Effect of raloxifene on proliferation and apoptosis of human aortic valve interstitial cells_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

 FUZhimin ¹ , LIUJianxin ² , LIMingpeng ³ , LUOBin ⁴

1. Department of Thoracic-cardiovascular Surgery, Chenzhou First People’s Hospital of Hunan Province, Chenzhou, Hunan 423000, P.R.China;
2. Department of Thoracic-cardiovascular Surgery, The Third Xiangya Hospital of Central South University, Changsha, 410013, P.R.China;
3. Department of Cardiology, Chenzhou First People’s Hospital of Hunan Province, Chenzhou, Hunan 423000, P.R.China;
4. Department of Cardiac Surgery, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, 518020, P.R.China;

Corresponding author：

FUZhimin, Email: fzmjinan2006@126.com

Keywords：

Raloxifene; aortic valve interstitial cells; proliferation; apoptosis

DOI：

10.7507/1007-4848.201507053

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effect of different concentrations of raloxifene (RAL) on the proliferation and apoptosis of human aortic valve interstitial cells (AVICs) in vitro. Methods AVICs were isolated from human aortic valve by collagenase type Ⅱ, and cultured in different concentrations (0 nmol/L, 0.1 nmol/L, 1 nmol/L,10 nmol/L, 100 nmol/L and 1 000 nmol/L) of RAL. AVICs cultured in 0 nmol/L RAL were treated as the control group and those in other concentrations of RAL as the experiment groups. The proliferation and apoptosis of AVICs were evaluated by Cell Proliferation Assay (MTS assay) on day 0, 3, 5, 7 and 9. Flow cytometry was used to detect the cell cycle and apoptosis of AVICs on day 7. Results MTS results showed that the optical density value at 490 nm was much less in 10 nmol/L RAL and 100 nmol/L RAL groups (P＜0.05) on day 5, 7 and 9 than that in the control group. Flow cytometry results demonstrated that S-phase rate (P＜0.05) and cell apoptosis rate (P＜0.05) on day 7 were lower in the 10 nmol/L and 100 nmol/L RAL groups compared with the control group. Conclusion RAL with suitable concentration can inhibit proliferation and apoptosis of AVICs, which will lay an important foundation for further research of the role of RAL on heart valve diseases.

Citation： FUZhimin, LIUJianxin, LIMingpeng, LUOBin. Effect of raloxifene on proliferation and apoptosis of human aortic valve interstitial cells. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2017, 24(2): 143-146. doi: 10.7507/1007-4848.201507053 Copy

1.	Eren E, Ellidag HY, Cekin Y, et al. Heart valve disease: the role of calcidiol deficiency, elevated parathyroid hormone levels and oxidative stress in mitral and aortic valve insufficiency. Redox Rep, 2014, 19(1): 34-39.
2.	Talluto CJ, Silverman NH. Aortic and mitral valve stenosis with regurgitation: not due to rheumatic heart disease. Echocar- diography, 2011, 28(2): E24-E27.
3.	Venardos N, Nadlonek NA, Zhan Q, et al. Aortic valve calcification is mediated by a differential response of aortic valve interstitial cells to inflammation. J Surg Res, 2014, 190(1): 1-8.
4.	Chung MT, Cheng PY, Lam KK, et al. Cardioprotective effects of long-term treatment with raloxifene, a selective estrogen receptor modulator, on myocardial ischemia/reperfusion injury in ovariectomized rats. Menopause, 2010, 17(1): 127-134.
5.	Stamatelopoulos KS, Lekakis JP, Poulakaki NA, et al. Tamoxifen improves endothelial function and reduces carotid intima-media thickness in postmenopausal women. Am Heart J, 2004, 147(6): 1093-1099.
6.	Mulholland DL, Gotlieb AI. Cell biology of valvular interstitial cells. Can J Cardiol, 1996, 12(3): 231-236.
7.	Rosenhek R, Binder T, Porenta G, et al. Predictors of outcome in severe, asymptomatic aortic stenosis. N Engl J Med, 2000, 343(9): 611-617.
8.	Vamvakidou A, Karogiannis N, Ramzy I, et al. Exercise echocardiography in asymptomatic severe aortic stenosis. Int J Cardiovasc Imaging, 2015, 31(8): 1561-1562.
9.	Gu X, Masters KS. Role of the Rho pathway in regulating valvular interstitial cell phenotype and nodule formation. Am J Physiol Heart Circ Physiol, 2011, 300(2): H448-H458.
10.	Kumar A, Wiltz DC, Grande-Allen KJ. Gentamicin reduces calcific nodule formation by aortic valve interstitial cells. Cardiovasc Eng Technol, 2013, 4(1): 16-25.
11.	Rajamannan NM, Sangiorgi G, Springett M, et al. Experimental hypercholesterolemia induces apoptosis in the aortic valve. J Heart Valve Dis, 2001, 10(3): 371-374.
12.	Chu Y, Lund DD, Weiss RM, et al. Pioglitazone attenuates valvular calcification induced by hypercholesterolemia. Arterioscler Thromb Vasc Biol, 2013, 33(3): 523-532.
13.	Jian B, Narula N, Li QY, et al. Progression of aortic valve stenosis: TGF-beta1 is present in calcified aortic valve cusps and promotes aortic valve interstitial cell calcification via apoptosis. Ann Thorac Surg, 2003, 75(2): 457-465.
14.	Pickar JH, Komm BS. Selective estrogen receptor modulators and the combination therapy conjugated estrogens/bazedoxifene: A review of effects on the breast. Post Reprod Health, 2015, 21(3): 112-121.
15.	Meier C, Lamy O, Krieg MA, et al. The role of teriparatide in sequential and combination therapy of osteoporosis. Swiss Med Wkly, 2014, 144. w13952.
16.	Lamas AZ, Caliman IF, Dalpiaz PL, et al. Comparative effects of estrogen, raloxifene and tamoxifen on endothelial dysfunction, inflammatory markers and oxidative stress in ovariectomized rats. Life Sci, 2015, 124: 101-109.
17.	Sumino H, Ichikawa S, Kasama S, et al. Effects of raloxifene on brachial arterial endothelial function, carotid wall thickness, and arterial stiffness in osteoporotic postmenopausal women. Int Heart J, 2010, 51(1): 60-67.
18.	Meyer MR, Prossnitz ER, Barton M. The G protein-coupled estrogen receptor GPER/GPR30 as a regulator of cardiovascular function. Vascul Pharmacol, 2011, 55(1-3): 17-25.
19.	Poirot M, Silvente-Poirot S, Weichselbaum RR. Cholesterol metabolism and resistance to tamoxifen. Curr Opin Pharmacol, 2012, 12(6): 683-689.
20.	Shuvy M, Abedat S, Beeri R, et al. Raloxifene attenuates Gas6 and apoptosis in experimental aortic valve disease in renal failure. Am J Physiol Heart Circ Physiol, 2011, 300(5): H1829-H1840.

