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• W2057671485 abstract "HomeCirculationVol. 114, No. 16Letter by Undas and Jakubowski Regarding Article, “Relationship Between Homocysteine and Mortality in Chronic Kidney Disease” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Undas and Jakubowski Regarding Article, “Relationship Between Homocysteine and Mortality in Chronic Kidney Disease” Anetta Undas, MD, PhD, DSc Hieronim Jakubowski, PhD, DSc Anetta UndasAnetta Undas Institute of Cardiology, Jagiellonian University School of Medicine, Kraków, Poland Search for more papers by this author Hieronim JakubowskiHieronim Jakubowski Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, Newark, NJ, Search for more papers by this author Originally published17 Oct 2006https://doi.org/10.1161/CIRCULATIONAHA.106.634691Circulation. 2006;114:e547To the Editor:We read with keen interest the article by Menon et al,1 which concluded that plasma total homocysteine (tHcy) is not a risk factor for all-cause or cardiovascular disease (CVD) mortality in patients with stage 3 and 4 chronic kidney disease (CKD). The conflicting results of other studies are explained by Menon et al by the failure to adjust for the kidney function.However, a major limitation of this type of study is that it relies on a composite marker, tHcy, that comprises at least 5 different homocysteine species, each of which can exert a distinct biological effect.2 Moreover, tHcy does not encompass other homocysteine metabolites present in human blood.2 Thus, a contribution of specific Hcy-related mechanisms to cardiovascular risk or mortality is likely to be overlooked by using tHcy as a marker. For example, a highly reactive metabolite, Hcy-thiolactone, reacts avidly with proteins to form N-Hcy-protein adducts, which induce an autoimmune response in humans.2N-Hcy-protein adducts occur in human blood2 and are elevated in patients undergoing hemodialysis.3 Elevated levels of anti–N-Hcy-protein autoantibodies, observed in patients with stroke4 and CVD,5 are a common feature of atherosclerosis.2 Moreover, anti–N-Hcy-protein autoantibodies also are associated with C-reactive protein levels.5 Given a high prevalence of elevated tHcy levels in patients with CKD, it might be hypothesized that an autoimmune response against N-Hcy-protein may also play an important role in the pathogenesis of CVD in these subjects.Accumulating evidence suggests that specific homocysteine-mediated mechanisms, including protein modification by Hcy-thiolactone, are implicated in the progression of CVD in subjects with moderate hyperhomocystinemia. If so, tHcy levels may not be the best marker of homocysteine toxicity, at least in some patient groups, such as patients with CKD. It would be more informative to investigate specific markers of homocysteine metabolism both in patients with CKD and in those with normal renal function to elucidate an intricate relation between homocysteine and CVD.DisclosuresNone.1 Menon V, Sarnak MJ, Greene T, Wang X, Pereira AA, Beck GJ, Kusek JW, Selhub J, Collins AJ, Levey AS, Shlipak MG. Relationship between homocysteine and mortality in chronic kidney disease. Circulation. 2006; 113: 1572–1577.LinkGoogle Scholar2 Jakubowski H. Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease. Clin Chem Lab Med. 2005; 43: 1011–1014.MedlineGoogle Scholar3 Perna AF, Satta E, Acanfora F, Lombardi C, Ingrosso D, De Santo NG. Increased plasma protein homocysteinylation in hemodialysis patients. Kidney Int. 2006; 69: 869–876.CrossrefMedlineGoogle Scholar4 Undas A, Perla J, Laciński M, Trzeciak W, Kaźmierski R, Jakubowski H. Autoantibodies against N-homocysteinylated proteins in humans: implications for atherosclerosis. Stroke. 