Correlation between apolipoprotein B and endothelin-1-induced vasoconstriction in humans

Low-density lipoprotein (LDL) concentrations have been linked to altered responses to endogenous vasodilators and vasoconstrictors. We evaluated retrospectively the relationship between LDL and vasoconstrictor (endothelin-1, phenylephrine) responsiveness of the forearm vasculature in 15 elderly healthy volunteers with apolipoprotein B and LDL levels in the normal range. In contrast to phenylephrine, changes in forearm vascular resistance induced by endothelin-1 were correlated with apolipoprotein B, LDL, and total cholesterol concentrations in women but not in men. These findings might suggest that lipids may increase vascular tone through both impaired endothelial vasodilation and increased vasoconstriction to endothelin-1 at least in women.     

Effects of Obesity and Body Fat Distribution on Lipids and Lipoproteins in Nondiabetic American Indians: The Strong Heart Study

Objectives: To examine the relationship between obesity and lipoprotein profiles and compare the effects of total obesity and central adiposity on lipids/lipoproteins in American Indians. Research Methods and Procedures: Participants were 773 nondiabetic American Indian women and 739 men aged 45 to 74 years participating in the Strong Heart Study. Total obesity was estimated using body mass index (BMI). Central obesity was measured as waist circumference. Lipoprotein measures included triglycerides, high‐density lipoprotei in (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol, apolipoprotein AI (apoAI), and apolipoprotein B (apoB). Partial and canonical correlation analyses were used to examine the associations between obesity and lipids/lipoproteins. Results: Women were more obese than men in Arizona (median BMI 32.1 vs. 29.2 kg/m²) and South Dakota and North Dakota (28.3 vs. 28.0 kg/m²), but there was no sex difference in waist circumference. Men had higher apoB and lower apoAI levels than did women. In women, when adjusted for center, gender, and age, BMI was significantly related to HDL cholesterol (r = ?0.24, p < 0.001). There was a significant but weak relation with apoAI (r = ?0.14 p < 0.001). Waist circumference was positively related to triglycerides (r = 0.14 p < 0.001) and negatively related to HDL cholesterol (r = ?0.23, p < 0.001) and apoAI (r = ?0.13, p < 0.001). In men, BMI was positively correlated with triglycerides (r = 0.30, p < 0.001) and negatively correlated with HDL cholesterol (r = ?0.35, p < 0.001) and apoAI (r = ?0.23, p < 0.001). Triglycerides increased with waist circumference (r = 0.30, p < 0.001) and HDL cholesterol decreased with waist circumference (r = ?0.36 p < 0.001). In both women and men there was an inverted U‐shaped relationship between obesity and waist with LDL cholesterol and apoB. In canonical correlation analysis, waist circumference received a greater weight (0.86) than did BMI (0.17) in women. However, the canonical weights were similar for waist (0.46) and BMI (0.56) in men. Only HDL cholesterol (?1.02) carried greater weight in women, whereas in men, triglycerides (0.50), and HDL cholesterol (?0.64) carried a large amount of weight. All the correlation coefficients between BMI, waist circumference, and the first canonical variable of lipids/lipoproteins or between the individual lipid/lipoprotein variables and the first canonical variable of obesity were smaller in women than in men. Triglycerides and HDL cholesterol showed clinically meaningful changes with BMI and waist circumference in men. All lipid/lipoprotein changes in women in relation to BMI and waist circumference were minimal. Discussion: The main lipoprotein abnormality related to obesity in American Indians was decreased HDL cholesterol, especially in men. Central adiposity was more associated with abnormal lipid/lipoprotein profiles than general obesity in women; both were equally important in men.     

