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

Endothelin-1 is an endothelium-derived factor which alters tone and proliferation of vascular smooth muscle and has been implicated in the development of atherosclerosis. Estrogen modulates production of and contractile responses to endothelin-1. Since atherosclerosis is less in estrogen-replete women compared to men, experiments were designed to determine whether or not there were gender-associated differences in proliferative responses to endothelin-1 and effect of estrogen status on those responses. Proliferation of smooth muscle cells derived from coronary arteries of sexually mature, gondally intact male and female and oophorectomized female pigs was determined by thymidine incorporation in the absence and presence of endothelin-1 with and without 17beta-estradiol. Endothelin-1 (10(-9) M to 10(-7) M) significantly inhibited proliferation only in coronary smooth muscle cells from intact female pigs. Addition of beta-estradiol inhibited proliferation of cells from intact females but there was not a synergistic effect with endothelin-1. Gender associated inhibition of smooth muscle proliferation by endothelin-1 may contribute, in part, to cardioprotection noted in estrogen-replete states.
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PMID:Gender-related differences in proliferative responses of vascular smooth muscle cells to endothelin-1. 1157 75

Most epidemiological studies have suggested that the administration of estrogen reduces cardiovascular risk in healthy postmenopausal women. More recently, however, in the large Heart Estrogen/progestin Replacement Study (HERS), it was unexpectedly found that in women with established cardiovascular disease, there was overall no difference in cardiovascular events between those treated with combined oestrogen/progestin hormone replacement therapy and those on placebo. The aim of this study was to examine the effect of combined hormone replacement therapy on arterial reactivity in women with existing angina pectoris. Seventy-four postmenopausal women with angina pectoris were recruited into a 16 week double-blind, placebo-controlled study of treatment with 2 mg of estradiol combined with 1 mg of norethisterone acetate daily. The median endothelium-dependent change in arterial relaxation increased from 5.00 to 7.69% in the treatment group and decreased from 5.57 to 3.64% in the controls. The median endothelium-independent change in arterial relaxation increased from 6.49 to 7.27% in the treatment group and decreased from 4.39 to 2.07% in the controls. The changes in arterial relaxation between the treatment and control groups were not statistically significant. The administration of estrogen/progestin did not significantly improve either endothelium-dependent or -independent arterial relaxation in postmenopausal women with established cardiovascular disease. We have previously shown that estrogen/progestin treatment improves endothelium dependent relaxation in healthy women. The results of our study provide one possible explanation for the clinical findings of the HERS study. In women with established cardiovascular disease, arterial relaxation does not increase significantly in response to treatment with combined hormone replacement therapy.
Atherosclerosis 2001 Dec
PMID:The effect of continuous combined hormone replacement therapy on arterial reactivity in postmenopausal women with established angina pectoris. 1173 Aug 28

An impressive body of evidence has suggested that estrogen therapy should be helpful to slow the pathogenesis or progression of atherosclerosis. Estrogen's favorable effects on lipids and endothelial function, coupled with extensive observational epidemiology and data from animal models of atherosclerosis, persuaded many that hormone replacement therapy (HRT) would be helpful for both primary and secondary prevention of coronary disease. Recently, several randomized clinical trials of HRT have been completed, and several more are currently under way. These trials include both primary and secondary prevention cohorts and use clinical as well as anatomic manifestations of atherosclerosis as outcomes. These trials are producing surprising and controversial results that will radically alter contemporary understanding of the role of HRT for cardiovascular disease prevention. This review briefly describes the findings of the Heart and Estrogen/Progestin Replacement Study, the Estrogen Replacement and Atherosclerosis Trial, and other recently completed clinical trials. Trials that are under way are also described and discussed.
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PMID:Cardiovascular trials of estrogen replacement therapy. 1179 47

