Does hormone replacement therapy inhibit coronary artery calcification?

Shemesh, Joseph; Frenkel, Yair; Leibovitch, L; Grossman, Ehud; Pines, Amos; Motro, Michael

doi:10.1016/s0029-7844(97)00143-9

Cited by 26 publications

(13 citation statements)

References 20 publications

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“…Another important observation is that the ability of both 17␤-estradiol and raloxifene to alter the phenotype of VSMCs is dependent on the hormonal status of the animals from which cells were derived. These results have important implications toward understanding how hormone therapy could reduce arterial calcification postmenopause (52).…”

Section: Discussionmentioning

confidence: 87%

“…The idea that osteoblast-specific genes could link osteoporosis and arterial calcification is supported indirectly by the high clinical prevalence of arterial calcification and cardiovascular disease in postmenopausal women with osteoporosis (19,27,48). An estrogen-replete condition correlated with decreased incidence of coronary arterial calcification in women (12,52). However, it is not known whether reduced arterial calcification results from effects of estrogen on bone-like characteristics within populations of VSMCs (3,18).…”

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confidence: 99%

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Differential effects of 17β-estradiol and raloxifene on VSMC phenotype and expression of osteoblast-associated proteins

Rzewuska-Lech¹,

Jayachandran²,

Fitzpatrick³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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Rzewuska-Lech, Ewa, Muthuvel Jayachandran, Lorraine A. Fitzpatrick, and Virginia M. Miller. Differential effects of 17␤-estradiol and raloxifene on VSMC phenotype and expression of osteoblast-associated proteins. Am J Physiol Endocrinol Metab 289: E105-E112, 2005. First published February 15, 2005 doi:10.1152/ajpendo.00366.2004.-Several studies demonstrate an association between osteoporosis and arterial calcific disease, both of which being common in elderly women. Estradiol and raloxifene, a selective estrogen receptor modulator, prevent bone loss in postmenopausal women. Little is known regarding how these agents affect arterial calcification. The aim of this study was to determine whether or not 17␤-estradiol and raloxifene reduced vascular smooth muscle cell (VSMC) differentiation and expression of bone-associated proteins during phosphate-induced calcification in vitro. Aortic VSMC were cultured from adult, gonadally intact, and ovariectomized (OVX) female pigs. Calcifying medium was added, and cells were treated with solvent (control), 17␤-estradiol (E2), or raloxifene. Extent of calcification and phenotypic expression of bone-associated proteins [matrix gla protein (MGP), osteoprotegerin (OPG), and bone sialoprotein (BSP)] were examined at 3-day intervals over 2 wk. Calcium content increased in all groups but was greater in VSMC derived from intact compared with OVX animals. E 2 reduced calcification and preserved a contractile phenotype. Expression of OPG significantly decreased with time; this decrease was significantly greater in VSMC derived from OVX compared with gonadally intact pigs. E 2 and raloxifene preserved expression of OPG only in VSMC from intact pigs. Expression of MGP increased significantly with time and was not affected by E 2 or raloxifene treatments. E2 treatment significantly inhibited synthesis of BSP in cells from both groups. In conclusion, E2 slows differentiation of VSMC induced by excess phosphate. Effectiveness of raloxifene to preserve expression of bone cell-associated proteins depends on the hormonal status of the tissue donor. vascular smooth muscle cells; estrogen; raloxifene; selective receptor modulator; smooth muscle phenotype

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Section: Discussionmentioning

confidence: 87%

mentioning

confidence: 99%

Differential effects of 17β-estradiol and raloxifene on VSMC phenotype and expression of osteoblast-associated proteins

Rzewuska-Lech¹,

Jayachandran²,

Fitzpatrick³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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“…However, this view was reversed once randomized controlled trials were performed in large numbers, pointing to the hazard of reliance on observational studies, 102,103 and opening the possibility that vascular calcification contributes to adverse effects. Some clinical studies now confirm higher calcium content in coronary plaques of women using hormone replacement therapy (HRT), 104,105 whereas other observational studies report reduction in coronary calcification with HRT. 106 Conclusions about the relationship between estrogen and coronary calcification cannot be reliably determined from observational studies.…”

