Skip to main content
Top
Published in: Inflammation 3/2013

01-06-2013

Inflammation Is Associated with the Remodeling of Calcific Aortic Valve Disease

Authors: Nancy Coté, Ablajan Mahmut, Yohan Bosse, Christian Couture, Sylvain Pagé, Sylvain Trahan, Marie-Chloé Boulanger, Dominique Fournier, Philippe Pibarot, Patrick Mathieu

Published in: Inflammation | Issue 3/2013

Login to get access

Abstract

Calcific aortic valve disease (CAVD) is the most frequent heart valve disorder. Studies indicate that mineralization of the aortic valve may be related to the inflammatory process. However, no clear evidence has been given regarding clinical evolution of aortic stenosis and the inflammatory process within the aortic valve. Aortic valves excised from 285 patients with CAVD undergoing aortic valve replacement were analyzed for the presence of chronic inflammatory infiltrates, and those findings were related to the hemodynamic severity of aortic stenosis. In a subset of 57 patients, in whom additional valvular tissue and the clinical progression rate of aortic stenosis were available, the density of leukocytes was determined as well as the number of TNF-α transcripts. Histological analyses revealed that in 81 (28.4 %) patients, the presence of chronic inflammatory infiltrates was documented within CAVD tissue, which was characterized by the existence of a cluster of cells as well as the presence of neovascularisation and osseous metaplasia. The presence of an inflammatory process within the CAVD tissue was independently related to the remodeling process and the peak transaortic gradient. In addition, the density of leukocytes within CAVD tended to correlate (r = 0.25, p = 0.05) with the progression rate of aortic stenosis. Dense inflammatory infiltrate within CAVD is associated with an active remodeling process, the severity of aortic stenosis, and the hemodynamic progression rate.
Literature
1.
go back to reference Cote, C., P. Pibarot, J.P. Despres, D. Mohty, A. Cartier, B.J. Arsenault, C. Couture, and P. Mathieu. 2008. Association between circulating oxidised low-density lipoprotein and fibrocalcific remodelling of the aortic valve in aortic stenosis. Heart 94: 1175–1180.PubMedCrossRef Cote, C., P. Pibarot, J.P. Despres, D. Mohty, A. Cartier, B.J. Arsenault, C. Couture, and P. Mathieu. 2008. Association between circulating oxidised low-density lipoprotein and fibrocalcific remodelling of the aortic valve in aortic stenosis. Heart 94: 1175–1180.PubMedCrossRef
2.
go back to reference Messika-Zeitoun, D., M.C. Aubry, D. Detaint, L.F. Bielak, P.A. Peyser, P.F. Sheedy, S.T. Turner, J.F. Breen, C. Scott, A.J. Tajik, and M. Enriquez-Sarano. 2004. Evaluation and clinical implications of aortic valve calcification measured by electron-beam computed tomography. Circulation 110: 356–362.PubMedCrossRef Messika-Zeitoun, D., M.C. Aubry, D. Detaint, L.F. Bielak, P.A. Peyser, P.F. Sheedy, S.T. Turner, J.F. Breen, C. Scott, A.J. Tajik, and M. Enriquez-Sarano. 2004. Evaluation and clinical implications of aortic valve calcification measured by electron-beam computed tomography. Circulation 110: 356–362.PubMedCrossRef
3.
go back to reference Mohty, D., P. Pibarot, J.P. Despres, C. Cote, B. Arsenault, A. Cartier, P. Cosnay, C. Couture, and P. Mathieu. 2008. Association between plasma LDL particle size, valvular accumulation of oxidized LDL, and inflammation in patients with aortic stenosis. Arteriosclerosis, Thrombosis, and Vascular Biology 28: 187–193.PubMedCrossRef Mohty, D., P. Pibarot, J.P. Despres, C. Cote, B. Arsenault, A. Cartier, P. Cosnay, C. Couture, and P. Mathieu. 2008. Association between plasma LDL particle size, valvular accumulation of oxidized LDL, and inflammation in patients with aortic stenosis. Arteriosclerosis, Thrombosis, and Vascular Biology 28: 187–193.PubMedCrossRef