An olive oil-rich diet results in higher concentrations of LDL cholesterol and a higher number of LDL subfraction particles than rapeseed oil and sunflower oil diets

We investigated the effect of olive oil, rapeseed oil, and sunflower oil on blood lipids and lipoproteins including number and lipid composition of lipoprotein subclasses. Eighteen young, healthy men participated in a double-blinded randomized cross-over study (3-week intervention period) with 50 g of oil per 10 MJ incorporated into a constant diet. Plasma cholesterol, triacylglycerol, apolipoprotein B, and very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) cholesterol concentrations were 10;-20% higher after consumption of the olive oil diet compared with the rapeseed oil and sunflower oil diets [analysis of variance (ANOVA), P < 0.05]. The size of IDL, VLDL, and LDL subfractions did not differ between the diets, whereas a significantly higher number (apolipoprotein B concentration) and lipid content of the larger and medium-sized LDL subfractions were observed after the olive oil diet compared with the rapeseed oil and sunflower oil diets (ANOVA, P < 0.05). Total HDL cholesterol concentration did not differ significantly, but HDL(2a) cholesterol was higher after olive oil and rapeseed oil compared with sunflower oil (ANOVA, P < 0.05).In conclusion, rapeseed oil and sunflower oil had more favorable effects on blood lipids and plasma apolipoproteins as well as on the number and lipid content of LDL subfractions compared with olive oil. Some of the differences may be attributed to differences in the squalene and phytosterol contents of the oils.     

Effects of preeclampsia and eclampsia on cord blood coagulation tests

Blood coagulation tests were determined in fifty-three paired umbilical cord blood and maternal venous blood samples originating from term singleton vaginal cephalic deliveries. The index group comprised seventeen deliveries complicated by preeclampsia or eclampsia, and the control group comprised thirty-six healthy women with uneventful pregnancies and deliveries. Mean values obtained from the coagulation and fibrinolytic assays did not significantly differ between study groups, except for antithrombin III levels in index group of neonates, which were significantly lower. Comparison of coagulation and fibrinolytic characteristics between mothers and their neonates produced expected level of difference due to immaturity of their haemostatic mechanisms. We found alterations in maternal blood coagulation and fibrinolysis and evidence of increased intravascular coagulation with severe preeclampsia and IUGR.     

Selected genetic polymorphisms and plasma coagulation factor VII changes with exercise training.

We assessed the effects of coagulation factor VII (FVII) gene polymorphisms, lipid-related polymorphisms, and exercise training-induced plasma lipoprotein lipid changes on FVII level changes with exercise training in middle- to older-aged men and women. Forty-six healthy sedentary men and women were stabilized on a low-fat diet and then underwent baseline testing, 6 mo of endurance exercise training, and final testing. Plasma FVII-Ag levels decreased with exercise training (106.7 +/- 1.4 vs. 104.2 +/- 1.6%, P = 0.005). There were no significant differences in FVII-Ag changes with exercise training between -323 (0/10 bp)/-401 (G/T) haplotype or -402 (G/A) genotype groups. FVII-Ag changes with training were not correlated with changes in plasma lipoprotein lipids. In linear regression analyses, FVII-Ag changes with training remained significant after adjusting for training-induced plasma lipoprotein lipid changes (P = 0.01). FVII changes with training were associated with apolipoprotein E genotype (P = 0.012); this relationship was still evident after adjusting for training-induced plasma lipoprotein lipid changes (P = 0.047). FVII changes with training also were significantly associated with human ATPase binding cassette-1 genotype (P = 0.018); this relationship persisted after accounting for the effect of the training-induced plasma lipoprotein lipid changes (P = 0.045). We conclude that plasma FVII-Ag changes with exercise training are more closely related to selected lipid-related genotypes than FVII gene promoter variants.     

Serum antithrombin III and alpha-2-antiplasmin concentration in patients with lung carcinoma

Serum antithrombin III and alpha-2-plasmin inhibitor concentrations has been evaluated in 26 patients with lung carcinoma. We observed a twofold decrease in antithrombin III level and no differences between test and control groups in alpha-2-plasmin inhibitor concentrations. Evidently, the decreased antithrombin III level may reflect its consumption because of enhanced plasma thrombin activity, whereas normal alpha-2-plasmin inhibitor may result in no induction of secondary fibrinolysis followed by the stimulation of the coagulation system or no conditions for primary increased fibrinolysis. It seems possible, that the antithrombin III level in the serum may at least partly reflect the tendency for hypercoagulability and spreading of cancer.     