2004; 35: 1299–1304.LinkGoogle Scholar5 Undas A, Jankowski M, Twardowska M, Padjas A, Jakubowski H, Szczeklik A. Autoantibodies to N-homocysteinylated albumin as a marker for early-onset coronary artery disease in men. Thromb Haemost. 2005; 93: 346–350.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Piechocka J, Wrońska M, Chwatko G, Jakubowski H and Głowacki R (2020) Quantification of homocysteine thiolactone in human saliva and urine by gas chromatography-mass spectrometry, Journal of Chromatography B, 10.1016/j.jchromb.2020.122155, 1149, (122155), Online publication date: 1-Jul-2020. Borowczyk K, Piechocka J, Głowacki R, Dhar I, Midtun Ø, Tell G, Ueland P, Nygård O and Jakubowski H (2018) Urinary excretion of homocysteine thiolactone and the risk of acute myocardial infarction in coronary artery disease patients: the WENBIT trial, Journal of Internal Medicine, 10.1111/joim.12834, 285:2, (232-244), Online publication date: 1-Feb-2019. Rajamannan N (2018) Osteocardiology: Calcific Aortic Valve Disease Osteocardiology, 10.1007/978-3-319-64994-8_3, (21-38), . Nachlas A, Li S and Davis M (2017) Developing a Clinically Relevant Tissue Engineered Heart Valve—A Review of Current Approaches, Advanced Healthcare Materials, 10.1002/adhm.201700918, 6:24, (1700918), Online publication date: 1-Dec-2017. Song R, Fullerton D, Ao L, Zheng D, Zhao K and Meng X (2014) BMP-2 and TGF-β1 mediate biglycan-induced pro-osteogenic reprogramming in aortic valve interstitial cells, Journal of Molecular Medicine, 10.1007/s00109-014-1229-z, 93:4, (403-412), Online publication date: 1-Apr-2015. Burnstock G, Ralevic V and Perez D (2013) Purinergic Signaling and Blood Vessels in Health and Disease, Pharmacological Reviews, 10.1124/pr.113.008029, 66:1, (102-192), Online publication date: 1-Jan-2014. Tseng H, Puperi D, Kim E, Ayoub S, Shah J, Cuchiara M, West J and Grande-Allen K (2014) Anisotropic Poly(Ethylene Glycol)/Polycaprolactone Hydrogel–Fiber Composites for Heart Valve Tissue Engineering, Tissue Engineering Part A, 10.1089/ten.tea.2013.0397, 20:19-20, (2634-2645), Online publication date: 1-Oct-2014. Rajamannan N and Johnson C (2014) Calcific Aortic Valve Disease: The Role of the Stem Cell Niche Molecular Biology of Valvular Heart Disease, 10.1007/978-1-4471-6350-3_1, (1-12), . Sucosky P (2014) Hemodynamic Mechanisms of Bicuspid Aortic Valve Calcification and Aortopathy Molecular Biology of Valvular Heart Disease, 10.1007/978-1-4471-6350-3_11, (81-94), . Akerström F, Barderas M and Rodríguez-Padial L (2014) Aortic stenosis: a general overview of clinical, pathophysiological and therapeutic aspects, Expert Review of Cardiovascular Therapy, 10.1586/erc.12.171, 11:2, (239-250), Online publication date: 1-Feb-2013. Jakubowski H (2013) An Overview of Homocysteine Metabolism Homocysteine in Protein Structure/Function and Human Disease, 10.1007/978-3-7091-1410-0_2, (7-18), . Hakuno D, Kimura N, Yoshioka M and Fukuda K (2011) Role of Angiogenetic Factors in Cardiac Valve Homeostasis and Disease, Journal of Cardiovascular Translational Research, 10.1007/s12265-011-9317-8, 4:6, (727-740), Online publication date: 1-Dec-2011. Bischoff J and Aikawa E (2011) Progenitor Cells Confer Plasticity to Cardiac Valve Endothelium, Journal of Cardiovascular Translational Research, 10.1007/s12265-011-9312-0, 4:6, (710-719), Online publication date: 1-Dec-2011. Chester A (2011) Molecular and cellular mechanisms of valve calcification, Aswan Heart Centre Science & Practice Series, 10.5339/ahcsps.2011.4, 2011:1, Online publication date: 14-Apr-2011. (2011) , Nihon Toseki Igakkai Zasshi, 10.4009/jsdt.44.389, 44:5, (389-391), . Syväranta S, Helske S, Laine M, Lappalainen J, Kupari M, Mäyränpää M, Lindstedt K and Kovanen P (2010) Vascular Endothelial Growth Factor–Secreting Mast Cells and Myofibroblasts, Arteriosclerosis, Thrombosis, and Vascular Biology, 30:6, (1220-1227), Online publication date: 1-Jun-2010. 