4.
go back to reference Rajamannan, N.M., F.J. Evans, E. Aikawa, K.J. Grande-Allen, L.L. Demer, D.D. Heistad, C.A. Simmons, K.S. Masters, P. Mathieu, K.D. O'Brien, F.J. Schoen, D.A. Towler, A.P. Yoganathan, and C.M. Otto. 2011. Calcific aortic valve disease: not simply a degenerative process: a review and agenda for research from the National Heart and Lung and Blood Institute Aortic Stenosis Working Group. Executive summary: calcific aortic valve disease—2011 update. Circulation 124: 1783–1791.PubMedCrossRef Rajamannan, N.M., F.J. Evans, E. Aikawa, K.J. Grande-Allen, L.L. Demer, D.D. Heistad, C.A. Simmons, K.S. Masters, P. Mathieu, K.D. O'Brien, F.J. Schoen, D.A. Towler, A.P. Yoganathan, and C.M. Otto. 2011. Calcific aortic valve disease: not simply a degenerative process: a review and agenda for research from the National Heart and Lung and Blood Institute Aortic Stenosis Working Group. Executive summary: calcific aortic valve disease—2011 update. Circulation 124: 1783–1791.PubMedCrossRef
5.
go back to reference Cowell, S.J., D.E. Newby, R.J. Prescott, P. Bloomfield, J. Reid, D.B. Northridge, and N.A. Boon. 2005. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. The New England Journal of Medicine 352: 2389–2397.PubMedCrossRef Cowell, S.J., D.E. Newby, R.J. Prescott, P. Bloomfield, J. Reid, D.B. Northridge, and N.A. Boon. 2005. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. The New England Journal of Medicine 352: 2389–2397.PubMedCrossRef
6.
go back to reference Rossebo, A.B., T.R. Pedersen, K. Boman, P. Brudi, J.B. Chambers, K. Egstrup, E. Gerdts, C. Gohlke-Barwolf, I. Holme, Y.A. Kesaniemi, W. Malbecq, C.A. Nienaber, S. Ray, T. Skjaerpe, K. Wachtell, and R. Willenheimer. 2008. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. The New England Journal of Medicine 359: 1343–1356.PubMedCrossRef Rossebo, A.B., T.R. Pedersen, K. Boman, P. Brudi, J.B. Chambers, K. Egstrup, E. Gerdts, C. Gohlke-Barwolf, I. Holme, Y.A. Kesaniemi, W. Malbecq, C.A. Nienaber, S. Ray, T. Skjaerpe, K. Wachtell, and R. Willenheimer. 2008. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. The New England Journal of Medicine 359: 1343–1356.PubMedCrossRef
7.
go back to reference Chan, K.L., K. Teo, J.G. Dumesnil, A. Ni, and J. Tam. 2010. Effect of lipid lowering with rosuvastatin on progression of aortic stenosis: results of the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial. Circulation 121: 306–314.PubMedCrossRef Chan, K.L., K. Teo, J.G. Dumesnil, A. Ni, and J. Tam. 2010. Effect of lipid lowering with rosuvastatin on progression of aortic stenosis: results of the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial. Circulation 121: 306–314.PubMedCrossRef
8.
go back to reference Otto, C.M. 2008. Calcific aortic stenosis—time to look more closely at the valve. The New England Journal of Medicine 359: 1395–1398.PubMedCrossRef Otto, C.M. 2008. Calcific aortic stenosis—time to look more closely at the valve. The New England Journal of Medicine 359: 1395–1398.PubMedCrossRef
9.
go back to reference Warren, B.A., and J.L. Yong. 1997. Calcification of the aortic valve: its progression and grading. Pathology 29: 360–368.PubMedCrossRef Warren, B.A., and J.L. Yong. 1997. Calcification of the aortic valve: its progression and grading. Pathology 29: 360–368.PubMedCrossRef
10.
