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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors summarize the role of the vascular endothelium in hemostasis, thrombosis, vasomotor regulation, inflammation and angiogenesis. Quiescent endothelium is antithrombogenic, whereas perturbed endothelial cells become thrombogenic. The endothelium produces both vasodilating substances like endothelial derived relaxing factor and prostacyclin and vasoconstrictive compounds such as the endothelins. The presence of leucocyte adhesion molecules on the endothelial surface allows specific interactions with circulating leucocytes. Surface expression of HLA-antigens class I and II further underscores the importance of the endothelial cells in the inflammatory process. In the recent years it has become evident that the endothelial cells play a major role in the pathogenesis of diseases such as atherosclerosis, preeclampsia, hemolytic uremic syndrome and certain vasculitides.
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PMID:[The vascular endothelium--a multifunctional organ]. 155 34

The beneficial effects of combined estrogen-progestin-containing oral contraceptives (OCs) include prevention of pregnancy (less than 1 failure out of 100 regular users); the prevention of ectopic pregnancy; the reduction of preeclampsia (2.4 times lower risk compared with barrier methods); and reduction of pelvic inflammation to about one-half. The effects on menstruation include the reduction of sideropenic anemia (by lowering the incidence and duration of menstruation, OCs reduce the loss of iron to 50% or to as much as 33%); dysmenorrhea by 40% (symptoms receded in 90% of users); and premenstrual syndrome by 30%. OCs exert a favorable effect on menstrual epilepsy; reduce sports-related accidents in the premenstrual and menstrual periods; and reduce intermenstrual bleeding. The protection from cancer includes the lowering of endometrial cancer risk (every 2 years of use reduces the risk by 38%, 12 years of use by 70%, and the beneficial effects last 3-15 years); reduction of the risk of the ovarian cancer (already 3-6 months of use reduces the risk by 30%, and more than 5 years by 50% in women under 50 years of age with a longterm effect of 10 years or more, which drops sharply in women over 60 who are mostly at risk). Among other beneficial effects, they reduce benign mastopathy by 50-75%; reduce the risk of follicular ovarian cysts to 50% and the risk of corpus luteal ovarian cysts to 1/5; and they lessen bone loss which favorably affects osteoporosis. Low-dose OCs minimize the well-known risks of thrombotic and cerebrovascular accidents, myocardial infarction, hypertension, altered carbohydrate metabolism, gallbladder diseases, and liver cancer. A new OC with 30 mcg of ethinyl estradiol was tested with daily doses of 150 mcg of desogestrel. The high density lipoprotein (HDL) either increased or did not change with desogestrel: the HDL2 subfraction that protects from atherosclerosis did not change, and probably the HDL3 raised the HDL level.
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PMID:[Favorable effects of oral estrogen-progestin contraception]. 181 41

Genetic influences in cerebrovascular disease (CVD) may act either independently or by predisposing to, or modulating, the effect of risk factors such as hypertension. Factors involved in the pathogenesis of atherosclerosis, thrombosis and vasoconstriction are important in CVD. The angiotensinogen gene has recently been linked with essential hypertension in affected sibships and a particular polymorphism in exon 2 of the angiotensinogen gene, a threonine to methionine substitution at position 235 (M235T), has been associated with pre-eclampsia and hypertension. In this study we examined the relation of M235T polymorphism to cerebrovascular disease and carotid atheroma in 100 consecutive Caucasian patients with internal carotid artery territory ischaemia (TIA or stroke), presenting to a carotid ultrasound service. Forty five age-matched controls (mostly patients' spouses) were also studied. Hypertension was defined as current treatment with anti-hypertensive agents, or SBP > 160 mm Hg or DBP > 95 mm Hg. Twelve of 100 cases (12%) and eight of 45 controls (12%) were homozygous for the T235 allele. T:M allele ratios were 0.34:0.66 in cases and 0.34:0.66 in controls. There was no relation between the polymorphism and either internal carotid stenosis or common carotid artery intima-media thickness. In the cases, mean percentage internal carotid artery stenosis was TT 18.3 (SD 18.7)%, MT 38.0 (27.1)% and MM 36.8 (30.2)%. Mean intima-media thickness was TT 0.87 (0.18) mm, MT 0.95 (0.34) mm and MM 0.88 (0.23) mm. There was no relation between the polymorphism and hypertension (TT 11 of 100 cases, six of 45 controls).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lack of association between angiotensinogen polymorphism (M235T) and cerebrovascular disease and carotid atheroma. 852 90