Section: Menopausementioning

confidence: 99%

Vascular Calcification

Abedin

Tintut

Demer

2004

ATVB

786

220

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Abstract-Vascular calcification, long thought to result from passive degeneration, involves a complex, regulated process of biomineralization resembling osteogenesis. Evidence indicates that proteins controlling bone mineralization are also involved in the regulation of vascular calcification. Artery wall cells grown in culture are induced to become osteogenic by inflammatory and atherogenic stimuli. Furthermore, osteoclast-like cells are found in calcified atherosclerotic plaques, and active resorption of ectopic vascular calcification has been demonstrated. In general, soft tissue calcification arises in areas of chronic inflammation, possibly functioning as a barrier limiting the spread of the inflammatory stimulus. Atherosclerotic calcification may be one example of this process, in which oxidized lipids are the inflammatory stimulus. Calcification is widely used as a clinical indicator of atherosclerosis. It progresses nonlinearly with time, following a sigmoid-shaped curve. The relationship between calcification and clinical events likely relates to mechanical instability introduced by calcified plaque at its interface with softer, noncalcified plaque. In general, as calcification proceeds, interface surface area increases initially, but eventually decreases as plaques coalesce. Key Words: calcification Ⅲ atherosclerosis Ⅲ inflammation Ⅲ bone Ⅲ vascular V ascular calcification is an important manifestation of atherosclerosis. For more than half a century, it has been associated with a poor prognosis attributable to vascular disease. 1 Its presence is a strong indicator of chronic inflammatory disease, usually atherosclerosis, and its extent directly relates to the overall burden of atherosclerotic disease. 2 Despite its clinical relevance, research on the mechanism of mineral deposition in arteries has been limited and remains at an early scientific stage relative to research on other aspects of atherosclerosis, such as lipoprotein biochemistry and inflammation. Mechanisms of Vascular CalcificationVascular calcification recapitulates embryonic osteogenesis. Pathologists in the 19th century recognized the presence of bone-like tissue within atherosclerotic arteries, with lamellar structure, osteoblast-like cells, and hematopoietic elements. 3 Yet, for most of the 20th century, vascular calcification has been regarded as a passive, unregulated, degenerative process occurring within advanced atherosclerotic plaques. The concept of regulated ossification as the mechanism behind vascular calcification has re-emerged only in the past decade. 4,5 Ossification has been identified histologically in 60% of restenotic aortic valves after balloon valvuloplasty. 6 Approximately 15% of carotid atherosclerotic plaque specimens 7 and calcified cardiac valve tissue 8 have ossification. Vascular calcification may include both osteogenic and chondrogenic differentiation. In humans, it is primarily osteogenic with bone tissue formation, whereas in mice, it is primarily chondrogenic with cartilage formation. Although osteoblas...

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“…For example, in postmenopausal women arterial mineralization may serve as a marker for the extent of estrogen deficiency. 57 Finally, lesions in the extracranial carotid arteries may be related to cerebrovascular events either directly or primarily because they represent a measure of overall level of atherosclerosis. 12 Atherosclerosis, the same process we have imaged in the carotid arteries, is almost always the pathology underlying coronary heart disease, whereas various fibrotic and other arteriosclerotic processes affect the very small intracranial arteries and arterioles responsible for many of the stroke events.…”

Section: Hunt Et Al Carotid B-mode Acoustic Shadowing Predicts Strokementioning

confidence: 99%

Acoustic Shadowing on B-Mode Ultrasound of the Carotid Artery Predicts Ischemic Stroke

Hunt

Evans

Folsom

et al. 2001

Stroke

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Background and Purpose-We examined the relationship of carotid artery lesions (CALs), with and without acoustic shadowing (AS), to incident ischemic stroke events in the Atherosclerosis Risk in Communities study cohort. Methods-The study population consisted of 13 123 men and women aged 45 to 64 years, and free of stroke, examined during 1986 -1989. Over an average follow-up time of 8.0 years, 226 incident ischemic stroke cases (thromboembolic brain infarctions) were identified and classified by a standardized protocol. Three levels of exposure were defined on the basis of the presence of B-mode ultrasound-detected CALs and AS in a 3-cm segment of the carotid arteries centered at the bifurcation. Results-The hazard ratio for ischemic stroke adjusted for age, ethnicity, and study site for women with a CAL without AS, compared with those without a CAL, was 1.92 (95% CI, 1.23, 3.01), and the hazard ratio comparing those with a CAL with AS with those without a CAL was 4.01 (95% CI, 2.28, 7.06). The corresponding hazard ratios for men were 1.99 (95% CI, 1.36, 2.91) and 2.23 (95% CI, 1.32, 3.79). Although adjustment for diabetes, hypertension medication, systolic blood pressure, left ventricular hypertrophy score, fibrinogen, von Willebrand factor antigen, and smoking status attenuated these associations somewhat, when compared with no evidence of CALs, CALs with AS remained statistically significant predictors of ischemic stroke in women, while CALs without AS were predictive of ischemic stroke in men. Conclusions-B-mode ultrasound-detected CALs and AS serve as markers of atherosclerosis and thus are predictive of ischemic stroke.

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Does hormone replacement therapy inhibit coronary artery calcification?

Abstract: The lower incidence of coronary calcium in the HRT users suggests that HRT is associated with decreased prevalence of the coronary calcification.

Cited by 26 publications

References 20 publications

Differential effects of 17β-estradiol and raloxifene on VSMC phenotype and expression of osteoblast-associated proteins

Differential effects of 17β-estradiol and raloxifene on VSMC phenotype and expression of osteoblast-associated proteins

Vascular Calcification

Acoustic Shadowing on B-Mode Ultrasound of the Carotid Artery Predicts Ischemic Stroke

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