1. Eren E, Ellidag HY, Cekin Y, et al. Heart valve disease: the role of calcidiol deficiency, elevated parathyroid hormone levels and oxidative stress in mitral and aortic valve insufficiency. Redox Rep, 2014, 19(1): 34-39.
2. Talluto CJ, Silverman NH. Aortic and mitral valve stenosis with regurgitation: not due to rheumatic heart disease. Echocar- diography, 2011, 28(2): E24-E27.
3. Venardos N, Nadlonek NA, Zhan Q, et al. Aortic valve calcification is mediated by a differential response of aortic valve interstitial cells to inflammation. J Surg Res, 2014, 190(1): 1-8.
4. Chung MT, Cheng PY, Lam KK, et al. Cardioprotective effects of long-term treatment with raloxifene, a selective estrogen receptor modulator, on myocardial ischemia/reperfusion injury in ovariectomized rats. Menopause, 2010, 17(1): 127-134.
5. Stamatelopoulos KS, Lekakis JP, Poulakaki NA, et al. Tamoxifen improves endothelial function and reduces carotid intima-media thickness in postmenopausal women. Am Heart J, 2004, 147(6): 1093-1099.
6. Mulholland DL, Gotlieb AI. Cell biology of valvular interstitial cells. Can J Cardiol, 1996, 12(3): 231-236.
7. Rosenhek R, Binder T, Porenta G, et al. Predictors of outcome in severe, asymptomatic aortic stenosis. N Engl J Med, 2000, 343(9): 611-617.
8. Vamvakidou A, Karogiannis N, Ramzy I, et al. Exercise echocardiography in asymptomatic severe aortic stenosis. Int J Cardiovasc Imaging, 2015, 31(8): 1561-1562.
9. Gu X, Masters KS. Role of the Rho pathway in regulating valvular interstitial cell phenotype and nodule formation. Am J Physiol Heart Circ Physiol, 2011, 300(2): H448-H458.
10. Kumar A, Wiltz DC, Grande-Allen KJ. Gentamicin reduces calcific nodule formation by aortic valve interstitial cells. Cardiovasc Eng Technol, 2013, 4(1): 16-25.
11. Rajamannan NM, Sangiorgi G, Springett M, et al. Experimental hypercholesterolemia induces apoptosis in the aortic valve. J Heart Valve Dis, 2001, 10(3): 371-374.
12. Chu Y, Lund DD, Weiss RM, et al. Pioglitazone attenuates valvular calcification induced by hypercholesterolemia. Arterioscler Thromb Vasc Biol, 2013, 33(3): 523-532.
13. Jian B, Narula N, Li QY, et al. Progression of aortic valve stenosis: TGF-beta1 is present in calcified aortic valve cusps and promotes aortic valve interstitial cell calcification via apoptosis. Ann Thorac Surg, 2003, 75(2): 457-465.
14. Pickar JH, Komm BS. Selective estrogen receptor modulators and the combination therapy conjugated estrogens/bazedoxifene: A review of effects on the breast. Post Reprod Health, 2015, 21(3): 112-121.
15. Meier C, Lamy O, Krieg MA, et al. The role of teriparatide in sequential and combination therapy of osteoporosis. Swiss Med Wkly, 2014, 144. w13952.
16. Lamas AZ, Caliman IF, Dalpiaz PL, et al. Comparative effects of estrogen, raloxifene and tamoxifen on endothelial dysfunction, inflammatory markers and oxidative stress in ovariectomized rats. Life Sci, 2015, 124: 101-109.
17. Sumino H, Ichikawa S, Kasama S, et al. Effects of raloxifene on brachial arterial endothelial function, carotid wall thickness, and arterial stiffness in osteoporotic postmenopausal women. Int Heart J, 2010, 51(1): 60-67.
18. Meyer MR, Prossnitz ER, Barton M. The G protein-coupled estrogen receptor GPER/GPR30 as a regulator of cardiovascular function. Vascul Pharmacol, 2011, 55(1-3): 17-25.
19. Poirot M, Silvente-Poirot S, Weichselbaum RR. Cholesterol metabolism and resistance to tamoxifen. Curr Opin Pharmacol, 2012, 12(6): 683-689.
20. Shuvy M, Abedat S, Beeri R, et al. Raloxifene attenuates Gas6 and apoptosis in experimental aortic valve disease in renal failure. Am J Physiol Heart Circ Physiol, 2011, 300(5): H1829-H1840.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Effect of raloxifene on proliferation and apoptosis of human aortic valve interstitial cells

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