Growth in utero and serum cholesterol concentrations in adult life.

OBJECTIVE--To see whether reduced rates of fetal growth are related to raised serum cholesterol concentrations in adult life. DESIGN--Follow up study of men and women whose size at birth had been recorded. SETTING--Jessop and Northern General Hospitals, Sheffield. SUBJECTS--219 men and women born in the Jessop Hospital during 1939-40. MAIN OUTCOME MEASURES--Serum concentrations of total cholesterol, low density lipoprotein cholesterol, and apolipoprotein B. RESULTS--Men and women who had had a small abdominal circumference at birth had raised serum concentrations of total and low density lipoprotein cholesterol and apolipoprotein B. This was independent of the duration of gestation. Serum concentrations of total cholesterol fell by 0.25 mmol/l (95% confidence interval 0.09 to 0.42) with each 1 in (2.54 cm) increase in abdominal circumference. The corresponding figure for serum low density lipoprotein cholesterol was 0.26 mmol/l (0.11 to 0.42) and for serum apolipoprotein B 0.04 g/l (0.02 to 0.07). Small head and chest circumferences at birth and short length were each associated with raised serum low density lipoprotein cholesterol concentrations but the trends disappeared in a simultaneous regression with abdominal circumference at birth. The association between abdominal circumference at birth and low density lipoprotein cholesterol concentration was independent of social class, current body weight, cigarette smoking, and alcohol consumption. CONCLUSION--Raised serum cholesterol concentrations in adult life are associated with impaired growth during late gestation, when fetal undernutrition has a disproportionate effect on liver growth. Impaired liver growth may permanently alter low density lipoprotein cholesterol metabolism.     

Alterations of lipid metabolism in men with hypotestosteronemia.

Studied relationship in serum concentration of testosterone and lipids in 35 men with a positive coronarographic finding and 30 sterile men, in comparison with a control group. From lipid parameters we determined serum concentration of cholesterol, triacylglycerols and apolipoprotein B, and lipid distribution in lipoprotein fractions. Serum testosterone concentration was found decreased in both the group as against the controls. As to lipid parameters, cholesterol concentration was depressed in the high-density lipoprotein (HDL) fraction of both the clinical groups. As increased apolipoprotein B level was seen in men with the positive coronarographic finding. The results point to a negative effect of lowered testosterone concentrations on lipid metabolism.     

Apolipoprotein E polymorphism alters the association between body fatness and plasma lipoproteins in women

The aim of the present study was to investigate the associations between total adiposity, body fat distribution, and plasma lipoprotein levels within groups of women defined on the basis of apolipoprotein E phenotypes, in order to verify whether apoE polymorphism could modify these associations. In women having only apolipoprotein E3 isoforms (n = 24), body fat mass, the waist: hip circumference ratio, and computed tomography-derived total and intra-abdominal fat areas were all positively correlated with very low density lipoprotein (VLDL) and low density lipoprotein (LDL) lipids and apolipoprotein B concentrations. These body fatness variables were also negatively correlated with plasma high density lipoprotein (HDL) cholesterol concentration. These associations were, however, altered in the groups of women carrying either apoE2 or E4 isoforms. Indeed, in women carrying the apoE2 isoform (n = 22), body fatness variables were predominantly associated with VLDL components concentration (0.05 greater than P less than 0.01) and with LDL triglyceride content. No association was found between adiposity and LDL cholesterol or apolipoprotein B levels in these women. In contrast, no relationship was found between total adiposity, regional fat accumulation, and VLDL fraction in women carrying the apolipoprotein E4 isoform (n = 17). In this latter group, computed tomography-measured total abdominal fat accumulation was positively correlated with LDL apolipoprotein B (r = 0.58, P less than 0.05) concentration, whereas intra-abdominal fat accumulation was positively correlated with both LDL cholesterol and apolipoprotein B concentrations (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Associated von Willebrand disease as a possible cause of lack of thrombosis in an AT III abnormality (AT III Trento)

