Cholesterol in Vascular and Valvular Calcification
2001; Lippincott Williams & Wilkins; Volume: 104; Issue: 16 Linguagem: Inglês
10.1161/circ.104.16.1881
ISSN1524-4539
Autores Tópico(s)Cardiac Valve Diseases and Treatments
ResumoHomeCirculationVol. 104, No. 16Cholesterol in Vascular and Valvular Calcification Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBCholesterol in Vascular and Valvular Calcification Linda L. Demer, MD, PhD Linda L. DemerLinda L. Demer From the Departments of Medicine and Physiology, UCLA School of Medicine, Los Angeles, Calif. Originally published16 Oct 2001https://doi.org/10.1161/circ.104.16.1881Circulation. 2001;104:1881–1883In the early 1990s, the late Jeff Hoeg had the foresight to ask whether vascular calcification relates to the duration and severity of exposure to cholesterol. In a group of homozygous hyperlipidemic patients for whom detailed records of cholesterol levels were available over a long period of time, he and his colleagues found that coronary calcification scores by ultrafast computed tomographic scanning correlated significantly with the cholesterol year product.1 Studies that lack long-term cholesterol history may miss a correlation between lipids and calcification, because current treatments so dramatically change cholesterol levels as to make them unrepresentative of long-term exposure.See p 1927In the present issue of Circulation, Pohle et al2 successfully overcame these difficulties by studying the rate of change in calcification as a function of change in lipid levels, excluding patients in whom treatment was altered during the study period. These investigators found that both coronary calcification and aortic valve calcification progress more rapidly in subjects with levels of LDL >130 mg/dL. This finding dovetails with those of Callister et al,3 who discovered that patients who successfully lowered their cholesterol levels with lipid-lowering agents significantly reduced the progression of coronary calcification. In a large population of young subjects, the risk factor that correlated most significantly with coronary calcification was LDL cholesterol.4 This relation was stronger than the correlation with age, smoking, fasting insulin, blood pressure, or male sex.4 In another study of asymptomatic outpatients, LDL cholesterol was the only risk factor correlating with progression of coronary calcification by electron-beam computed tomography over an 18-month period.5The correlation of LDL cholesterol exposure to valvular and vascular calcification raises the possibility of a mechanistic role, which is also supported by in vitro studies. Two groups showed that lipid elements in atherosclerotic plaque may serve as the nidus for mineralization, as they do in bone.6,7 In addition, in vitro studies have shown that the artery wall contains cells capable of osteoblastic differentiation and mineralization.8–10 Further studies have shown that osteogenesis in these cells is induced by oxidized lipids.11 Although the source of these cells has not been established, the presence of heterogeneous subpopulations in the media has long been proposed by Julie and Gordon Campbell and colleagues, and the possibility that calcifying valvular or vascular cells derive from circulating precursor cells is supported by their recent demonstration that marrow stromal-derived cells are present in atherosclerotic neointima.12Heart valve calcification has received less research attention than artery wall calcification. Textbooks have distinguished calcific and atherosclerotic aortic stenosis as 2 separate diseases. The calcific form has been attributed to degeneration or "wear-and-tear," a factor that was thought to contribute to a variety of diseases until adequate research identified their true causes. Ongoing research now suggests that it is time to replace the old view on aortic stenosis.Calcific aortic stenosis may simply represent a later stage or one end of the spectrum of atherosclerotic disease, as calcified