Developmental mechanism for calcific aortic valve disease_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

HE Yubin ,  ZHU Dan

Department of Cardiac Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, P.R.China;

Corresponding author：

ZHU Dan, Email: zhudanmd@163.com

Keywords：

Aortic valve; calcification; inflammation; lipid metabolism; miRNA; long non-coding RNAs

DOI：

10.7507/1007-4848.201704033

Video：

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Calcific aortic valve disease has been the most common heart valve disorder in western world, accompanying with the increase of morbidity in our country year by year. Several molecules and mechanisms are involved in the progression of aortic valve calcification, which intensify the complexity of this pathological process. It is known that inflammation, a key factor in many diseases, has its own role in the development of aortic valve calcification. It has been demonstrated that inflammation, one of the most important participants in this disorder, which may accelerate the local lesions in aortic valve via promoting the expression of osteogenic differentiation of associated factors or decreasing the level of protective molecules. Dyslipidemia is a traditional risk factor of cardiovascular events. However, it may induce or enhance the inflammatory response whereby facilitates the calcific lesions in aortic valve. Recently, several researches have illustrated that non-coding RNAs, a stimulative factor in the progression of malignant tumor, might play a role in the development of aortic valve calcification. MiRNA and lncRNA, the non-coding RNAs which regulate the expression of genes involved in inflammatory and osteogenic differentiation, are undeniable regulators of aortic valve calcification.

Citation： HE Yubin, ZHU Dan. Developmental mechanism for calcific aortic valve disease. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2018, 25(2): 171-176. doi: 10.7507/1007-4848.201704033 Copy