Epidemiological observations, clinical mechanistic studies, and basic laboratory research suggest that estrogen therapy is associated with beneficial cardiovascular effects in postmenopausal women. Estrogen has a multitude of biological effects that may account for this apparent benefit (which remains to be proved in randomized clinical trials), including favorable effects on the lipid profile, increased endothelial nitric oxide bioactivity, and enhanced fibrinolysis. However, long-term estrogen therapy increases the risk of breast and endometrial cancers. Raloxifene, a benzothiophene derivative that binds to the estrogen receptor, is a selective estrogen receptor modulator, producing estrogen-agonist effects in some tissues (liver, bone) and estrogen-antagonistic effects in others (breast, uterus), and may prove to be an option for women with atherosclerosis or its risk factors. This review updates the current knowledge of the biological effects of selective estrogen receptor modulators of potential cardiovascular importance in postmenopausal women.
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PMID:Selective estrogen receptor modulator effects on serum lipoproteins and vascular function in postmenopausal women and in hypercholesterolemic men. 1179 50

There is strong evidence from both human and nonhuman primate studies supporting the conclusion that estrogen deficiency increases the progression of atherosclerosis. More controversial is the conclusion that postmenopausal estrogen replacement inhibits the progression of atherosclerosis. Estrogen treatment of older women (>65 years) with pre-existing coronary artery atherosclerosis had no beneficial effects. In contrast, estrogen treatment of younger postmenopausal women or monkeys in the early stages of atherosclerosis progression has marked beneficial effects. Whether progestogens attenuate the cardiovascular benefits of estrogen replacement therapy has been controversial for more than a decade. Current evidence from studies of both monkeys and women suggest little or no attenuation of estrogen benefits for coronary artery atherosclerosis. Lack of compliance with estrogen replacement therapy, usually because of fear of breast cancer, remains a major problem. Future regimens may overcome that fear by the co-administration of a breast cancer preventive agent (i.e., selective estrogen receptor modulators, phytoestrogens) with low dose estrogen.
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PMID:Estrogen replacement therapy, atherosclerosis, and vascular function. 1186 Oct 31

Estrogen receptors (ESR) 1 and 2 are expressed in the normal and atherosclerotic arteries mediating the atheroprotective action of estrogen to artery wall cells. Whether variants of these receptor genes associate with autopsy-verified coronary artery wall atherosclerosis is not known. This study investigated whether variants of the ESR1 gene are associated with autopsy-verified coronary artery wall atherosclerosis and thrombosis. Coronary arteries were taken from 300 white Finnish male autopsy cases aged 33-69 years included in the Helsinki Sudden Death Study. Areas of coronary wall covered with fatty streaks, fibrotic, calcified, and complicated lesions were measured using computer-assisted planimetry and related to ESR1 PvuII genotypes (P/P, P/p, and p/p) determined by PCR. The mean area of complicated lesions of three major coronaries and the presence of coronary thrombosis were significantly associated with the ESR1 genotype in men aged 53 years or older (median age as a cut off point). No such association was found in men aged under 53 years. After adjusting for age and body mass index the men aged 53 years or over with P/p and P/P genotype had areas of complicated lesions on average two- and fivefold larger than subjects with the p/p genotype. The age and body mass index adjusted odds ratios for coronary thrombosis were 6.2 for P/p and 10.6 for P/P compared to men with the p/p genotype. After additional adjustment for diabetes and hypertension the ESR1 genotype persisted as an independent predictor of complicated lesions ( P=0.007) and coronary thrombosis. In conclusion, the ESR1 gene is a potential candidate behind the pathogenesis of acute coronary events.
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PMID:Coronary artery wall atherosclerosis in relation to the estrogen receptor 1 gene polymorphism: an autopsy study. 1189 38

1. The rationale for preclinical research on the atheroprotective effect of oestrogens is based on the epidemiological evidence that women are protected against the clinical complications of atherosclerosis until menopause. However, this protection, probably due to sex hormones, is progressively lost within the years following menopause. 2. In addition, numerous studies have clearly demonstrated the atheroprotective effect of oestrogens in all animal models. 3. In the present paper, we first summarize our understanding of the pathophysiology of atherosclerosis. We then focus on the recognized target of oestradiol (E2) in the vessel wall: the classical target, namely the endothelium, and a recently characterized target, namely cells of the inflammatory-immune system. Finally, we discuss how unknown mechanisms in atherosclerosis could be responsible for the absence of effect of hormone-replacement therapy in the Heart and Estrogen/ progestin Replacement Study (HERS).
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PMID:Vasculoprotective effects of oestrogens. 1190 9