go back to reference Wypasek, E., J. Natorska, G. Grudzien, G. Filip, J. Sadowski, and A. Undas. 2012. Mast cells in human stenotic aortic valves are associated with the severity of stenosis. Inflammation. doi:10.1007/s10753-012-9565-z. Wypasek, E., J. Natorska, G. Grudzien, G. Filip, J. Sadowski, and A. Undas. 2012. Mast cells in human stenotic aortic valves are associated with the severity of stenosis. Inflammation. doi:10.​1007/​s10753-012-9565-z.
11.
go back to reference Dweck, M.R., C. Jones, N.V. Joshi, A.M. Fletcher, H. Richardson, A. White, M. Marsden, R. Pessotto, J.C. Clark, W.A. Wallace, D.M. Salter, G. McKillop, E.J. van Beek, N.A. Boon, J.H. Rudd, and D.E. Newby. 2012. Assessment of valvular calcification and inflammation by positron emission tomography in patients with aortic stenosis. Circulation 125: 76–86.PubMedCrossRef Dweck, M.R., C. Jones, N.V. Joshi, A.M. Fletcher, H. Richardson, A. White, M. Marsden, R. Pessotto, J.C. Clark, W.A. Wallace, D.M. Salter, G. McKillop, E.J. van Beek, N.A. Boon, J.H. Rudd, and D.E. Newby. 2012. Assessment of valvular calcification and inflammation by positron emission tomography in patients with aortic stenosis. Circulation 125: 76–86.PubMedCrossRef
12.
go back to reference Yip, C.Y., and C.A. Simmons. 2011. The aortic valve microenvironment and its role in calcific aortic valve disease. Cardiovascular Pathology 20: 177–182.PubMedCrossRef Yip, C.Y., and C.A. Simmons. 2011. The aortic valve microenvironment and its role in calcific aortic valve disease. Cardiovascular Pathology 20: 177–182.PubMedCrossRef
13.
go back to reference Charest, A., A. Pepin, R. Shetty, C. Cote, P. Voisine, F. Dagenais, P. Pibarot, and P. Mathieu. 2006. Distribution of SPARC during neovascularisation of degenerative aortic stenosis. Heart 92: 1844–1849.PubMedCrossRef Charest, A., A. Pepin, R. Shetty, C. Cote, P. Voisine, F. Dagenais, P. Pibarot, and P. Mathieu. 2006. Distribution of SPARC during neovascularisation of degenerative aortic stenosis. Heart 92: 1844–1849.PubMedCrossRef
14.
go back to reference Mohler III, E.R., F. Gannon, C. Reynolds, R. Zimmerman, M.G. Keane, and F.S. Kaplan. 2001. Bone formation and inflammation in cardiac valves. Circulation 103: 1522–1528.PubMedCrossRef Mohler III, E.R., F. Gannon, C. Reynolds, R. Zimmerman, M.G. Keane, and F.S. Kaplan. 2001. Bone formation and inflammation in cardiac valves. Circulation 103: 1522–1528.PubMedCrossRef
15.
go back to reference Briand, M., I. Lemieux, J.G. Dumesnil, P. Mathieu, A. Cartier, J.P. Despres, M. Arsenault, J. Couet, and P. Pibarot. 2006. Metabolic syndrome negatively influences disease progression and prognosis in aortic stenosis. Journal of the American College of Cardiology 47: 2229–2236.PubMedCrossRef Briand, M., I. Lemieux, J.G. Dumesnil, P. Mathieu, A. Cartier, J.P. Despres, M. Arsenault, J. Couet, and P. Pibarot. 2006. Metabolic syndrome negatively influences disease progression and prognosis in aortic stenosis. Journal of the American College of Cardiology 47: 2229–2236.PubMedCrossRef
16.
go back to reference Briand, M., P. Pibarot, J.P. Despres, P. Voisine, J.G. Dumesnil, F. Dagenais, and P. Mathieu. 2006. Metabolic syndrome is associated with faster degeneration of bioprosthetic valves. Circulation 114: I512–I517.PubMedCrossRef Briand, M., P. Pibarot, J.P. Despres, P. Voisine, J.G. Dumesnil, F. Dagenais, and P. Mathieu. 2006. Metabolic syndrome is associated with faster degeneration of bioprosthetic valves. Circulation 114: I512–I517.PubMedCrossRef
17.