1.	American College of Cardiology/American Heart Association Task Force on Practice Guidelines, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. Circulation, 2006, 114(5): e84-e231.
2.	Carabello BA, Paulus WJ. Aortic stenosis. Lancet, 2009, 373(9667): 956-966.
3.	Lind L. Comment on JIM-16-0640.R1. 'Mortality from aortic stenosis-prospective study of serum calcium and phosphate' by D. Wald. J Intern Med, 2017, 281(4): 412-413.
4.	Carità P, Coppola G, Novo G, et al. Aortic stenosis: insights on pathogenesis and clinical implications. J Geriatr Cardiol, 2016, 13(6): 489-498.
5.	Libby P, Aikawa M. Mechanisms of plaque stabilization with statins. Am J Cardiol, 2003, 91(4A): 4B-8B.
6.	Dunning J, Gao H, Chambers J, et al. Aortic valve surgery: marked increases in volume and significant decreases in mechanical valve use——an analysis of 41,227 patients over 5 years from the Society for Cardiothoracic Surgery in Great Britain and Ireland National database. J Thorac Cardiovasc Surg, 2011, 142(4): 776-782.
7.	Ten Kate GR, Bos S, Dedic A, et al. Increased aortic valve calcification in familial hypercholesterolemia: prevalence, extent, and associated risk factors. J Am Coll Cardiol, 2015, 66(24): 2687-2695.
8.	Rajamannan NM, Subramaniam M, Springett M, et al. Atorvastatin inhibits hypercholesterolemia-induced cellular proliferation and bone matrix production in the rabbit aortic valve. Circulation, 2002, 105(22): 2660-2665.
9.	Mathieu P, Bouchareb R, Boulanger MC. Innate and adaptive immunity in calcific aortic valve disease. J Immunol Res, 2015, 2015: 851945.
10.	Yang H, Mohamed AS, Zhou SH. Oxidized low density lipoprotein, stem cells, and atherosclerosis. Lipids Health Dis, 2012, 11: 85.
11.	Lichtman AH, Binder CJ, Tsimikas S, et al. Adaptive immunity in atherogenesis: new insights and therapeutic approaches. J Clin Invest, 2013, 123(1): 27-36.
12.	Côté N, Pibarot P, Pépin A, et al. Oxidized low-density lipoprotein, angiotensin II and increased waist cirumference are associated with valve inflammation in prehypertensive patients with aortic stenosis. Int J Cardiol, 2010, 145(3): 444-449.
13.	Capoulade R, Chan KL, Yeang C, et al. Oxidized phospholipids, lipoprotein(a), and progression of calcific aortic valve stenosis. J Am Coll Cardiol, 2015, 66(11): 1236-1246.
14.	Mahmut A, Boulanger MC, El Husseini D, et al. Elevated expression of lipoprotein-associated phospholipase A2 in calcific aortic valve disease: implications for valve mineralization. J Am Coll Cardiol, 2014, 63(5): 460-469.
15.	Oury C, Servais L, Bouznad N, et al. MicroRNAs in valvular heart diseases: potential role as markers and actors of valvular and cardiac remodeling. Int J Mol Sci, 2016, 17(7). pii: E1120.
16.	Pillai ICL, Li S, Romay M, et al. Cardiac fibroblasts adopt osteogenic fates and can be targeted to attenuate pathological heart calcification. Cell Stem Cell, 2017, 20(2): 218-232.
17.	Shapiro MD, Fazio S. Apolipoprotein B-containing lipoproteins and atherosclerotic cardiovascular disease. F1000Res, 2017, 6: 134.
18.	Cao J, Steffen BT, Budoff M, et al. Lipoprotein(a) levels are associated with subclinical calcific aortic valve disease in white and black individuals: the multi-ethnic study of atherosclerosis. Arterioscler Thromb Vasc Biol, 2016, 36(5): 1003-1009.
19.	Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, et al. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA, 2009, 301(22): 2331-2339.
20.	Clarke R, Peden JF, Hopewell JC, et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med, 2009, 361(26): 2518-2528.
21.	Thanassoulis G, Campbell CY, Owens DS, et al. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med, 2013, 368(6): 503-512.
22.	Galeone A, Paparella D, Colucci S, et al. The role of TNF-α and TNF superfamily members in the pathogenesis of calcific aortic valvular disease. Scien World J, 2013, 2013: 875363.
23.	Wu B, Wang Y, Xiao F, et al. Developmental mechanisms of aortic valve malformation and disease. Annu Rev Physiol, 2017, 79: 21-41.
24.	Kaden JJ, Kiliç R, Sarikoç A, et al. Tumor necrosis factor alpha promotes an osteoblast-like phenotype in human aortic valve myofibroblasts: a potential regulatory mechanism of valvular calcification. Int J Mol Med, 2005, 16(5): 869-872.
25.	Aggarwal BB. Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol, 2003, 3(9): 745-756.