Clearly, a new era has begun, with increasing numbers of the scientific/medical community asking whether estrogens have any cardiovascular benefits. Doubts have arisen from two randomized prospective trials. The Heart and Estrogen/progestin Replacement Study (women who were generally beyond 65 years of age with preexisting coronary heart disease) found no benefit in reducing coronary events by a combination of estrogens and a progestin. Later, the Estrogen Replacement Atherosclerosis Trial reported that no benefit could be shown for either conjugated equine estrogens only or the combined therapy group for women with preexisting coronary artery stenosis. There are lessons to be taken from monkey models about the new conundrum. Estrogens have beneficial effects in the early stages of atherogenesis, but have little or no beneficial effects in the final stages of plaque complications, instability and coronary heart disease events. Using the monkey model, we have addressed the question of when "primary prevention" should begin. We examined the effect of contraceptive steroid treatment of stressed animals at high risk to progressing atherosclerosis due to their estrogen deficiency and subsequently examined the effect of estrogen replacement therapy or no estrogen replacement therapy following surgical menopause. The most robust inhibition of atherosclerosis progression was found in those animals given contraceptive steroids premenopausally and subsequently estrogen replacement postmenopausally. The notion of starting contraceptive therapy during the perimenopausal period to be followed immediately with estrogen replacement postmenopausally is likely to be the most favorable approach to the inhibition of atherosclerosis progression.
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PMID:The new conundrum: do estrogens have any cardiovascular benefits? 1199 32

Numerous observational studies have previously shown that estrogen therapy (ERT) or estrogen/progestin hormone replacement therapy (HRT) can significantly reduce the risk of Coronary Artery Disease (CAD) in healthy postmenopausal women by up to 50%. However, due to statistical limitations inherent in these earlier studies, several large randomised trials are now under way. The results from some of these randomised trials are expected sometime in 2005 and will certainly help confirm or refute the present perceived cardio-protective effects of ERT/HRT in healthy menopausal women. On the other hand, the role of hormonal therapy in menopausal women with established CAD is more controversial. Although results from earlier observational trials have been encouraging, more recent randomised controlled data from the Heart and Estrogen/Progestin Replacement (HER) study and the Estrogen Replacement and Atherosclerosis (ERA) study have been more sober. In fact, both have generally reported on the failure of ERT/HRT to reduce the overall rate of ischaemic cardiovascular events or to halt the progression of coronary atherosclerosis in menopausal women with established CAD. However, these studies are not without their own limitations. As such, more future trials will be needed before the role of postmenopausal hormone therapy in the secondary prevention of CAD can be firmly established.
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PMID:Hormone replacement therapy (HRT) and ischaemic heart disease: getting to the heart of the matter. 1200 77

Blood vessel cells express the 2 known estrogen receptors, alpha and beta (ERalpha, ERbeta), which are thought to mediate estrogen inhibition of vascular injury and atherosclerosis, but the relative role of ERalpha and ERbeta in these events is controversial. Estrogen inhibits the vascular injury response to the same extent in ovariectomized female wild-type mice and in the original single gene knockout mice for ERalpha (ERalphaKO(Chapel Hill) [ERalphaKO(CH)]) and ERbeta (ERbetaKO(Chapel Hill) [ERbetaKO(CH)]). In double gene knockout mice generated by crossing these animals (ERalpha,betaKO(CH)), estrogen no longer inhibits medial thickening after vascular injury, but still inhibits vascular smooth muscle cell proliferation and increases uterine weight. The partial retention of estrogen responsiveness in ERalpha,betaKO(CH) mice could be due either to the presence of a novel, unidentified estrogen receptor or to functional expression of an estrogen receptor-alpha splice variant in the parental ERalphaKO(CH) mice. To distinguish between these possibilities, we studied recently generated mice fully null for estrogen receptor alpha (ERalphaKO(Strasbourg) [ERalphaKO(St)]) and examined the effect of estrogen on the response to vascular injury. In the present study, we show that after vascular injury in ovariectomized ERalphaKO(St) mice, estrogen has no detectable effect on any measure of vascular injury, including medial area, proteoglycan deposition, or smooth muscle cell proliferation. These data demonstrate that estrogen receptor-alpha mediates the protective effects of estrogen on the response to vascular injury.
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PMID:Estrogen receptor-alpha mediates the protective effects of estrogen against vascular injury. 1203 98


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