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

We have used the cynomolgus macaque as a model for the study of the effects of endogenous and exogenous sex steroid hormones on atherosclerosis and osteoporosis. As in human beings, premenopausal female cynomolgus macaques develop much less extensive coronary artery atherosclerosis than their male counterparts. Furthermore, surgical menopause results in a more atherogenic plasma lipoprotein pattern and an approximate doubling of atherosclerosis extent. Frequent pregnancy, a hyperoestrogenic state, results in an approximate 50% reduction in atherosclerosis extent. Physiological replacement with 17 beta-oestradiol alone or in combination with progesterone prevents the increase in coronary artery atherosclerosis extent associated with ovariectomy. This effect is independent of plasma lipoprotein concentrations and appears to be accounted for, at least in part, by an inhibitory effect of oestrogen replacement therapy on the uptake and degradation of LDL by the artery wall. Also, as in human beings, treatment with certain types of combination oral contraceptives results in marked decreases in plasma HDL-C concentration. Nonetheless, coronary artery atherosclerosis extent is reduced in monkeys by oral contraceptive treatment, and this effect is most pronounced among animals at highest risk due to theoretically adverse plasma lipoprotein profiles. It appears that, as with oestrogen replacement therapy, this effect can be accounted for, at least in part, by an inhibition of the uptake and degradation of low density lipoprotein by the artery wall. The monkey also appears to be a good model for studies of postmenopausal bone loss. As in women, surgical menopause results in significant diminution of bone mineral density and bone mineral content. Also, serum biomarkers of bone turnover (total alkaline phosphatase, acid phosphatase, tartrate-resistant acid phosphatase and osteocalcin) are increased in surgically postmenopausal monkeys, indicating increased bone turnover resulting from the surgical menopause. These increases in bone loss and indices of bone turnover were prevented by physiological oestrogen replacement therapy. Cynomolgus monkeys seem to be exceptionally useful models for studies of the effects of sex steroid hormones on atherosclerosis and osteoporosis, two major public health problems in postmenopausal women.
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PMID:Effects of oestrogens and progestogens on coronary atherosclerosis and osteoporosis of monkeys. 182 26

The influence of estrogen replacement therapy on bone loss of surgically postmenopausal cynomolgus macaques was evaluated histomorphometrically using the first (L-1) lumbar vertebra and ex vivo dual photon absorptiometry of the third (L-3) lumbar vertebra. The animals were a subgroup of a larger study on the effects of estrogen replacement therapy on diet-induced coronary artery atherosclerosis. The three experimental conditions were as follows: untreated females with oophorectomy, females with oophorectomy treated with continuous estrogen replacement therapy plus cyclic progesterone, and females with oophorectomy treated with estrogen replacement therapy. Bone mineral density (grams per square centimeter) of L-3, when covaried for body mass index (body mass index, body weight/(trunk length/100)2), was significantly lower for the oophorectomy group compared with the group treated by estrogen replacement therapy plus progesterone and estrogen replacement therapy groups (p = 0.018). When covaried for body mass index, trabecular bone volume percentage of a midsagittal section of L-1 was not significantly different between groups, but the adjusted mean was greatest in the estrogen replacement therapy plus progesterone group, followed closely by the estrogen replacement therapy group, and was least in the oophorectomy group. When covaried for body mass index, trabecular plate number was significantly lower (p = 0.022) and mean trabecular plate separation was significantly higher (p = 0.033) in the oophorectomy group. Thus both estrogen replacement therapy and estrogen replacement therapy plus progesterone provided overall protection against surgical menopause--associated bone mass loss. Cynomolgus macaques are an extremely useful animal model for estrogen replacement therapy use in prevention of postmenopausal bone loss.
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PMID:Effects on bone of surgical menopause and estrogen therapy with or without progesterone replacement in cynomolgus monkeys. 238 53

There is now a large body of evidence suggesting that the decline in ovarian function with menopause is associated with spontaneous increases in proinflammatory cytokines. The cytokines that have obtained the most attention are IL-1, IL-6, and TNF-alpha. The exact mechanisms by which estrogen interferes with cytokine activity are still incompletely known but may potentially include interactions of the ER with other transcription factors, modulation of nitric oxide activity, antioxidative effects, plasma membrane actions, and changes in immune cell function. Experimental and clinical studies strongly support a link between the increased state of proinflammatory cytokine activity and postmenopausal bone loss. Preliminary evidence suggests that these changes also might be relevant to vascular homeostasis and the development of atherosclerosis. Better knowledge of the mechanisms and the time course of these interactions may open new avenues for the prevention and treatment of some of the most prevalent and important disorders in postmenopausal women.
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PMID:Changes in proinflammatory cytokine activity after menopause. 1184 45

This long-term study (2 years) was designed to compare the effects of tibolone (LoTib at 0.05 mg/kg and HiTib at 0.2 mg/kg) with those of conjugated equine oestrogens (CEE) alone (0.042 mg/kg) and CEE continuously combined with medroxyprogesterone acetate (MPA) (0.167 mg/kg) on coronary artery atherosclerosis, bone, mammary gland and uterus in ovariectomised cynomolgus monkeys fed a moderately atherogenic diet. Despite reductions in plasma concentrations of high density lipoprotein cholesterol in tibolone-treated monkeys, there was no exacerbation of coronary artery atherosclerosis. Tibolone was equivalent to, or slightly better than, CEE and CEE + MPA in protecting against postmenopausal bone loss and loss of bone strength. Tibolone also resulted in less stimulation of breast and endometrial tissue compared with CEE and CEE + MPA. In conclusion, the results suggest that tibolone is a cardiovascular-safe treatment that is effective for the prevention of osteoporosis and that may have advantages over CEE or CEE + MPA with regard to endometrial and breast safety.
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PMID:Multisystem evaluations of the long-term effects of tibolone on postmenopausal monkeys. 1533 45

The successful use of renal replacement therapy has resulted in longer survival and a population of older patients with chronic kidney disease (CKD) that includes patients with other significant preexisting illnesses. In this review, we analyze the short-term and long-term outcomes associated to persisting hypogonadism in CKD patients. The short-term manifestations, commonly observed in normal postmenopausal women, are either a rare complaint of women with CKD or are frequently attributed to the uremic state. These symptoms include hot flashes, sleep disturbances and depression, sexual dysfunction, vaginal dryness and atrophy, urinary incontinence, and skin aging and wrinkling. The long-term outcomes of hypogonadism have potentially devastating effects on bone, cardiovascular system, and cognitive function, which could significantly alter the quality of life and survival of women with stage 5 CKD (CKD-5). Postmenopausal osteoporosis has been recognized as an important entity associated with renal osteodystrophy, and efforts have begun to tackle the reduced bone-mineral density (BMD) and increased fracture rate seen in this population. Similarly, cardiovascular disease represents the major cause of death in the CKD-5 population, with a 10 to 20 times greater mortality than in the general population. The accumulating evidence for a possible link between osteoporosis and atherosclerosis is discussed, as well as new directions in the understanding of postmenopausal osteoporosis in the context of renal bone disease, under the guidance of the Global Bone and Mineral Initiative endorsed by the Kidney Disease: Improving Global Outcomes initiative. Nephrologists must face gynecological issues with their women patients and design interdisciplinary clinical studies that include strategies that utilize well-tested and newer drug regimens in the management of osteoporosis, cardiovascular disease, and other postmenopausal manifestations in CKD-5 patients.
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PMID:Outcomes associated with hypogonadism in women with chronic kidney disease. 1549 73