Several years ago the hypothesis was advanced that alterations of endothelial function could explain much of the pathophysiology of preeclampsia. Since that time, extensive data have been generated to support the hypothesis. Markers of endothelial activation can be demonstrated in women with overt preeclampsia. More importantly, many of these markers precede clinically evident disease and disappear with resolution of the disease. The original postulate was that materials produced by the poorly perfused placenta, which is characteristic of preeclampsia, entered the systemic circulation and altered endothelial cell activity. This was proposed to change vascular sensitivity to circulating pressors, activate coagulation, and reduce vascular integrity resulting in the pathophysiological changes of preeclampsia. As data have accumulated it has become increasingly evident that the insult to the endothelium is neither toxicity nor nonspecific injury but rather can better be characterized as endothelial activation. Candidate molecules have been suggested but not established. It seems likely that the responsible agent(s) will not be unique molecules but rather usual molecules present in excessive amounts. The hypothesis has been expanded to invoke involvement of the maternal constitution in the generation of endothelial injury and injurants. This concept is stimulated by the observation that reduced placental perfusion per se is not sufficient to generate the maternal syndrome. Women with growth-restricted fetuses frequently are not preeclamptic. Placental bed biopsies from not only growth-restricted but also prematurely born infants demonstrate failure of the physiological remodeling of decidual vessels responsible for the reduced placental perfusion of preeclampsia. This has led to the concept that preeclampsia is secondary to an interaction of reduced placental perfusion and maternal factors. Interestingly these maternal factors, obesity, insulin resistance, black race, hypertension, and elevated plasma homocysteine concentration are all risk factors for atherosclerosis in later life.
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PMID:Endothelial dysfunction in preeclampsia. 965 3

The dominating hypothesis of the preeclampsia syndrome (PES) is that placentally derived factors are released to the maternal circulation. These factors are believed to alter endothelial properties resulting in disturbed vasomotor function, increased endothelial permeability, and activation of thrombogenic factors. However, the impact of placentally derived factors on the endothelial cells is influenced by another major variable: the "sensitivity" of the maternal endothelium to the placental factors. Several maternal factors may play a role in determining this sensitivity. They include chronic hypertension, diabetes, and hyperlipidemia. In this article we discuss the possible role of hyperlipidemia (especially high free fatty acids and hypertriglyceridemia) in the pathogenesis of preeclampsia, viewed from this perspective. Pregnancy in general, preeclamptic pregnancy in particular, is associated with a marked hyperlipidemia. We suggest a parallel to atherosclerotic diseases, wherein hyperlipidemia induces endothelial dysfunction, probably by promoting oxidative stress in the arterial wall. The hyperlipidemia of pregnancy may have a similar effect on the endothelial cells. When placentally derived endothelial disturbing factors, like lipid peroxides and trophoblastic components, are released into the maternal circulation, their effects on the endothelium may be enhanced because of hyperlipidemia-mediated activation or "sensitization" of the endothelial cells. Alternatively, placentally derived factors like peroxides may combine with lipoproteins, forming complexes that are more disturbing to cells than the placental factors or lipoproteins are individually. We also discuss the possible role of maternal hyperlipidemia in aggravating placental insufficiency caused by poorly transformed spiral arteries. The hemodynamic flow pattern may be markedly different in completely and incompletely transformed spiral arteries. By analogy to the fundamental role of hemodynamic factors in development of atherosclerosis, we pose the hypothesis that abnormally transformed spiral arteries have an "atherogenic" blood flow pattern that promotes lipid deposition and "acute atherosis".
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PMID:Plasma lipids and vascular dysfunction in preeclampsia. 965 5