26.	El Husseini D, Boulanger MC, Mahmut A, et al. P2Y2 receptor represses IL-6 expression by valve interstitial cells through Akt: implication for calcific aortic valve disease. J Mol Cell Cardiol, 2014, 72: 146-156.
27.	Zhou J, Zhu J, Jiang L, et al. Interleukin 18 promotes myofibroblast activation of valvular interstitial cells. Int J Cardiol, 2016, 221: 998-1003.
28.	DoiT, Sakoda T, Akagami T, et al. Aldosterone induces interleukin-18 through endothelin-1, angiotensin II, Rho/Rho-kinase, and PPARs in cardiomyocytes. Am J Physiol Heart Circ Physiol, 2008, 295(3): H1279-H1287.
29.	Dinarello CA, Nold-Petry C, Nold M, et al. Suppression of innate inflammation and immunity by interleukin-37. Eur J Immunol, 2016, 46(5): 1067-1081.
30.	Zeng Q, Song R, Fullerton DA, et al. Interleukin-37 suppresses the osteogenic responses of human aortic valve interstitial cells in vitro and alleviates valve lesions in mice. Proc Natl Acad Sci USA, 2017, 114(7): 1631-1636.
31.	Du Y, Wang Y, Wang L, et al. Cartilage oligomeric matrix protein inhibits vascular smooth muscle calcification by interacting with bone morphogenetic protein-2. Circ Res, 2011, 108(8): 917-928.
32.	Song R, Fullerton DA, Ao L, et al. An epigenetic regulatory loop controls pro-osteogenic activation by TGF-β1 or bone morphogenetic protein 2 in human aortic valve interstitial cells. J Biol Chem, 2017, 292(21): 8657-8666.
33.	Song R, Fullerton DA, Ao L, et al. BMP-2 and TGF-β1 mediate biglycan-induced pro-osteogenic reprogramming in aortic valve interstitial cells. J Mol Med (Berl), 2015, 93(4): 403-412.
34.	Imamura T, Oshima Y, Hikita A. Regulation of TGF-β family signalling by ubiquitination and deubiquitination. J Biochem, 2013, 154(6): 481-489.
35.	Winchester R, Wiesendanger M, O'Brien W, et al. Circulating activated and effector memory T cells are associated with calcification and clonal expansions in bicuspid and tricuspid valves of calcific aortic stenosis. J Immunol, 2011, 187(2): 1006-1014.
36.	Ohukainen P, Syväranta S, Näpänkangas J, et al. MicroRNA-125b and chemokine CCL4 expression are associated with calcific aortic valve disease. Ann Med, 2015, 47(5): 423-429.
37.	Nigam V, Sievers HH, Jensen BC, et al. Altered microRNAs in bicuspid aortic valve: a comparison between stenotic and insufficient valves. J Heart Valve Dis, 2010, 19(4): 459-465.
38.	Nigam V, Srivastava D. Notch1 represses osteogenic pathways in aortic valve cells. J Mol Cell Cardiol, 2009, 47(6): 828-834.
39.	El Accaoui RN, Gould ST, Hajj GP, et al. Aortic valve sclerosis in mice deficient in endothelial nitric oxide synthase. Am J Physiol Heart Circ Physiol, 2014, 306(9): H1302-H1313.
40.	Pan S, Zheng Y, Zhao R, et al. MicroRNA-130b and microRNA-374b mediate the effect of maternal dietary protein on offspring lipid metabolism in Meishan pigs. Br J Nutr, 2013, 109(10): 1731-1738.
41.	Li G, Qiao W, Zhang W, et al. The shift of macrophages toward M1 phenotype promotes aortic valvular calcification. J Thorac Cardiovasc Surg, 2017, 153(6): 1318-1327.
42.	Romaine SP, Tomaszewski M, Condorelli G, et al. MicroRNAs in cardiovascular disease: an introduction for clinicians. Heart, 2015, 101(12): 921-928.
43.	Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet, 2009, 10(3): 155-159.
44.	Fu XD. Non-coding RNA: a new frontier in regulatory biology. Natl Sci Rev, 2014, 1(2): 190-204.
45.	Carrion K, Dyo J, Patel V, et al. The long non-coding HOTAIR is modulated by cyclic stretch and WNT/β-CATENIN in human aortic valve cells and is a novel repressor of calcification genes. PLoS One, 2014, 9(5): e96577.
46.	Matouk I, Raveh E, Ohana P, et al. The increasing complexity of the oncofetal h19 gene locus: functional dissection and therapeutic intervention. Int J Mol Sci, 2013, 14(2): 4298-4316.
47.	Jang WG, Kim EJ, Kim DK, et al. BMP2 protein regulates osteocalcin expression via Runx2-mediated Atf6 gene transcription. J Biol Chem, 2012, 287(2): 905-915.
48.	Liang WC, Fu WM, Wang YB, et al. H19 activates Wnt signaling and promotes osteoblast differentiation by functioning as a competing endogenous RNA. Sci Rep, 2016, 6: 20121.
49.	Hadji F, Boulanger MC, Guay SP, et al. Altered DNA Methylation of Long Noncoding RNA H19 in Calcific Aortic Valve Disease Promotes Mineralization by Silencing NOTCH1. Circulation, 2016, 134(23): 1848-1862.
50.	Lefort K, Mandinova A, Ostano P, et al. Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCKalpha kinases. Genes Dev, 2007, 21(5): 562-577.