plaque does in the artery wall. As with vascular calcification, calcification in cardiac valves is now known to have many features of bone formation. The degree and location of valvular calcification closely corresponds with mRNA expression of osteopontin, a protein regulating biomineralization.13 Feldman et al14 described ossification in human aortic valve specimens. In a more systematic examination of ≈350 human aortic valves removed for replacement surgery, Mohler et al15 found that most were calcified and that ≈15% contained fully-formed, lamellar or endochondral bone tissue with hematopoietic marrow and evidence of remodeling. Specimens containing bone tissue also showed expression of the potent osteogenic factors bone morphogenetic protein (BMP)-2 and BMP-4.In vitro studies of cardiac valve cells have also revealed similarities with in vitro vascular calcification. Mohler' group also harvested cells from the aortic valves of humans and dogs. They identified and characterized a subpopulation of mesenchymal cells from the interstitial cell population that were able to produce nodules containing hydroxyapatite-mineralized matrix in vitro. These nodules were essentially identical to the calcifying vascular cells that were previously isolated from the aortic media,7 and they were induced to mineralize by the same factors: TGF-β, 25-hydroxycholesterol, and BMP-2.A unique feature of cardiac valve tissue, the lack of conventional smooth muscle cells, provides a clue about the origin of calcifying valvular cells. Although some α-smooth muscle actin has been observed in diseased valves, in general, only endothelial, fibroblastic, and interstitial cells are considered normal constituents. This would support the concept that calcifying valvular cells are not dedifferentiated or redifferentiated smooth muscle cells. Whatever the origin, whether embryonic remnant, blood-borne precursor, or local mesenchymal tissue, Mohler' mesenchymal cells in valves may be the same cells as calcifying vascular cells in the artery wall.As with artery wall calcification, lipids may also contribute to valvular calcification. Cholesterol concentration is significantly higher in patients with calcific aortic stenosis than in control subjects.16 In bioprosthetic valves, eliminating lipids from the biological matrix by ethanol extraction prevents in vivo calcification.17 Bioprosthetic valves raise an interesting question. They are considered free of viable cells after glutaraldehyde fixation. Nevertheless, they undergo mineralization, suggesting that valvular calcification may be cell-independent and passive. However, it is possible that the cell-produced matrix and/or its fixative-modified proteins have the proper physical characteristics to serve as crystallization foci. Thus, the regulated aspect of mineralization, cellular production of a mineral-competent matrix, may have already been completed. Another possibility is that cells migrate into or deposit on the bioprosthetic valves. Recent studies from a variety of laboratories indicate that circulating blood contains immature mesenchymal cells capable of differentiation into endothelial, smooth muscle, and other lineages, presumably from the marrow stromal cell population,18 much the same way as hematopoietic stem cells are present in peripheral blood and are capable of incorporating themselves into tissue. If cells can deposit themselves onto devitalized bioprosthetic valve tissue and deposit appropriate matrix, then cellular-regulated mineralization may take place.One consequence of the fact that vascular calcification resembles osteogenesis deep within the artery wall is that infusions capable of dissolving the calcium mineral that forms within matrix in vascular tissue should be equally capable of dissolving the calcium mineral that forms within skeletal bone. Newly forming bone in the skeleton is located immediately adjacent to the subendothelial space of the Haversian canals and marrow, only a few cell