There are two distinct histological manifestations of impaired placental implantation in humans--incomplete trophoblastic vascular invasion and atherosis. Both have been described to occur in pregnancies affected by a variety of disorders such as preeclampsia, fetal growth restriction, systemic lupus erythematosus, and diabetes. Our purpose was to integrate recent developments in the understanding of implantation site disorders into a pathophysiological scenario that interrelates these placentation disorders and associated pregnancy complications. Sources were identified from a MEDLINE search of English-language articles published from 1966 to 1997. Additional sources were identified from references cited in relevant reports. We selected articles relating to the following topics: atherosis, implantation site disorders, trophoblastic invasion, preeclampsia, fetal growth restriction, implantation site development, atherosclerosis, and endothelial activation-damage. A contemporary version of normal placentation, including vascular adaptation, was reviewed with comments on normal trophoblastic differentiation and vascular invasion. Specific abnormalities of the implantation site, including atherosis and incomplete trophoblastic invasion, were discussed in the context of placental site hypoperfusion and the association with pregnancy complications. It was concluded that atherosis and incomplete trophoblastic invasion may be both a consequence and a cause of placental site hypoperfusion resulting in the development of preeclampsia and a variety of other pregnancy disorders.
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PMID:Atherosis revisited: current concepts on the pathophysiology of implantation site disorders. 1007 38

Obstetrical problems sometimes portend manifestations of atherosclerosis, as illustrated by two case reports. The first patient had the combination of hyperhomocysteinaemia due to chronic vitamin deficiencies in the diet, and smoking. The second was also a smoker and had a genetically determined mild hyperhomocysteinaemia, aggravated by chronic vitamin deficiencies resulting from poor dietary habits; she also had an increased folic acid requirement because of use of anti-epileptic drugs in combination with a familial predisposition for premature atherosclerotic manifestations. The first patient had four pregnancies, two of which ended in intrauterine foetal death due to placental infarction, and one in the birth of a dysmature boy. The second patient's four pregnancies ended twice in abortion and twice in the birth of a dysmature child; in one of the latter cases placental infarction was observed. Both women subsequently suffered cerebrovascular accidents while in addition, older cerebral infarctions were found to be present. Women with recurrent abortion, pre-eclampsia, placental infarction, placental detachment and foetal growth retardation should be examined, even if other risk factors are also present, for (mild) hyperhomocysteinaemia, and treated for it with vitamin suppletion (folic acid, vitamins B6 and B12), even although admittedly more research is necessary to make certain that such treatment has a preventive effect on the manifestations of this disorder.
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PMID:[Obstetric problems followed by stroke]. 1034 22

In recent years it has become apparent that the oxidation of lipids, or lipid peroxidation, is a crucial step in the pathogenesis of several disease states in adult and infant patients. Lipid peroxidation is a process generated naturally in small amounts in the body, mainly by the effect of several reactive oxygen species (hydroxyl radical, hydrogen peroxide etc.). It can also be generated by the action of several phagocytes. These reactive oxygen species readily attack the polyunsaturated fatty acids of the fatty acid membrane, initiating a self-propagating chain reaction. The destruction of membrane lipids and the end-products of such lipid peroxidation reactions are especially dangerous for the viability of cells, even tissues. Enzymatic (catalase, superoxide dismutasse) and nonenzymatic (vitamins A and E) natural antioxidant defence mechanisms exist; however, these mechanisms may be overcome, causing lipid peroxidation to take place. Since lipid peroxidation is a self-propagating chain-reaction, the initial oxidation of only a few lipid molecules can result in significant tissue damage. Despite extensive research in the field of lipid peroxidation it has not yet been precisely determined if it is the cause or an effect of several pathological conditions. Lipid peroxidation has been implicated in disease states such as atherosclerosis, IBD, ROP, BPD, asthma, Parkinson's disease, kidney damage, preeclampsia and others.
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PMID:Lipid peroxidation and tissue damage. 1045 7

