examine microvascular function in 15 women with PE and 30 healthy pregnant women matched for body mass index (BMI). We also examined 16 women with IUGR. Other factors examined included indices of inflammation, lipoproteins, leptin and insulin concentrations. RESULTS: Women with PE had double the concentration of leptin and 30% higher triglyceride than controls. Vascular cell adhesion molecule (VCAM)-1 and interleukin (IL)-6 were also higher in women with PE, with both factors correlating with leptin independently of BMI. No difference in microvascular reactivity was observed between controls and women with PE. Women with IUGR had a four-unit smaller BMI than women with PE. When compared with controls, they also had lower low-density lipoprotein cholesterol (LDL-C) concentrations and systemic inflammatory measures were not elevated. CONCLUSIONS: The technique of LDI is not sensitive to the vascular dysfunction of PE. However, circulating endothelial-derived factors are elevated in association with markedly elevated leptin levels. Therefore, women with IUGR may demonstrate a protective role for their 'leanness' with regard to maternal systemic inflammatory effect.

Adipose Tissue↗
PubMed2003

Paradoxical elevation in adiponectin concentrations in women with preeclampsia.

Adiponectin is a recently identified, insulin-sensitizing and anti-inflammatory protein released by adipocytes, which is paradoxically reduced in obesity. It suppresses endothelial activation. Physiological insulin resistance occurs in normal pregnancy and is exaggerated in women with preeclampsia (PE), together with enhanced inflammatory and endothelial activation. Women with increased body mass index (BMI) and insulin resistance are predisposed to PE. We hypothesized that adiponectin concentrations are reduced in normal pregnancy compared with postpartum values and further reduced in women with PE. Fifteen women with PE and 30 control subjects with similar first trimester BMI had adiponectin concentrations measured in the third trimester; postpartum measurements were repeated in 16 control subjects. Adiponectin concentration in healthy pregnant women correlated inversely with early pregnancy BMI (r=-0.47, P=0.01) and fasting insulin concentrations (r=-0.58, P=0.001). However, adiponectin concentrations did not differ significantly in pregnancy and postpartum samples (mean change, -0.15 microg/mL; 95% CI, -2.28 to 1.98, P=0.88). Plasma adiponectin concentrations were markedly elevated (P=0.01) in women with PE (mean, 21.6; SD, 8.18 microg/mL) compared with control subjects (mean, 14.7; SD, 7.06 microg/mL). Moreover, in PE, adiponectin concentrations did not correlate with first trimester BMI or insulin or with serum urate or creatinine concentrations or urinary protein levels. We conclude that plasma adiponectin concentrations are not elevated in normal human pregnancy and paradoxically elevated (by 47%) in women with PE. This may be secondary to exaggerated nonspecific adipocyte lipolysis or as a physiological response to enhance fat utilization and attenuate endothelial damage. Future studies should determine whether adiponectin concentrations help improve prediction of PE.

Adiponectin↗
PubMed2003

Enhancement of endothelial function by pregnancy: inadequate response in women with type 1 diabetes.

OBJECTIVE: Pregnant women with type 1 diabetes have a substantially increased risk of vascular complications. Our aim was to study vascular function and metabolic and inflammatory risk factors during the antenatal and postpartum periods in women with type 1 diabetes compared with healthy control subjects. RESEARCH DESIGN AND METHODS: A total of 15 women with diabetes and 30 control subjects were recruited in the third trimester of pregnancy. Of these women, 9 case subjects and 16 control subjects were reinvestigated in the postnatal period. Blood samples were collected and microvascular skin perfusion was assessed in vivo using laser Doppler imaging and iontophoretic administration of endothelial-dependent (acetylcholine [ACH]) and endothelial-independent (sodium nitroprusside [SNP]) vasodilators. RESULTS: Microvascular responses in both control subjects (ACH, P = 0.018; SNP, P = 0.01) and diabetic women (ACH, P = 0.029; SNP, P = 0.105) were better during pregnancy than in the postnatal period, although responses in women with diabetes were significantly inferior to those in control subjects during both periods (all P < 0.001, two-way ANOVA). This dysfunction existed despite similar lipoprotein profiles. The difference in vascular responsivity between case and control subjects was significantly attenuated by adjustment for differences in HbA(1c) but not C-reactive protein concentrations in the two groups. CONCLUSIONS: Pregnancy enhances microvascular function, but in women with diabetes, such improvements are insufficient to attain responses seen in healthy nonpregnant women. This suggests a persistent vascular defect in young women with type 1 diabetes that may contribute to adverse pregnancy outcome. Our data suggest a role for the chronic effects of hyperglycemia in the impaired vascular responsiveness in such women.

Acetylcholine↗
PubMed2003

Microvascular dysfunction: a link between pre-eclampsia and maternal coronary heart disease.