thicknesses from the blood lumen. Because atherosclerotic calcification is usually much deeper, skeletal calcification may be more likely to be removed by intravenous chelators than atherosclerotic calcification.Some evidence raises concerns that warfarin has a role in cardiovascular calcification. The small protein matrix GLA protein (MGP) is thought to serve as an inhibitor of soft-tissue calcification, possibly through inhibitory interaction with BMP-2.19 GLA proteins, which include coagulation cascade factors, are unusual in having post-translational carboxylation of certain glutamic acid residues, a modification thought to be important for function. The carboxylase responsible for this modification depends on vitamin K. Because warfarin interferes with vitamin K–dependent enzymes, it is theoretically possible that warfarin treatment or dietary vitamin K deficiency may increase the risk of vascular calcification by reducing the mineral-inhibitory activity of MGP.It has been suggested that calcification does not increase the risk of plaque rupture because it does not weaken the plaque' resistance to hoop stresses. If anything, calcification should increase resistance to circumferential hoop stresses. However, instability is expected to be induced by calcium deposits through dramatically increased solid shear stresses along the sharp interface where the pulsating, compliant soft tissue meets mineral. This interface is the known site of plaque rupture during balloon angioplasty.20With aging, soft tissues harden and hard tissues soften. One explanation may be that both processes are stages of last resort in chronic inflammatory responses to various stimuli, including oxidized lipids or autoimmune phenomena. Chronic inflammation may have evolved from mechanisms protecting against microorganisms and even macroorganisms such as helminths. The last resort of immune defense in soft tissue is to wall off the invader with a bone barrier. The amorphous calcium mineral may simply be the first stage in osteogenesis. In hard tissue infection, the anchorage-dependent microorganisms thrive in mineral matrix, and the defense of last resort is to eliminate that anchorage by dissolving the mineral matrix. This process is known as inflammatory osteolysis.It is optimistic to conclude, on the basis of this study' correlation, that cholesterol lowering may prevent or reverse valvular calcification. Drawing treatment conclusions from correlations may oblige us to send coronary patients to plastic surgeons for the correction of ear lobe creases. However, the findings of Pohle et al2 warrant aggressive investigation of a causative relation between cholesterol and cardiovascular calcification.The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.FootnotesCorrespondence to Linda L. Demer, MD, PhD, Maud Cady Guthman Professor of Medicine and Physiology, Vice Chair, Department of Medicine, UCLA School of Medicine, Mail Box 951679, Los Angeles, CA 90095-1679. References 1 Hoeg JM, Feuerstein IM, Tucker EE. Detection and quantitation of calcific atherosclerosis by ultrafast computed tomography in children and young adults with homozygous familial hypercholesterolemia. Arterioscler Thromb. 1994; 14: 1066–1074.CrossrefMedlineGoogle Scholar2 Pohle K, Mäffert R, Ropers D, et al. Progression of aortic valve calcification: association with coronary atherosclerosis and cardiovascular risk factors. Circulation. 2001; 104: 1927–1932.CrossrefMedlineGoogle Scholar3 Callister TQ, Raggi P, Cooli B, et al. Effect of HMG-CoA reductase inhibitors on coronary artery disease as assessed by electron-beam computed tomography. N Engl J Med. 1998; 339: 1972–1978.CrossrefMedlineGoogle Scholar4 Bild DE, Folsom AR, Lowe LP, et al. Prevalence and correlates of coronary calcification in black and white young adults: the coronary artery risk development in young adults (CARDIA) study. Arteroscler Thromb Vasc Biol. 2001; 21: 852–857.CrossrefMedlineGoogle Scholar5 Schmermund A, Baumgart D, Mohlenkamp S, et al. Natural history and topographic pattern of progression of coronary calcification in symptomatic patients: an electron-beam CT study. Arterioscler Thromb Vasc Biol. 2001, 21: 421–426.CrossrefMedlineGoogle Scholar6 Sarig S, Weiss TA, Katz I, et al. Detection of cholesterol associated with calcium mineral using confocal fluorescence microscopy. Lab Invest. 