Cardioprotective effects of long-term treatment with raloxifene, a selective estrogen receptor modulator, on myocardial ischemia/reperfusion injury in ovariectomized rats

Chung, Ming-Ting; Cheng, Pao-Yun; Lam, Kwok-Keung; Chen, Shuying; Ting, Yi-Fan; Yen, Mao‐Hsiung; Lee, Yen-Mei

doi:10.1097/gme.0b013e3181b4c4ac

Cited by 31 publications

(15 citation statements)

References 43 publications

(40 reference statements)

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“…The connection between the MPO level and cardiac parameter or tissue HO expression suggests a preventive role of estrogen therapy in cardiovascular pathological processes. Similarly to our results, Chung et al demonstrated that long-term treatment with RAL significantly decreased the cardiac activity of MPO in OVX rat [40]. While OVX increases the inflammation processes, the elevated levels of inflammatory markers can be decreased with hormone replacement therapy [41].…”

Section: Discussionsupporting

confidence: 89%

Cardioprotective Effect of Selective Estrogen Receptor Modulator Raloxifene Are Mediated by Heme Oxygenase in Estrogen‐Deficient Rat

Pósa

Szabó

Kupai

et al. 2017

Oxidative Medicine and Cellular Longevity

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Estrogens and raloxifene (RAL) have beneficial effects on certain cardiovascular indices in postmenopausal women characterized by estrogen deficiency. Heme oxygenase (HO) activity is increased by 17β-estradiol (E2) and RAL in estrogen-deficient rat resulting in vasorelaxation mediated by carbon monoxide. We determined the expressions of HO in cardiac and aortic tissues after ovariectomy (OVX) and subsequent RAL or E2 treatment. We investigated the effects of pharmacological inhibition of HO enzyme on the arginine vasopressin- (AVP-) induced blood pressure in vivo, the epinephrine- and phentolamine-induced electrocardiogram ST segment changes in vivo, and the myeloperoxidase (MPO) enzyme activity. When compared with intact females, OVX decreased the HO-1 and HO-2 expression, aggravated the electrocardiogram signs of heart ischemia and the blood pressure response to AVP, and increased the cardiac MPO. E2 and RAL are largely protected against these negative impacts induced by OVX. The pharmacological inhibition of HO in E2- or RAL-treated OVX animals, however, restored the cardiovascular status close to that observed in nontreated OVX animals. The decreased expression of HO enzymes and the changes in blood pressure ischemia susceptibility and inflammatory state in OVX rat can be reverted by the administration of E2 or RAL partly through its antioxidant and anti-inflammatory roles.

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Section: Discussionsupporting

confidence: 89%

Cardioprotective Effect of Selective Estrogen Receptor Modulator Raloxifene Are Mediated by Heme Oxygenase in Estrogen‐Deficient Rat

Pósa

Szabó

Kupai

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…In addition, selective activation of ERβ provides cardioprotection that requires the availability of NO (Lin et al, 2009). Acute and chronic treatment of dogs or rodents with the SERM raloxifene also improves ischemia/reperfusion-related myocardial injury, and again partly involves NO-dependent mechanisms mediated by the PI 3 K/Akt-pathway (Chung et al, 2010; Nemcsik et al, 2004; Ogita et al, 2002; Ogita et al, 2004). A number of experimental studies on ischemia/reperfusion injury subsequently found beneficial effects mediated by both ERα and ERβ, yet some controversies exist whether both receptors provide acute and chronic cardioprotection (Deschamps et al, 2010).…”

Section: Protective Effects Of Gper On Myocardial Functionmentioning

confidence: 99%

The G protein-coupled estrogen receptor GPER/GPR30 as a regulator of cardiovascular function

Meyer

Prossnitz

Barton

2011

Vascular Pharmacology

139

104

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Endogenous estrogens are important regulators of cardiovascular homeostasis in premenopausal women and interfere with the development of hypertension and coronary artery disease. These hormones act via three different estrogen receptors affecting both gene transcription and rapid signaling pathways in a complex interplay. In addition to the classical estrogen receptors ERα and ERβ, which are known mediators of estrogen-dependent vascular effects, a G protein-coupled estrogen receptor termed GPER that is expressed in the cardiovascular system has recently been identified. Endogenous human 17β-estradiol, selective estrogen receptor modulators (SERMs) including tamoxifen and raloxifene, and selective estrogen receptor downregulators (SERDs) such as ICI 182,780 are all agonists of GPER, which has been implicated in the regulation of vasomotor tone and protection from myocardial ischemia/reperfusion injury. As a result, understanding the individual role of ERα, ERβ, and GPER in cardiovascular function has become increasingly complex. With accumulating evidence that GPER is responsible for a variety of beneficial cardiovascular effects of estrogens, this receptor may represent a novel target to develop effective strategies for the treatment of cardiovascular diseases by tissue-specific, selective activation of estrogen-dependent molecular pathways devoid of side effects seen with conventional hormone therapy.

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“…The function of vascular endothelial cell is regulated by RAL via estrogen response elements or other pathways to protect vascular endothelial function [6]. RAL is expected to become a potential drug for the treatment of cardiovascular disease [7, 8]. …”

Section: Introductionmentioning

confidence: 99%

Effects of Raloxifene on the Proliferation and Apoptosis of Human Aortic Valve Interstitial Cells

Luo

et al. 2016

BioMed Research International

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We aimed to explore the effects of raloxifene (RAL) on the proliferation and apoptosis of human aortic valve interstitial cells (AVICs). Different concentrations of RAL were used to act on AVICs. MTS kit is used to test the effects of different concentrations of RAL on the proliferation of AVICs. Cell cycle and apoptosis test used flow cytometry after seven-day treatment. The relative expression levels of caspase-3 and caspase-8 are tested with RT-qPCR and Western blot. The results of MTS testing revealed that the absorbance value (OD value) of the cells in the concentration groups of 10 and 100 nmol/L RAL at a wavelength of 490 nm at five, seven, and nine days significantly decreased compared with that in the control group. Meanwhile, the results of flow cytometry of the cells collected after seven days showed that the ratio of the S stage and the cell apoptosis rate of AVICs can be significantly reduced by RAL in the concentration groups of 10 and 100 nmol/L. The mRNA and protein expressions of caspase-3 and caspase-8 were significantly decreased compared with those in the control group. This study laid the foundation for further treatment of aortic valve disease by using RAL.

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Cardioprotective effects of long-term treatment with raloxifene, a selective estrogen receptor modulator, on myocardial ischemia/reperfusion injury in ovariectomized rats

Abstract: Long-term treatment with RAL can reduce the severity of MI-induced arrhythmias and attenuate MI/R-induced damages and apoptosis in Ovx rats. This cardioprotective effect of RAL may be associated with inhibition of neutrophil infiltration and suppression of nuclear factor-kappaB activation.

Cited by 31 publications

References 43 publications

Cardioprotective Effect of Selective Estrogen Receptor Modulator Raloxifene Are Mediated by Heme Oxygenase in Estrogen‐Deficient Rat

Cardioprotective Effect of Selective Estrogen Receptor Modulator Raloxifene Are Mediated by Heme Oxygenase in Estrogen‐Deficient Rat

The G protein-coupled estrogen receptor GPER/GPR30 as a regulator of cardiovascular function

Effects of Raloxifene on the Proliferation and Apoptosis of Human Aortic Valve Interstitial Cells

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