In a family with a known antithrombin III abnormality (AT III Trento) an associated von Willebrand defect (Type I) was found. The two defects seem to segregate independently. In fact four types of individuals were present, namely: subjects with isolated AT III abnormality, subjects with isolated von Willebrand defect, patients with double defect and normal subjects. Only one of the two patients with isolated AT III abnormality showed a thrombotic tendency. None of the patients with double defect showed thrombotic disease, indicating a possible protective action of the von Willebrand defect against thrombotic manifestations. Patients with isolated von Willebrand defect showed neither thrombotic nor bleeding manifestations. The study emphasizes the need for a careful evaluation of the hemostatic balance of patients with AT III abnormalities before concluding that they are symptomatic or asymptomatic.     

Insulin sensitivity and regular alcohol consumption: large,prospective, cross sectional population study (Bruneck study)

OBJECTIVES: To assess the relation between regular alcohol consumption and insulin sensitivity, and to estimate the importance of insulin in the association of alcohol with multiple vascular risk factors and cardiovascular disease. DESIGN: Prospective and cross sectional study of a large randomly selected population sample. SETTING: Part of the Bruneck study 1990-5 (Bolzano province, Italy). SUBJECTS: 820 health, non-diabetic women and men aged 40-79 years. MAIN OUTCOME MEASURE: Concentrations of fasting and post-glucose insulin, cholesterol, apolipoproteins, triglycerides, Lp(a) lipoprotein glucose, fibrinogen, and antithrombin III; blood pressure; insulin resistance estimated by the homeostasis model assessment. RESULTS: Fasting insulin concentrations in those who did not drink alcohol and subjects reporting low (1-50 g/day), moderate (51-99 g/day), and heavy (> or = 100 g/day) alcohol intake were 12.4, 10.0, 8.7, and 7.1 mU/l (P < 0.001). Likewise, post-glucose insulin concentrations and estimates for insulin resistance assessed by the homeostasis model assessment decreased significantly with increasing amounts of regular alcohol consumption. These trends were independent of sex, body mass index, physical activity, cigarette smoking, medication, and diet (P < 0.001). Regular alcohol intake predicted multiple changes in vascular risk factors over a five year period including increased concentrations of high density lipoprotein cholesterol and apolipoprotein A I; higher blood pressure; and decreased concentration of antithrombin III. These associations were in part attributable to the decrease in insulin concentrations observed among alcohol consumers. CONCLUSIONS: Low to moderate amounts of alcohol, when taken on a regular basis, improve insulin sensitivity. Insulin is a potential intermediate component in the association between alcohol consumption and vascular risk factors (metabolic syndrome).     

Replacement therapy of acquired antithrombin III deficiency in experimental nephrotic syndrome

The influence of antithrombin III on hemostasis and renal function was studied in experiments on rats with nephrotic syndrome. The development of nephrotic syndrome was accompanied by the activation of blood coagulation and appearance of acquired antithrombin III deficiency due to its loss with the urine. The replacement therapy by bovine antithrombin III at a dose of 25 U/kg a day for 10 days decreased the signs of excessive thrombinogenesis in experimental animals and increased the amount of thrombin-antithrombin III complexes in the blood flow. The activation of coagulation in rats with nephrotic syndrome predominantly induced the disturbances of the excretory renal function which could be efficiently corrected by antithrombin III.     

Plasma lipids and lipoprotein cholesterol concentrations in people with different diets in Britain.