1. American College of Cardiology/American Heart Association Task Force on Practice Guidelines, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. Circulation, 2006, 114(5): e84-e231.
2. Carabello BA, Paulus WJ. Aortic stenosis. Lancet, 2009, 373(9667): 956-966.
3. Lind L. Comment on JIM-16-0640.R1. 'Mortality from aortic stenosis-prospective study of serum calcium and phosphate' by D. Wald. J Intern Med, 2017, 281(4): 412-413.
4. Carità P, Coppola G, Novo G, et al. Aortic stenosis: insights on pathogenesis and clinical implications. J Geriatr Cardiol, 2016, 13(6): 489-498.
5. Libby P, Aikawa M. Mechanisms of plaque stabilization with statins. Am J Cardiol, 2003, 91(4A): 4B-8B.
6. Dunning J, Gao H, Chambers J, et al. Aortic valve surgery: marked increases in volume and significant decreases in mechanical valve use——an analysis of 41,227 patients over 5 years from the Society for Cardiothoracic Surgery in Great Britain and Ireland National database. J Thorac Cardiovasc Surg, 2011, 142(4): 776-782.
7. Ten Kate GR, Bos S, Dedic A, et al. Increased aortic valve calcification in familial hypercholesterolemia: prevalence, extent, and associated risk factors. J Am Coll Cardiol, 2015, 66(24): 2687-2695.
8. Rajamannan NM, Subramaniam M, Springett M, et al. Atorvastatin inhibits hypercholesterolemia-induced cellular proliferation and bone matrix production in the rabbit aortic valve. Circulation, 2002, 105(22): 2660-2665.
9. Mathieu P, Bouchareb R, Boulanger MC. Innate and adaptive immunity in calcific aortic valve disease. J Immunol Res, 2015, 2015: 851945.
10. Yang H, Mohamed AS, Zhou SH. Oxidized low density lipoprotein, stem cells, and atherosclerosis. Lipids Health Dis, 2012, 11: 85.
11. Lichtman AH, Binder CJ, Tsimikas S, et al. Adaptive immunity in atherogenesis: new insights and therapeutic approaches. J Clin Invest, 2013, 123(1): 27-36.
12. Côté N, Pibarot P, Pépin A, et al. Oxidized low-density lipoprotein, angiotensin II and increased waist cirumference are associated with valve inflammation in prehypertensive patients with aortic stenosis. Int J Cardiol, 2010, 145(3): 444-449.
13. Capoulade R, Chan KL, Yeang C, et al. Oxidized phospholipids, lipoprotein(a), and progression of calcific aortic valve stenosis. J Am Coll Cardiol, 2015, 66(11): 1236-1246.
14. Mahmut A, Boulanger MC, El Husseini D, et al. Elevated expression of lipoprotein-associated phospholipase A2 in calcific aortic valve disease: implications for valve mineralization. J Am Coll Cardiol, 2014, 63(5): 460-469.
15. Oury C, Servais L, Bouznad N, et al. MicroRNAs in valvular heart diseases: potential role as markers and actors of valvular and cardiac remodeling. Int J Mol Sci, 2016, 17(7). pii: E1120.
16. Pillai ICL, Li S, Romay M, et al. Cardiac fibroblasts adopt osteogenic fates and can be targeted to attenuate pathological heart calcification. Cell Stem Cell, 2017, 20(2): 218-232.
17. Shapiro MD, Fazio S. Apolipoprotein B-containing lipoproteins and atherosclerotic cardiovascular disease. F1000Res, 2017, 6: 134.
18. Cao J, Steffen BT, Budoff M, et al. Lipoprotein(a) levels are associated with subclinical calcific aortic valve disease in white and black individuals: the multi-ethnic study of atherosclerosis. Arterioscler Thromb Vasc Biol, 2016, 36(5): 1003-1009.
19. Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, et al. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA, 2009, 301(22): 2331-2339.
20. Clarke R, Peden JF, Hopewell JC, et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med, 2009, 361(26): 2518-2528.
21. Thanassoulis G, Campbell CY, Owens DS, et al. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med, 2013, 368(6): 503-512.
22. Galeone A, Paparella D, Colucci S, et al. The role of TNF-α and TNF superfamily members in the pathogenesis of calcific aortic valvular disease. Scien World J, 2013, 2013: 875363.
23. Wu B, Wang Y, Xiao F, et al. Developmental mechanisms of aortic valve malformation and disease. Annu Rev Physiol, 2017, 79: 21-41.
24. Kaden JJ, Kiliç R, Sarikoç A, et al. Tumor necrosis factor alpha promotes an osteoblast-like phenotype in human aortic valve myofibroblasts: a potential regulatory mechanism of valvular calcification. Int J Mol Med, 2005, 16(5): 869-872.
25. Aggarwal BB. Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol, 2003, 3(9): 745-756.
26. El Husseini D, Boulanger MC, Mahmut A, et al. P2Y2 receptor represses IL-6 expression by valve interstitial cells through Akt: implication for calcific aortic valve disease. J Mol Cell Cardiol, 2014, 72: 146-156.