go back to reference Katz, R., N.D. Wong, R. Kronmal, J. Takasu, D.M. Shavelle, J.L. Probstfield, A.G. Bertoni, M.J. Budoff, and K.D. O'Brien. 2006. Features of the metabolic syndrome and diabetes mellitus as predictors of aortic valve calcification in the Multi-Ethnic Study of Atherosclerosis. Circulation 113: 2113–2119.PubMedCrossRef Katz, R., N.D. Wong, R. Kronmal, J. Takasu, D.M. Shavelle, J.L. Probstfield, A.G. Bertoni, M.J. Budoff, and K.D. O'Brien. 2006. Features of the metabolic syndrome and diabetes mellitus as predictors of aortic valve calcification in the Multi-Ethnic Study of Atherosclerosis. Circulation 113: 2113–2119.PubMedCrossRef
18.
go back to reference Mathieu, P., I. Lemieux, and J.P. Despres. 2010. Obesity, inflammation, and cardiovascular risk. Clinical Pharmacology and Therapeutics 87: 407–416.PubMedCrossRef Mathieu, P., I. Lemieux, and J.P. Despres. 2010. Obesity, inflammation, and cardiovascular risk. Clinical Pharmacology and Therapeutics 87: 407–416.PubMedCrossRef
19.
go back to reference Mathieu, P., P. Poirier, P. Pibarot, I. Lemieux, and J.P. Despres. 2009. Visceral obesity: the link among inflammation, hypertension, and cardiovascular disease. Hypertension 53: 577–584.PubMedCrossRef Mathieu, P., P. Poirier, P. Pibarot, I. Lemieux, and J.P. Despres. 2009. Visceral obesity: the link among inflammation, hypertension, and cardiovascular disease. Hypertension 53: 577–584.PubMedCrossRef
20.
go back to reference Kaden, J.J., R. Kilic, A. Sarikoc, S. Hagl, S. Lang, U. Hoffmann, M. Brueckmann, and M. Borggrefe. 2005. Tumor necrosis factor alpha promotes an osteoblast-like phenotype in human aortic valve myofibroblasts: a potential regulatory mechanism of valvular calcification. International Journal of Molecular Medicine 16: 869–872.PubMed Kaden, J.J., R. Kilic, A. Sarikoc, S. Hagl, S. Lang, U. Hoffmann, M. Brueckmann, and M. Borggrefe. 2005. Tumor necrosis factor alpha promotes an osteoblast-like phenotype in human aortic valve myofibroblasts: a potential regulatory mechanism of valvular calcification. International Journal of Molecular Medicine 16: 869–872.PubMed
21.
go back to reference Bosse, Y., A. Miqdad, D. Fournier, A. Pepin, P. Pibarot, and P. Mathieu. 2009. Refining molecular pathways leading to calcific aortic valve stenosis by studying gene expression profile of normal and calcified stenotic human aortic valves. Circulation. Cardiovascular Genetics 2: 489–498.PubMedCrossRef Bosse, Y., A. Miqdad, D. Fournier, A. Pepin, P. Pibarot, and P. Mathieu. 2009. Refining molecular pathways leading to calcific aortic valve stenosis by studying gene expression profile of normal and calcified stenotic human aortic valves. Circulation. Cardiovascular Genetics 2: 489–498.PubMedCrossRef
22.
go back to reference Derbali, H., Y. Bosse, N. Cote, P. Pibarot, A. Audet, A. Pepin, B. Arsenault, C. Couture, J.P. Despres, and P. Mathieu. 2010. Increased biglycan in aortic valve stenosis leads to the overexpression of phospholipid transfer protein via Toll-like receptor 2. American Journal of Pathology 176: 2638–2645.PubMedCrossRef Derbali, H., Y. Bosse, N. Cote, P. Pibarot, A. Audet, A. Pepin, B. Arsenault, C. Couture, J.P. Despres, and P. Mathieu. 2010. Increased biglycan in aortic valve stenosis leads to the overexpression of phospholipid transfer protein via Toll-like receptor 2. American Journal of Pathology 176: 2638–2645.PubMedCrossRef
Metadata
Title
Inflammation Is Associated with the Remodeling of Calcific Aortic Valve Disease
Authors
Nancy Coté
Ablajan Mahmut
Yohan Bosse
Christian Couture
Sylvain Pagé
Sylvain Trahan
Marie-Chloé Boulanger
Dominique Fournier
Philippe Pibarot
Patrick Mathieu
Publication date
01-06-2013
Publisher
Springer US
Published in
Inflammation / Issue 3/2013
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-012-9579-6

Other articles of this Issue 3/2013

Inflammation 3/2013 Go to the issue