1994; 71: 782–787.MedlineGoogle Scholar7 Tanimura A, McGregor DH, Anderson HC. Calcification in atherosclerosis, I: human studies. J Exp Pathol. 1986; 2: 261–273.MedlineGoogle Scholar8 Bostrom K, Watson KE, Horn S, et al. Bone morphogenetic protein expression in human atherosclerotic lesions. J Clin Invest. 1993; 91: 1800–1809.CrossrefMedlineGoogle Scholar9 Shanahan CM, Cary NR, Salisbury JR, et al. Medial localization of mineralization-regulating proteins in association with Monckeberg' sclerosis: evidence for smooth muscle cell-mediated vascular calcification. Circulation. 1999; 100: 2168–2176.CrossrefMedlineGoogle Scholar10 Shioi A, Nishizawa Y, Jono S, et al. β-Glycerophosphate accelerates calcification in cultured bovine vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 1995; 15: 2003–2009.CrossrefMedlineGoogle Scholar11 Parhami F, Morrow AD, Balucan J, et al. Lipid oxidation products have opposite effects on calcifying vascular cell and bone cell differentiation: a possible explanation for the paradox of arterial calcification in osteoporotic patients. Arterioscler Thromb Vasc Biol. 1997; 17: 680–687.CrossrefMedlineGoogle Scholar12 Han CI, Campbell GR, Campbell JH. Circulating bone marrow cells can contribute to neointimal formation. J Vasc Res. 2001; 38: 113–119.CrossrefMedlineGoogle Scholar13 O"Brien KD, Kuusisto J, Reichenbach DD, et al. Osteopontin is expressed in human aortic valvular lesions. Circulation. 1995; 92: 2163–2168.CrossrefMedlineGoogle Scholar14 Feldman T, Glagov S, Carroll JD. Restenosis following successful balloon valvuloplasty: bone formation in aortic valve leaflets. Cathet Cardiovasc Diagn. 1993; 29: 1–7.CrossrefMedlineGoogle Scholar15 Mohler ER3rd, Chawla MK, Chang AW, et al. Identification and characterization of calcifying valve cells from human and canine aortic valves. J Heart Valve Dis. 1999; 8: 254–260.MedlineGoogle Scholar16 Chui MC, Newby DE, Panarelli M, et al. Association between calcific aortic stenosis and hypercholesterolemia: is there a need for a randomized controlled trial of cholesterol-lowering therapy? Clin Cardiol. 2001; 24: 52–55.CrossrefMedlineGoogle Scholar17 Vyavahare NR, Jones PL, Hirsch D, et al. Prevention of glutaraldehyde-fixed bioprosthetic heart valve calcification by alcohol pretreatment: further mechanistic studies. J Heart Valve Dis. 2000; 9: 561–566.MedlineGoogle Scholar18 Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 1997; 276: 71–74.CrossrefMedlineGoogle Scholar19 Bostrom K, Tsao D, Shen S, et al. Matrix Gla protein modulates differentiation induced by bone morphogenetic protein-2 in C3H10T1/2 cells. J Biol Chem. 2001; 276: 14044–14052.CrossrefMedlineGoogle Scholar20 Fitzgerald PJ, Ports TA, Yock PG. Contribution of localized calcium deposits to dissection after angioplasty: an observational study using intravascular ultrasound. Circulation. 1992; 86: 64–70.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Vidavsky N, Kunitake J and Estroff L (2020) Multiple Pathways for Pathological Calcification in the Human Body, Advanced Healthcare Materials, 10.1002/adhm.202001271, 10:4, (2001271), Online publication date: 1-Feb-2021. Singh A, Tandon S and Tandon C (2021) An update on vascular calcification and potential therapeutics, Molecular Biology Reports, 10.1007/s11033-020-06086-y, 48:1, (887-896), Online publication date: 1-Jan-2021. Zhou Y, Hellberg M, Hellmark T, Höglund P and Clyne N (2020) Twelve months of exercise training did not halt abdominal aortic calcification in patients with CKD – a sub-study of RENEXC-a randomized controlled trial, BMC Nephrology, 10.1186/s12882-020-01881-y, 21:1, Online