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. Rajamannan N (2008) Calcific Aortic Stenosis, Arteriosclerosis, Thrombosis, and Vascular Biology, 29:2, (162-168), Online publication date: 1-Feb-2009.Sucosky P, Balachandran K, Elhammali A, Jo H and Yoganathan A (2008) Altered Shear Stress Stimulates Upregulation of Endothelial VCAM-1 and ICAM-1 in a BMP-4– and TGF-β1–Dependent Pathway, Arteriosclerosis, Thrombosis, and Vascular Biology, 29:2, (254-260), Online publication date: 1-Feb-2009.Monzack E, Gu X and Masters K (2008) Efficacy of Simvastatin Treatment of Valvular Interstitial Cells Varies With the Extracellular Environment, Arteriosclerosis, Thrombosis, and Vascular Biology, 29:2, (246-253), Online publication date: 1-Feb-2009.Yip C, Chen J, Zhao R and Simmons C (2009) Calcification by Valve Interstitial Cells Is Regulated by the Stiffness of the Extracellular Matrix, Arteriosclerosis, Thrombosis, and Vascular Biology, 29:6, (936-942), Online publication date: 1-Jun-2009.Benton J, Kern H, Leinwand L, Mariner P and Anseth K (2009) Statins Block Calcific Nodule Formation of Valvular Interstitial Cells by Inhibiting α-Smooth Muscle Actin Expression, Arteriosclerosis, Thrombosis, and Vascular Biology, 29:11, (1950-1957), Online publication date: 1-Nov-2009. Chakraborty S, Cheek J, Sakthivel B, Aronow B and Yutzey K (2008) Shared gene expression profiles in developing heart valves and osteoblast progenitor cells, Physiological Genomics, 10.1152/physiolgenomics.90212.2008, 35:1, (75-85), Online publication date: 1-Sep-2008. Meng X, Ao L, Song Y, Babu A, Yang X, Wang M, Weyant M, Dinarello C, Cleveland J and Fullerton D (2008) Expression of functional Toll-like receptors 2 and 4 in human aortic valve interstitial cells: potential roles in aortic valve inflammation and stenosis, American Journal of Physiology-Cell Physiology, 10.1152/ajpcell.00137.2007, 294:1, (C29-C35), Online publication date: 1-Jan-2008. Tziomalos K, Athyros V, Karagiannis A and Mikhailidis D (2008) Established and emerging vascular risk factors and the development of aortic stenosis: an opportunity for prevention?, Expert Opinion on Therapeutic Targets, 10.1517/14728222.12.7.809, 12:7, (809-820), Online publication date: 1-Jul-2008. Osman L, Chester A, Sarathchandra P, Latif N, Meng W, Taylor P and Yacoub M (2007) A Novel Role of the Sympatho-Adrenergic System in Regulating Valve Calcification, Circulation, 10.1161/CIRCULATIONAHA.106.681072, 116:11_supplement, Online publication date: 11-Sep-2007. Jakubowski H The molecular basis of homocysteine thiolactone-mediated vascular disease, Clinical Chemical Laboratory Medicine, 10.1515/CCLM.2007.338, 45:12 Godby R, Munjal C, Opoka A, Smith J, Yutzey K, Narmoneva D and Hinton R (2014) Cross Talk between NOTCH Signaling and Biomechanics in Human Aortic Valve Disease Pathogenesis, Journal of Cardiovascular Development and Disease, 10.3390/jcdd1030237, 1:3, (237-256) October 17, 2006Vol 114, Issue 16 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.106.634691PMID: 17043173 Originally publishedOctober 17, 2006 PDF download Advertisement SubjectsEpidemiology" @default.
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