Epidemiological studies have recently demonstrated a relationship between pre-eclampsia and coronary heart disease. Insulin resistance has been implicated as a common factor. We have demonstrated, for the first time, using laser Doppler imaging in vivo, impaired microvascular function in women 15-25 years following a pregnancy complicated by pre-eclampsia. Thus, microvascular dysfunction, which is associated with insulin resistance, may be a predisposing vascular mechanism for both coronary heart disease and pre-eclampsia. Pregnancies complicated by pre-eclampsia may identify women at risk of vascular disease in later life and may provide the opportunity for lifestyle and risk factor modification to alter maternal vascular disease risk.

Adult↗
PubMed2002

Maternal obesity is associated with dysregulation of metabolic, vascular, and inflammatory pathways.

Obesity is increasing in prevalence worldwide and in all age groups. In nonpregnant individuals, obesity is associated with dyslipidemia; hyperinsulinemia; vascular dysfunction; and, more recently, low-grade chronic inflammation. However, whether such effects are sustained during pregnancy has been sparsely investigated but is important to establish, given the association of maternal obesity with numerous adverse metabolic and vascular consequences. We consecutively recruited 47 healthy women in the third trimester of pregnancy and divided the participants into 2 groups, lean [n = 24; median body mass index (BMI), 22.1 kg/m(2)] and obese (n = 23; median BMI, 31.0 kg/m(2)) around the median first trimester BMI. The age, parity, and smoking history were comparable in both groups. A detailed panel of metabolic and inflammatory parameters was measured and an in vivo assessment of endothelial-dependent and -independent microvascular function made using laser doppler imaging. Although low-density lipoprotein cholesterol and glycosylated hemoglobin were similar, fasting triglyceride concentrations were higher [2.70 (interquartile range, 2.3-3.21) vs. 2.20 (IQ range, 2.0-2.6) mmol/liter, P = 0.02] and high-density lipoprotein concentrations were lower [1.55 (IQ range, 1.1-1.7) vs. 1.72 (IQ range, 1.4-2.0) mmol/liter, P = 0.02] in the obese group. Leptin [55.6 (range, 45-64.4) ng/ml vs. 23.8 (range, 13.2-35.2) ng/ml, P < 0.0001] and fasting insulin [14.5 (range, 11.4-27.3) vs. 6.5 (range, 4.6-9.7) mU/liter, P < 0.0001] levels were more than double. Similarly, levels of inflammatory parameters, IL-6 [3.15 (range, 2.4-3.5) vs. 2.1 (range, 1.73-2.85) pg/ml, P = 0.003], and sensitive C-reactive protein [4.45 (range, 2.9-6.6) vs. 2.25 (range, 0.92-3.65) mg/ml, P = 0.0015] were also substantially elevated. Both endothelial-dependent and -independent vasodilatory responses were significantly reduced in the obese group (P = 0.0003 and P = 0.02, respectively, ANOVA) and systolic blood pressure was higher (P = 0.01). Metabolic factors, C-reactive protein (r = 0.289, P = 0.049), and insulin (r = 0.339, P = 0.02) were related inversely to endothelial-dependent function. These comprehensive data demonstrate that, as in nonpregnant obese individuals, obesity in pregnancy is associated not only with marked hyperinsulinemia (without necessarily glucose dysregulation) and dyslipidemia but also impaired endothelial function, higher blood pressure, and inflammatory up-regulation. Such a spectrum of risk factors may contribute to maternal complications in obese women and, as a result, influence fetal programming of adult vascular disease. Clearly, these data provide further rationale to examine the potential benefits of preconceptual weight loss and antenatal exercise.

Adult↗
PubMedDate not supplied

Elimination of electrically induced iontophoretic artefacts: implications for non-invasive assessment of peripheral microvascular function.

Iontophoretic assessment of skin microvascular function is complicated by the occurrence of electrically induced hyperaemia, especially at the cathode. Studies were performed to identify means of reducing such effects. Skin vasodilator responses were measured using a laser Doppler imager that controlled iontophoretic current delivery. A novel feature involved monitoring voltage across the iontophoresis chambers. Comparison between responses to vehicle (distilled H(2)O), acetylcholine (ACh) and sodium nitroprusside (SNP) showed electrically induced hyperaemia at the cathode associated with the vehicle, whose time course overlapped with that of the SNP response. Voltage across the chambers containing drugs dissolved in H(2)O was significantly (p = 0.018, n = 7) lower than the voltage profile of H(2)O alone. H(2)O iontophoresis was associated with cathodal hyperaemic responses in most subjects, whereas a 0.5% NaCl vehicle produced lower voltages and eliminated this artefact. Voltage.time integral rather than charge was the prime determinant of electrically induced hyperaemic responses. No significant correlation was found between skin fold thickness and either calculated skin resistance (r(2) = 0.0002) or vascular response to ACh (r(2) = 0.13). Smaller chamber size led to higher voltages and greater electrically induced hyperaemic responses. These appear to be prostaglandin dependent as they were ablated by cyclooxygenase inhibition. Use of a low-resistance vehicle combined with larger chamber sizes and lower currents can prevent such artefacts, thereby increasing the robustness of this methodology for clinical assessment of endothelial function.

Acetylcholine↗