publication date: 1-Dec-2020. Schantl A, Verhulst A, Neven E, Behets G, D'Haese P, Maillard M, Mordasini D, Phan O, Burnier M, Spaggiari D, Decosterd L, MacAskill M, Alcaide-Corral C, Tavares A, Newby D, Beindl V, Maj R, Labarre A, Hegde C, Castagner B, Ivarsson M and Leroux J (2020) Inhibition of vascular calcification by inositol phosphates derivatized with ethylene glycol oligomers, Nature Communications, 10.1038/s41467-019-14091-4, 11:1, Online publication date: 1-Dec-2020. Dai L, Debowska M, Lukaszuk T, Bobrowski L, Barany P, Söderberg M, Thiagarajan D, Frostegård J, Wennberg L, Lindholm B, Qureshi A, Waniewski J and Stenvinkel P (2020) Phenotypic features of vascular calcification in chronic kidney disease, Journal of Internal Medicine, 10.1111/joim.13012, 287:4, (422-434), Online publication date: 1-Apr-2020. Jing J, Chen X, Meng Z, Su W, Liu Y, Zhang Y, Zhu H, Yao W and Fu T (2020) Two-Dimensional Immiscible Domain of Cholesterol in the Lipid Bilayer Membrane Promotes Early Stage Calcification by Inducing Oriented Nucleation of Hydroxyapatite, Langmuir, 10.1021/acs.langmuir.9b03489, 36:8, (2136-2142), Online publication date: 3-Mar-2020. Feig M, Pop C, Bhardwaj G, Sappa P, Dörr M, Ameling S, Weitmann K, Nauck M, Lehnert K, Beug D, Kühl U, Schultheiss H, Völker U, Felix S and Hammer E (2019) Global plasma protein profiling reveals DCM characteristic protein signatures, Journal of Proteomics, 10.1016/j.jprot.2019.103508, 209, (103508), Online publication date: 1-Oct-2019. Lee S, Kim D, Youn Y, Joo H, Yoo K and Lee S (2019) Rosuvastatin attenuates bioprosthetic heart valve calcification, The Journal of Thoracic and Cardiovascular Surgery, 10.1016/j.jtcvs.2018.12.042, 158:3, (731-741.e1), Online publication date: 1-Sep-2019. Schantl A, Ivarsson M and Leroux J (2018) Investigational Pharmacological Treatments for Vascular Calcification, Advanced Therapeutics, 10.1002/adtp.201800094, 2:1, (1800094), Online publication date: 1-Jan-2019. Riad A, Narasimhulu C, Deme P and Parthasarathy S (2018) A Novel Mechanism for Atherosclerotic Calcification: Potential Resolution of the Oxidation Paradox, Antioxidants & Redox Signaling, 10.1089/ars.2017.7362, 29:5, (471-483), Online publication date: 10-Aug-2018. Williams M, Sugatani T, Agapova O, Fang Y, Gaut J, Faugere M, Malluche H and Hruska K (2018) The activin receptor is stimulated in the skeleton, vasculature, heart, and kidney during chronic kidney disease, Kidney International, 10.1016/j.kint.2017.06.016, 93:1, (147-158), Online publication date: 1-Jan-2018. Rajamannan N (2018) Osteocardiology: Calcific Aortic Valve Disease Osteocardiology, 10.1007/978-3-319-64994-8_3, (21-38), . Perrotta I and Perri E (2017) Ultrastructural, Elemental and Mineralogical Analysis of Vascular Calcification in Atherosclerosis, Microscopy and Microanalysis, 10.1017/S1431927617012533, 23:5, (1030-1039), Online publication date: 1-Oct-2017. Lee S, Kim D, Youn Y, Lee S, Joo H, Chang B and Yoo K (2017) Effect of Rosuvastatin on Bovine Pericardial Aortic Tissue Valve Calcification in a Rat Subdermal Implantation Model, Korean Circulation Journal, 10.4070/kcj.2016.0214, 47:3, (401), . Harper E, Forde H, Davenport C, Rochfort K, Smith D and Cummins P (2016) Vascular calcification in type-2 diabetes and cardiovascular disease: Integrative roles for OPG, RANKL and TRAIL, Vascular Pharmacology, 10.1016/j.vph.2016.02.003, 82, (30-40), Online publication date: 1-Jul-2016. Nomura Y, Chu K, Gardecki J, Sun C, Liu L, Martinez-Martinez E, Aikawa E and Tearney G (2015) Innovations in Microscopic Imaging of Atherosclerosis and Valvular Disease Cardiovascular Imaging, 10.1007/978-3-319-09268-3_12, (251-265), . Schmidt N, Brandsch C, Schutkowski A, Hirche F and Stangl G (2014) Dietary Vitamin D Inadequacy Accelerates Calcification and Osteoblast-Like Cell Formation in the Vascular System of LDL Receptor Knockout and Wild-Type Mice, The Journal of Nutrition, 10.3945/jn.113.189118, 144:5, (638-646), Online publication date: 