Normal pregnancy is a physiological condition of balanced hypercoagulability. However, in preeclamptic pregnancies, the coagulation and fibrinolytic cascades are highly activated, accompanied by pathological blood rheology and endothelial dysfunction. This may result in disseminated intravascular coagulation (DIC). Atherosclerosis research showed that lipids may interfere with coagulation and cause endothelial dysfunction. Therefore, we analyzed the lipoprotein distribution and platelet counts in uncomplicated preeclamptic and HELLP syndrome pregnancies. In addition, a correlation between the fetal circulation determined by Doppler velocimetry and the maternal lipid metabolism was investigated. Fasting serum was collected from 24 women in the third trimester of uncomplicated pregnancies, 9 women with severe preeclampsia, and 6 women with HELLP syndrome. Cholesterol (CH), triglycerides (TGs), and apolipoproteins were analyzed in serum and in very-low-density (VLDL), intermediate-density (IDL), low-density (LDL), and high-density (HDL) lipoproteins separated by ultra-centrifugation. Compared with normal pregnancies, TGs in serum, VLDL, IDL, LDL, and HDL were significantly increased in preeclampsia; no difference in CH concentrations was observed. During HELLP syndrome, IDL-TGs were increased compared with normal pregnancies. There was no clear correlation between fetal hemodynamics and maternal lipid metabolism, but there was a significant negative correlation between maternal platelet counts and serum TG levels. Because TG-rich particles may play an important role in thrombin generation and may induce platelet aggregation, the observed changes in lipoprotein metabolism in preeclampsia and HELLP syndrome may contribute to the coagulopathy seen in these conditions.
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PMID:Altered lipid metabolism in preeclampsia and HELLP syndrome: links to enhanced platelet reactivity and fetal growth. 1062 2

Lipoprotein (a) (Lp(a)) is recognised as a risk factor for arterial and venous thrombosis, a property which may relate to its structural similarity to plasminogen. Pregnancy is associated with a hypofibrinolytic state. Elevated Lp(a) may influence fibrinolysis and have an unfavourable role in pregnancy outcome. In this study alterations in plasma Lp(a) concentrations during normal pregnancy was examined, in a detailed longitudinal investigation, in ten women together with changes in other lipid parameters. In addition, Lp(a) concentrations were examined in subjects with pre-eclampsia (n=10) relative to matched controls (n=10), since it has recently been reported that a substantial increase in circulating Lp(a) occurs in this disorder. Lp(a) concentration increased steadily in normal pregnancy between 10 and 35 weeks with a doubling of the median value from 14.5 to 27.0 mg/dl (P=0.01). A significant increase in Lp(a) values was observed in all subjects with increasing gestation (median rise 190%, range 117-340%). This increase was intermediate to those seen in plasma triglyceride and cholesterol. No significant difference in Lp(a) values was observed in subjects with pre-eclampsia, compared with matched normal pregnancy controls (median 14 mg/dl [IQR 4.7-69.0] in pre-eclampsia vs 20 mg/dl [9.0-56. 3] in controls; P=0.57), at a median gestation of 32 weeks. In conclusion, there is a 2-fold increase in Lp(a) during normal pregnancy, which may influence fibrinolysis. Circulating Lp(a) is not significantly elevated in women with pre-eclampsia, and thus is unlikely to play a role in the pathophysiology of this disorder.
Atherosclerosis 2000 Feb
PMID:Lipoprotein (a) levels in normal pregnancy and in pregnancy complicated with pre-eclampsia. 1065 77


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