Estrogen-induced cardiorenal protection: potential cellular, biochemical, and molecular mechanisms

Dubey, Raghvendra K.; Jackson, Edwin K.

doi:10.1152/ajprenal.2001.280.3.f365

Cited by 229 publications

(226 citation statements)

References 303 publications

(397 reference statements)

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“…24 We demonstrated that the beneficial effect of ARB to improve vascular remodeling is caused by not only blockade of the AT 1 receptor but also stimulation of the unmasked AT 2 receptor by Ang II. 16 Therefore, it is possible that the effect of ARB is linked to the stimulation of AT 2 receptor-mediated signaling such as activation of protein tyrosine phosphatases, 25 which is further potentiated by estrogen.…”

Section: Liu Et Al Effect Of Estrogen and Arb On Vascular Remodeling 455mentioning

confidence: 83%

Effect of Estrogen and AT ₁ Receptor Blocker on Neointima Formation

et al. 2002

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Abstract-The present study explored the possibility that estrogen may enhance the inhibitory effect of an angiotensin (Ang) II type 1 (AT 1 ) receptor blocker on neointima formation in vascular injury, and investigated the signaling mechanism involved in their actions. Polyethylene cuff placement around the femoral artery of mice induced neointima formation and increased bromodeoxyuridine (BrdU) incorporation into vascular smooth muscle cells. These changes were significantly smaller in female mice than in male mice. Ovariectomy enhanced neointima formation and BrdU incorporation in the injured artery, which were reversed by 17␤-estradiol (80 g/kg per day) replacement. Treatment with a selective AT 1 receptor blocker, olmesartan (3 mg/kg per day), significantly inhibited neointima formation and BrdU incorporation, whereas the inhibitory effects of olmesartan were more marked in intact female mice than in male or ovariectomized mice. Phosphorylation of extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription (STAT) 1, and STAT3 was increased in the injured artery. These increases were significantly smaller in intact female mice than in male or ovariectomized mice. Olmesartan or estrogen attenuated the phosphorylation of ERK and STAT in the injured artery, whereas these inhibitory effects were greater in intact female mice. Lower doses of olmesartan (0.5 mg/kg per day) or 17␤-estradiol (20 g/kg per day) did not influence neointima formation, BrdU incorporation, and ERK and STAT phosphorylation in ovariectomized mice, whereas coadministration of olmesartan and 17␤-estradiol at these doses attenuated these parameters. These results indicate that estrogen and an AT 1 receptor blocker synergistically attenuate vascular remodeling, which is at least partly via inhibition of ERK and STAT activity.

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Section: Liu Et Al Effect Of Estrogen and Arb On Vascular Remodeling 455mentioning

confidence: 83%

Effect of Estrogen and AT ₁ Receptor Blocker on Neointima Formation

et al. 2002

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Section: Experimental Studies In Animals and Isolated Cells Suggest Tmentioning

confidence: 99%

“…27 In animals and isolated cells, estrogen induces multiple effects that in theory should reduce CHD risk. 27 For example, estrogen upregulates the synthesis of vasodilatory and growth inhibitory molecules such as nitric oxide, prostacyclin, cAMP, and adenosine. Also, estrogen downregulates the synthesis of vasoconstrictor molecules, growth inducers, and atherosclerosis inducers, such as endothelin, homocysteine, angiotensin II, renin activity, angiotensin-converting enzyme activity, catecholamines, and low-density lipoprotein.…”

Section: Experimental Studies In Animals and Isolated Cells Suggest Tmentioning

confidence: 99%

“…27 Because both ER-dependent and ER-independent mechanisms play a role in mediating the pharmacological actions of estradiol on the cardiovascular system, CEE and other estrogens may not mimic the cardiovascular protective effects of estradiol.…”

Section: Type Of Estrogenmentioning

confidence: 99%

“…For example, ethinyl estradiol, a nonestradiol estrogen, induces deleterious effects on the cardiovascular system. 27 A Swedish study 58 found a reduced risk of myocardial infarction for estradiol compared with oral estriol or vaginal estriol/dienoestrol.…”

Section: Type Of Estrogenmentioning

confidence: 99%

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Hormone Replacement Therapy and Cardiovascular Disease

et al. 2004

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Abstract-Observational studies in humans and experimental studies in animals and isolated cells supported the widely held belief that hormone replacement therapy protects the cardiovascular system from disease. To nearly everyone's astonishment, the Women's Health Initiative Study and the Heart and Estrogen/Progestin Replacement Study overturned the conclusion that hormone replacement therapy protects the cardiovascular system and, in fact, supported the opposite view that such therapy may actually increase the risk of cardiovascular disease. Observational Studies Suggest HRT Has Beneficial Cardiovascular EffectsIn modern societies, cardiovascular disease is the main cause of morbidity and mortality in men and women. Women, however, are comparatively spared. For example, in people younger than age 65 years, the prevalence of coronary heart disease (CHD) is several-fold higher in men. 3,4 Although CHD prevalence increases with age in both genders, before the age of 65 years the relationship between age and CHD prevalence is shifted rightward by 5 years in women; 5,6 compared with postmenopausal women, CHD deaths are rare in premenopausal women. 7 Autopsy studies demonstrated increased CHD in oophorectomized young women, 8 and several studies demonstrated an increased risk of cardiovascular disease in women with bilateral oophorectomy without HRT compared with those receiving HRT. 9,10 Women with natural early-onset menopause who did not use HRT had a greater likelihood for CHD compared with age-matched premenopausal women. 9,11 Also, studies reported an inverse relationship between age at natural menopause and mortality from CHD 12,13 and carotid atherosclerosis. 14 Bush et al demonstrated that HRT was associated with reduced all-cause mortality in postmenopausal women, 15 primarily because of favorable effects on high-density lipoprotein. 16 Barrett-Connor and Bush 8 reported that many, but not all, cross-sectional and prospective studies demonstrated a statistically significant reduction in CHD in women taking HRT, and Grady et al 17 presented a meta-analysis of published observational studies and reported that HRT was associated with one-third less fatal CHD. An up-to-date meta-analysis of 25 observational studies conducted between 1976 and 1996 showed that the relative risk for CHD in women who ever used HRT compared with never users was 0.70. 18 The Nurses' Health Study was a comprehensive investigation conducted in 121 700 female nurses aged 30 to 55 years. In the latest report, compiled with data from 70 533 postmenopausal women followed-up for 20 years, the overall risk of CHD in current users of HRT was reduced, with a relative risk of 0.61 after adjustment for age and cardiovascular risk factors. 19

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