1-May-2014. Ferreira-González I, Pinar-Sopena J, Ribera A, Marsal J, Cascant P, González-Alujas T, Evangelista A, Brotons C, Moral I, Permanyer-Miralda G, García-Dorado D and Tornos P (2012) Prevalence of calcific aortic valve disease in the elderly and associated risk factors: a population-based study in a Mediterranean area, European Journal of Preventive Cardiology, 10.1177/2047487312451238, 20:6, (1022-1030), Online publication date: 1-Dec-2013. Cheng C, Chang H, Huang P, Chu Y and Lin S (2013) Composition and Distribution of Elements and Ultrastructural Topography of a Human Cardiac Calculus, Biological Trace Element Research, 10.1007/s12011-013-9603-1, 152:1, (143-151), Online publication date: 1-Apr-2013. Liakopoulos O, Kuhn E, Choi Y and Wahlers T (2012) Aktuelle Evidenz einer Statintherapie in der HerzchirurgieCurrent evidence for statin therapy in cardiac surgery, Zeitschrift für Herz-,Thorax- und Gefäßchirurgie, 10.1007/s00398-012-0947-1, 26:6, (394-400), Online publication date: 1-Dec-2012. Schumm J, Luetzkendorf S, Rademacher W, Franz M, Schmidt-Winter C, Kiehntopf M, Figulla H and Brehm B (2011) In patients with aortic stenosis increased flow-mediated dilation is independently associated with higher peak jet velocity and lower asymmetric dimethylarginine levels, American Heart Journal, 10.1016/j.ahj.2011.02.015, 161:5, (893-899), Online publication date: 1-May-2011. Davidson M, Beam C, Haffner S, Perez A, D'Agostino R and Mazzone T (2010) Pioglitazone Versus Glimepiride on Coronary Artery Calcium Progression in Patients With Type 2 Diabetes Mellitus, Arteriosclerosis, Thrombosis, and Vascular Biology, 30:9, (1873-1876), Online publication date: 1-Sep-2010. Gassler N and Schnabel P (2010) Pathology of Aortic Stenosis Cardiovascular Interventions in Clinical Practice, 10.1002/9781444316704.ch7, (71-85) Rajamannan N (2010) Mechanisms of aortic valve calcification: the LDL-density-radius theory: a translation from cell signaling to physiology, American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.00824.2009, 298:1, (H5-H15), Online publication date: 1-Jan-2010. Yetkin E and Waltenberger J (2009) Molecular and cellular mechanisms of aortic stenosis, International Journal of Cardiology, 10.1016/j.ijcard.2009.03.108, 135:1, (4-13), Online publication date: 1-Jun-2009. Rajamannan N (2008) Calcific Aortic Stenosis, Arteriosclerosis, Thrombosis, and Vascular Biology, 29:2, (162-168), Online publication date: 1-Feb-2009. Rajamannan N (2009) Cellular, Molecular, and Genetic Mechanisms of Valvular Heart Disease Valvular Heart Disease: A Companion to Braunwald's Heart Disease, 10.1016/B978-1-4160-5892-2.00003-9, (39-54), . Helske S, Kupari M, Lindstedt K and Kovanen P (2007) Aortic valve stenosis: an active atheroinflammatory process, Current Opinion in Lipidology, 10.1097/MOL.0b013e3282a66099, 18:5, (483-491), Online publication date: 1-Oct-2007. Zeng Z, Nievelstein-Post P, Yin Y, Jan K, Frank J and Rumschitzki D (2007) Macromolecular transport in heart valves. III. Experiment and theory for the size distribution of extracellular liposomes in hyperlipidemic rabbits, American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.00606.2006, 292:6, (H2687-H2697), Online publication date: 1-Jun-2007. Arishiro K, Hoshiga M, Negoro N, Jin D, Takai S, Miyazaki M, Ishihara T and Hanafusa T (2007) Angiotensin Receptor-1 Blocker Inhibits Atherosclerotic Changes and Endothelial Disruption of the Aortic Valve in Hypercholesterolemic Rabbits, Journal of the American College of Cardiology, 10.1016/j.jacc.2006.11.043, 49:13, (1482-1489), Online publication date: 1-Apr-2007. Rajamannan N (2007) Reassessment of statins to retard the progression of aortic stenosis, Current Cardiology Reports, 10.1007/BF02938335, 9:2, (99-104), Online publication date: 1-Apr-2007. Aikawa E, Nahrendorf M, Sosnovik D, Lok V, Jaffer F, Aikawa M and Weissleder R (2007) Multimodality Molecular Imaging Identifies Proteolytic and Osteogenic Activities in Early Aortic Valve Disease, Circulation, 