Concentrations of total cholesterol and cholesterol in the various lipoprotein fractions were measured in vegans, vegetarians, fish eaters (who did not eat meat), and meat eaters. Total and low density lipoprotein cholesterol concentrations were higher in meat eaters than vegans, with vegetarians and fish eaters having intermediate and similar values. High density lipoprotein cholesterol concentration was highest in the fish eaters but did not differ among the other groups. There were striking trends with age in total and low density lipoprotein cholesterol concentrations, which differed between men and women: women showed a steady increase in concentration with age, whereas concentrations in men did not increase appreciably after the age of 40, which may partly explain sex differences in the prevalence of coronary heart disease. The differences in total cholesterol concentration suggest that the incidence of coronary heart disease may be 24% lower in lifelong British vegetarians and 57% lower in lifelong vegans than in meat eaters.     

A residential study comparing the effects of diets rich in stearic acid, oleic acid, and linoleic acid on fasting blood lipids, hemostatic variables and platelets in young healthy men

Dietary fat is known to influence the variables of blood coagulation and fibrinolysis associated with vascular disease. However, the role of fat content and/or fat composition of the diet in this regard is still not well understood. In the present study, we investigated the effects of three isoenergic diets of differing fat composition in nine healthy young men in a strictly controlled residential study. Subjects consumed the three experimental diets for periods of 2 weeks each, separated by a washout period of at least 5 weeks in a randomized crossover design. The diets provided 38% of total energy intake as fat, 45% as carbohydrate, and 17% as protein, and differed only with respect to the fatty acid composition (stearic acid-rich diet: 34.1% stearic acid, 36.6% oleic acid; oleic acid-rich diet: 65.8% oleic acid; linoleic acid-rich diet: 36.5% linoleic acid, 38% oleic acid). Blood samples were collected at the beginning and at the end of each dietary period from fasted subjects for determination of factor VII coagulant activity (FVIIc), activated factor VII (FVIIa), factor VII antigen (FVIIag), tissue plasminogen activator (tPA) activity, plasminogen activator inhibitor type 1 (PAI-1) activity, fibrinogen, prothrombin fragment 1+2 (F(1+2)), and plasma lipids. There were no significant differences between diets in fasting plasma concentrations of FVIIc, FVIIa, FVIIag, fibrinogen, F(1+2), PAI-1 activity, and tPA activity. Plasma concentrations of lipids (high density lipoproteins, low density lipoproteins, triacylglycerols, and total cholesterol) were also unaffected. Although there were no changes in platelet aggregation response and membrane fluidity observed in any of the diets, increased anti-aggregatory prostaglandin E(1) binding to platelet membranes was observed only in the case of linoleic acid-rich diet. In conclusion, diets with very different fatty acid compositions, at 38% of energy as fat intake, did not significantly influence blood coagulation, fibrinolysis, or blood lipids in the fasting state in young healthy men.     

Plasma lipids and lipoprotein lipase activating property in women on three different combinations of estrogens and progestins

Total plasma lipoprotein lipase (LPL) activating property, triglycerides, cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured in 24 normal Venezuelan females and in 71 healthy women (20–35 years) who received one of three different combinations of ethinylestradiol and d-norgestrel for at least 6 months.Group I received a low dose combination of 30 μg ethinylestradiol plus 250 μg d-norgestrel; Group II received a high dose of 50 μg ethinylestradiol plus 250 μg d-norgestrel, and Group III received 50 μg ethinylestradiol plus a high dose of 500 μg d-norgestrel. Groups I and II had significantly elevated total plasma cholesterol and LDL-C compared to controls. In Group II total plasma LPL activator property was significantly lower (65.0 ± 18.4 u/ml; mean ± SD) than controls (78.1 ± 21.4 u/ml) Group II also had significantly higher total plasma triglycerides (145.8 ± 51.7 mg/dl) compared to controls (96.8 ± 21.8 mg/dl). Compared to Group II, women in Group III had significantly lower total plasma triglycerides (113.1 ± 48.8 mg/dl) and higher LPL activating property (82.1 ± 22.1 u/ml) than women in Group II.These data extend previous reports on the effects of oral contraceptives on plasma lipids and lipoproteins and suggest that sex steroids may affect plasma triglycerides by influencing apolipoproteins that modulate lipoprotein lipase activity.     