27. Zhou J, Zhu J, Jiang L, et al. Interleukin 18 promotes myofibroblast activation of valvular interstitial cells. Int J Cardiol, 2016, 221: 998-1003.
28. DoiT, Sakoda T, Akagami T, et al. Aldosterone induces interleukin-18 through endothelin-1, angiotensin II, Rho/Rho-kinase, and PPARs in cardiomyocytes. Am J Physiol Heart Circ Physiol, 2008, 295(3): H1279-H1287.
29. Dinarello CA, Nold-Petry C, Nold M, et al. Suppression of innate inflammation and immunity by interleukin-37. Eur J Immunol, 2016, 46(5): 1067-1081.
30. Zeng Q, Song R, Fullerton DA, et al. Interleukin-37 suppresses the osteogenic responses of human aortic valve interstitial cells in vitro and alleviates valve lesions in mice. Proc Natl Acad Sci USA, 2017, 114(7): 1631-1636.
31. Du Y, Wang Y, Wang L, et al. Cartilage oligomeric matrix protein inhibits vascular smooth muscle calcification by interacting with bone morphogenetic protein-2. Circ Res, 2011, 108(8): 917-928.
32. Song R, Fullerton DA, Ao L, et al. An epigenetic regulatory loop controls pro-osteogenic activation by TGF-β1 or bone morphogenetic protein 2 in human aortic valve interstitial cells. J Biol Chem, 2017, 292(21): 8657-8666.
33. Song R, Fullerton DA, Ao L, et al. BMP-2 and TGF-β1 mediate biglycan-induced pro-osteogenic reprogramming in aortic valve interstitial cells. J Mol Med (Berl), 2015, 93(4): 403-412.
34. Imamura T, Oshima Y, Hikita A. Regulation of TGF-β family signalling by ubiquitination and deubiquitination. J Biochem, 2013, 154(6): 481-489.
35. Winchester R, Wiesendanger M, O'Brien W, et al. Circulating activated and effector memory T cells are associated with calcification and clonal expansions in bicuspid and tricuspid valves of calcific aortic stenosis. J Immunol, 2011, 187(2): 1006-1014.
36. Ohukainen P, Syväranta S, Näpänkangas J, et al. MicroRNA-125b and chemokine CCL4 expression are associated with calcific aortic valve disease. Ann Med, 2015, 47(5): 423-429.
37. Nigam V, Sievers HH, Jensen BC, et al. Altered microRNAs in bicuspid aortic valve: a comparison between stenotic and insufficient valves. J Heart Valve Dis, 2010, 19(4): 459-465.
38. Nigam V, Srivastava D. Notch1 represses osteogenic pathways in aortic valve cells. J Mol Cell Cardiol, 2009, 47(6): 828-834.
39. El Accaoui RN, Gould ST, Hajj GP, et al. Aortic valve sclerosis in mice deficient in endothelial nitric oxide synthase. Am J Physiol Heart Circ Physiol, 2014, 306(9): H1302-H1313.
40. Pan S, Zheng Y, Zhao R, et al. MicroRNA-130b and microRNA-374b mediate the effect of maternal dietary protein on offspring lipid metabolism in Meishan pigs. Br J Nutr, 2013, 109(10): 1731-1738.
41. Li G, Qiao W, Zhang W, et al. The shift of macrophages toward M1 phenotype promotes aortic valvular calcification. J Thorac Cardiovasc Surg, 2017, 153(6): 1318-1327.
42. Romaine SP, Tomaszewski M, Condorelli G, et al. MicroRNAs in cardiovascular disease: an introduction for clinicians. Heart, 2015, 101(12): 921-928.
43. Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet, 2009, 10(3): 155-159.
44. Fu XD. Non-coding RNA: a new frontier in regulatory biology. Natl Sci Rev, 2014, 1(2): 190-204.
45. Carrion K, Dyo J, Patel V, et al. The long non-coding HOTAIR is modulated by cyclic stretch and WNT/β-CATENIN in human aortic valve cells and is a novel repressor of calcification genes. PLoS One, 2014, 9(5): e96577.
46. Matouk I, Raveh E, Ohana P, et al. The increasing complexity of the oncofetal h19 gene locus: functional dissection and therapeutic intervention. Int J Mol Sci, 2013, 14(2): 4298-4316.
47. Jang WG, Kim EJ, Kim DK, et al. BMP2 protein regulates osteocalcin expression via Runx2-mediated Atf6 gene transcription. J Biol Chem, 2012, 287(2): 905-915.
48. Liang WC, Fu WM, Wang YB, et al. H19 activates Wnt signaling and promotes osteoblast differentiation by functioning as a competing endogenous RNA. Sci Rep, 2016, 6: 20121.
49. Hadji F, Boulanger MC, Guay SP, et al. Altered DNA Methylation of Long Noncoding RNA H19 in Calcific Aortic Valve Disease Promotes Mineralization by Silencing NOTCH1. Circulation, 2016, 134(23): 1848-1862.
50. Lefort K, Mandinova A, Ostano P, et al. Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCKalpha kinases. Genes Dev, 2007, 21(5): 562-577.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Developmental mechanism for calcific aortic valve disease

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