115:3, (377-386), Online publication date: 23-Jan-2007.Aboulhosn J and Child J (2006) Left Ventricular Outflow Obstruction, Circulation, 114:22, (2412-2422), Online publication date: 28-Nov-2006. Jayalath R, Mangan S and Golledge J (2005) Aortic Calcification, European Journal of Vascular and Endovascular Surgery, 10.1016/j.ejvs.2005.04.030, 30:5, (476-488), Online publication date: 1-Nov-2005. Rashidi A, Adler D, Casscells W and Madjid M (2005) Is it time to prescribe statins to patients with calcified aortic stenosis?, American Heart Journal, 10.1016/j.ahj.2005.01.021, 150:1, (41-45), Online publication date: 1-Jul-2005. Adler Y, Fisman E, Shemesh J, Tanne D, Hovav B, Motro M, Schwammenthal E and Tenenbaum A (2005) Usefulness of helical computed tomography in detection of mitral annular calcification as a marker of coronary artery disease, International Journal of Cardiology, 10.1016/j.ijcard.2004.03.044, 101:3, (371-376), Online publication date: 1-Jun-2005. Wu B, Elmariah S, Kaplan F, Cheng G and Mohler E (2004) Paradoxical Effects of Statins on Aortic Valve Myofibroblasts and Osteoblasts, Arteriosclerosis, Thrombosis, and Vascular Biology, 25:3, (592-597), Online publication date: 1-Mar-2005. Mohler E (2004) Mechanisms of aortic valve calcification, The American Journal of Cardiology, 10.1016/j.amjcard.2004.08.013, 94:11, (1396-1402), Online publication date: 1-Dec-2004. Kizu A, Shioi A, Jono S, Koyama H, Okuno Y and Nishizawa Y (2004) Statins inhibit in vitro calcification of human vascular smooth muscle cells induced by inflammatory mediators, Journal of Cellular Biochemistry, 10.1002/jcb.20207, 93:5, (1011-1019), Online publication date: 1-Dec-2004. Hsu H and Abbo B (2004) Role of bicarbonate/CO2 buffer in the initiation of vesicle-mediated calcification: mechanisms of aortic calcification related to atherosclerosis, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 10.1016/j.bbadis.2004.06.001, 1690:2, (118-123), Online publication date: 1-Oct-2004. Agmon Y, Khandheria B, Jamil Tajik A, Seward J, Sicks J, Fought A, Michael O'Fallon W, Smith T, Wiebers D and Meissner I (2004) Inflammation, infection, and aortic valve sclerosis, Atherosclerosis, 10.1016/j.atherosclerosis.2004.01.028, 174:2, (337-342), Online publication date: 1-Jun-2004. Farivar R and Cohn L (2003) Hypercholesterolemia is a risk factor for bioprosthetic valve calcification and explantation, The Journal of Thoracic and Cardiovascular Surgery, 10.1016/S0022-5223(03)00708-6, 126:4, (969-975), Online publication date: 1-Oct-2003. Wong N, Sciammarella M, Arad Y, Miranda-Peats R, Polk D, Hachamovich R, Friedman J, Hayes S, Daniell A and Berman D (2003) Relation of thoracic aortic and aortic valve calcium to coronary artery calcium and risk assessment, The American Journal of Cardiology, 10.1016/S0002-9149(03)00976-7, 92:8, (951-955), Online publication date: 1-Oct-2003. Bashore T and Gardner T (2003) Valvular heart disease, Journal of the American College of Cardiology, 10.1016/S0735-1097(03)00675-2, 42:2, (388-390), Online publication date: 1-Jul-2003. Dutta R, Singh U, Li T, Fornage M and Teng B (2003) Hepatic gene expression profiling reveals perturbed calcium signaling in a mouse model lacking both LDL receptor and Apobec1 genes, Atherosclerosis, 10.1016/S0021-9150(03)00133-3, 169:1, (51-62), Online publication date: 1-Jul-2003. Bidder M, Shao J, Charlton-Kachigian N, Loewy A, Semenkovich C and Towler D (2002) Osteopontin Transcription in Aortic Vascular Smooth Muscle Cells Is Controlled by Glucose-regulated Upstream Stimulatory Factor and Activator Protein-1 Activities, Journal of Biological Chemistry, 10.1074/jbc.M206235200, 277:46, (44485-44496), Online publication date: 1-Nov-2002. October 16, 2001Vol 104, Issue 16 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.104.16.1881PMID: 11602487 Originally publishedOctober 16, 2001 KeywordsatherosclerosisEditorialscalciumlipidsPDF download Advertisement
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