Haemostatic alterations in malaria correlate to parasitaemia

Fibrin(ogen) degradation products, platelet counts, antithrombin III, and the components of the Factor VIII complex were studied in a total of 80 patients with Plasmodium falciparum, Plasmodium vivax or Plasmodium ovale infections. The haemostatic findings were correlated to the numbers of parasitized erythrocytes and to each other. The results indicate that haemostatic changes in malaria correlate with the degree of parasitaemia. Evidence for moderate hyperfibrinolysis was found in patients with high P. falciparum parasitaemias only. Thrombocytopenia closely corresponded to parasitaemia and to von Willebrand factor levels, but appeared not to be linked to a consumption of coagulation factors. It was concluded that thrombocytopenia in malaria is not indicative of disseminated intravascular coagulation (DIC) but may relate to endothelial damage.     

Impact of long-term hormone replacement therapy on in vivo and in vitro markers of lipid oxidation

Postmenopausal hormone replacement therapy (HRT) with estrogen has been suggested to inhibit oxidation of low-density lipoprotein (LDL) in vitro, but progestins may oppose this effect. We studied whether estrogen HRT and combined HRT with estrogen and progestin differ in their ability to resist in vivo and in vitro oxidation of lipids. Study group included 15 women on oestradiol valerate (mean age 56 years, treatment duration 10.5 years) and 15 women on combined HRT with oestradiol valerate and levonorgestrel (mean age 58 years, treatment duration 11.3 years). In addition to lipid and apolipoprotein concentrations, the lagtime of LDL to oxidation, the rate of the propagation phase and the maximum concentration of conjugated dienes were recorded as indices of LDL susceptibility to copper-induced oxidation in vitro. As an in vivo marker of oxidative stress we measured 24-h excretion of urinary 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha). All measurements were done after long-term HRT (baseline), after 4 weeks pause and again 3 weeks after reintroduction of HRT. High-density lipoprotein (HDL) cholesterol and apolipoprotein AI concentrations were significantly higher and LDL to HDL ratio significantly lower after long-term oestradiol valerate therapy than after combined therapy. Simultaneously, the triglyceride and lipoprotein (a) levels were higher in the estrogen group. Susceptibility of LDL to oxidation and the level of 8-iso-PGF2alpha were similar in both groups at all measurement points, and treatment group was not a statistically significant determinant of these markers at baseline. According to these results, estrogen and combined HRT do not differ in their abilities to oppose LDL oxidation in vitro or systemic oxidative stress in vivo, but have differential effects on blood lipids.     

Increase of Classic and Nonclassic Cardiovascular Risk Factors in Patients with Acromegaly

ObjectiveTo evaluate the prevalence of classic and nonclassic cardiovascular risk factors in patients with acromegaly.MethodsSixty-two patients with acromegaly (50 with active disease and 12 with controlled acromegaly) and 36 healthy persons (the control group) underwent measurement of lipids, fasting plasma glucose, homeostasis model assessment of insulin resistance (HOMA-IR) index, Lp(a), high-sensitivity C-reactive protein (hsCRP), homocysteine, and variables primarily related to thrombogenesis (fibrinogen, antithrombin III, protein C, and protein S).ResultsIn comparison with control subjects, patients with active acromegaly had significantly higher mean values of fasting plasma glucose, total cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein (VLDL) cholesterol, triglycerides, Lp(a), HOMA-IR, and fibrinogen as well as lower mean levels of high-density lipoprotein cholesterol and protein S. In both groups, homocysteine, antithrombin III, protein C, and hsCRP levels were similar. Moreover, patients with active acromegaly, in comparison with those who had controlled acromegaly, presented with significantly higher values of fasting plasma glucose, HOMA-IR, triglycerides, VLDL cholesterol, Lp(a), and fibrinogen, whereas hsCRP and protein S were significantly lower. Finally, low levels of high-density lipoprotein cholesterol and protein S as well as elevated values of VLDL cholesterol, triglycerides, HOMA-IR, and fasting plasma glucose were more prevalent in patients with active acromegaly than in the other groups.ConclusionOur findings demonstrate that, in comparison with control subjects and patients with controlled acromegaly, patients with active acromegaly had a higher frequency of classic and nonclassic cardiovascular risk factors. These findings are potentially very important because acromegaly is associated with a 2- to 3-fold increase in mortality rate, predominantly related to cardiovascular disease. (Endocr Pract. 2007;13:363-372)     

Age-related changes in blood coagulation and fibrinolysis in mice fed on a high-cholesterol diet.

To investigate the pathogenesis of hyperlipidemia-induced atherosclerosis, we examined age-dependent changes in platelet activity, blood coagulation and fibrinolysis in susceptibility to a high cholesterol diet (HCD) feeding in male ICR mice. Pretreatment of platelet-rich-plasma from HCD feeding mice for 3 days with epinephrine (300 microM) resulted in a marked enhancement of adenosine 5'-diphosphate (ADP: 0.1 microM) or collagen (0.7 microgram/ml)-stimulated aggregation compared with the same in control mice. Yohimbine as alpha 2-adrenergic blocker antagonized these aggregations in a dose-dependent manner. A significant increase in plasma total cholesterol and VLDL (very low-density lipoprotein)-LDL (low-density lipoprotein)-cholesterol and the liver/body weight ratio was observed in mice fed on HCD for 3 months (3-month HCD mice). In the early phase of this experiment, a significant increase in fibrinogen was observed. In the middle phase, increases in the activity of antithrombin III (ATIII) and alpha 2-plasmin inhibitor (alpha 2-Pl) followed. Plasminogen content gradually decreased in both normal diet and HCD mice throughout the experiment. The activity of plasminogen activator inhibitor (PAI) decreased in 3-month HCD mice. Morphological observation of the aortic arch from 3-month HCD mice revealed apparent atheromatous plaques not seen in control mice. These results suggest that 3-month HCD mice can be a convenient hyperlipidemia-induced atherosclerotic model and the changes in platelet activity, coagulation and fibrinolysis in the early phase may be a cause of pathologic changes in this model.     

Maternal malaria induces a procoagulant and antifibrinolytic state that is embryotoxic but responsive to anticoagulant therapy

Low birth weight and fetal loss are commonly attributed to malaria in endemic areas, but the cellular and molecular mechanisms that underlie these poor birth outcomes are incompletely understood. Increasing evidence suggests that dysregulated hemostasis is important in malaria pathogenesis, but its role in placental malaria (PM), characterized by intervillous sequestration of Plasmodium falciparum, proinflammatory responses, and excessive fibrin deposition is not known. To address this question, markers of coagulation and fibrinolysis were assessed in placentae from malaria-exposed primigravid women. PM was associated with significantly elevated placental monocyte and proinflammatory marker levels, enhanced perivillous fibrin deposition, and increased markers of activated coagulation and suppressed fibrinolysis in placental plasma. Submicroscopic PM was not proinflammatory but tended to be procoagulant and antifibrinolytic. Birth weight trended downward in association with placental parasitemia and high fibrin score. To directly assess the importance of coagulation in malaria-induced compromise of pregnancy, Plasmodium chabaudi AS-infected pregnant C57BL/6 mice were treated with the anticoagulant, low molecular weight heparin. Treatment rescued pregnancy at midgestation, with substantially decreased rates of active abortion and reduced placental and embryonic hemorrhage and necrosis relative to untreated animals. Together, the results suggest that dysregulated hemostasis may represent a novel therapeutic target in malaria-compromised pregnancies.