{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T13:38:54Z","timestamp":1762004334291},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2011,5,16]],"date-time":"2011-05-16T00:00:00Z","timestamp":1305504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Vitamin D deficiency has been linked to hypertension and an increased prevalence of cardiovascular risk factors and disease. Studies in vitamin D receptor knockout (VDR KO) mice revealed an overstimulated renin-angiotensin system (RAS) and consequent high blood pressure and cardiac hypertrophy. VDR KO mice correspond phenotypically and metabolically to humans with hereditary 1,25-dihydroxyvitamin D\u2013resistant rickets (HVDRR). There are no data on the cardiovascular system in human HVDRR. To better understand the effects of vitamin D on the human cardiovascular system, the RAS, blood pressure levels, and cardiac structures were examined in HVDRR patients. Seventeen patients (9 males, 8 females, aged 6 to 36 years) with hereditary HVDRR were enrolled. The control group included age- and gender-matched healthy subjects. Serum calcium, phosphorous, creatinine, 25-hydroxyvitamin D [25(OH)D],1,25-dihydroxyvitamin D3 [1,25(OH)2D3], parathyroid hormone (PTH), plasma rennin activity (PRA), aldosterone, angiotensin II (AT-II), and angiotensin-converting enzyme (ACE) levels were determined. Ambulatory 24-hour blood pressure measurements and echocardiographic examinations were performed. Serum calcium, phosphorus, and alkaline phosphatase values were normal. Serum 1,25(OH)2D3 and PTH but not PRA and ACE levels were elevated in the HVDRR patients. AT-II levels were higher than normal in the HVDRR patients but not significantly different from those of the controls. Aldosterone levels were normal in all HVDRR patients. No HVDRR patient had hypertension or echocardiographic pathology. These findings reveal that 6- to 36-year-old humans with HVDRR have normal renin and ACE activity, mild but nonsignificant elevation of AT-II, normal aldosterone levels, and no hypertension or gross heart abnormalities. \u00a9 2011 American Society for Bone and Mineral Research<\/jats:p>","DOI":"10.1002\/jbmr.431","type":"journal-article","created":{"date-parts":[[2011,5,16]],"date-time":"2011-05-16T16:14:53Z","timestamp":1305562493000},"page":"2252-2260","source":"Crossref","is-referenced-by-count":38,"title":["The renin-angiotensin system, blood pressure, and heart structure in patients with hereditary vitamin D\u2013resistance rickets (HVDRR)"],"prefix":"10.1093","volume":"26","author":[{"given":"Dov","family":"Tiosano","sequence":"first","affiliation":[{"name":"The Rappaport Faculty of Medicine, The Technion\u2013Israel Institute of Technology, Haifa, Israel"},{"name":"Division of Pediatric Endocrinology, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yitzchak","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Institute of Pediatric Cardiology and Adults with Congenital Heart Disease, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulia","family":"Braver","sequence":"additional","affiliation":[{"name":"Institute of Pediatric Cardiology and Adults with Congenital Heart Disease, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir","family":"Hadash","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vardit","family":"Gepstein","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosef","family":"Weisman","sequence":"additional","affiliation":[{"name":"Bone Disease Unit, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avraham","family":"Lorber","sequence":"additional","affiliation":[{"name":"The Rappaport Faculty of Medicine, The Technion\u2013Israel Institute of Technology, Haifa, Israel"},{"name":"Institute of Pediatric Cardiology and Adults with Congenital Heart Disease, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,5,16]]},"reference":[{"key":"2024020317581080900_bib1","doi-asserted-by":"crossref","first-page":"3927","DOI":"10.1210\/jc.2008-0784","article-title":"Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography","volume":"93","author":"Pilz","year":"2008","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020317581080900_bib2","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/nrcardio.2009.135","article-title":"Vitamin D status and arterial hypertension: a systematic review","volume":"6","author":"Pilz","year":"2009","journal-title":"Nat Rev Cardiol."},{"key":"2024020317581080900_bib3","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1161\/HYPERTENSIONAHA.108.119602","article-title":"Expression of the vitamin D receptor is increased in the hypertrophic heart","volume":"52","author":"Chen","year":"2008","journal-title":"Hypertension."},{"key":"2024020317581080900_bib4","doi-asserted-by":"crossref","first-page":"16810","DOI":"10.1073\/pnas.0611202104","article-title":"Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals","volume":"104","author":"Bodyak","year":"2007","journal-title":"Proc Natl Acad Sci USA."},{"key":"2024020317581080900_bib5","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/j.jacc.2008.08.050","article-title":"Vitamin D deficiency an important, common, and easily treatable cardiovascular risk factor?","volume":"52","author":"Lee","year":"2008","journal-title":"J Am Coll Cardiol."},{"key":"2024020317581080900_bib6","doi-asserted-by":"crossref","first-page":"E125","DOI":"10.1152\/ajpendo.00224.2004","article-title":"Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems","volume":"288","author":"Xiang","year":"2005","journal-title":"Am J Physiol Endocrinol Metab."},{"key":"2024020317581080900_bib7","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/ki.2008.101","article-title":"Calcium-independent and 1,25(OH)2D3-dependent regulation of the renin-angiotensin system in 1alpha-hydroxylase knockout mice","volume":"74","author":"Zhou","year":"2008","journal-title":"Kidney Int."},{"key":"2024020317581080900_bib8","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1210\/en.2007-0805","article-title":"Functional vitamin D receptor (VDR) in the t-tubules of cardiac myocytes: VDR knockout cardiomyocyte contractility","volume":"149","author":"Tishkoff","year":"2008","journal-title":"Endocrinology."},{"key":"2024020317581080900_bib9","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.jsbmb.2006.12.098","article-title":"Characterization of heart size and blood pressure in the vitamin D receptor knockout mouse","volume":"103","author":"Simpson","year":"2007","journal-title":"J Steroid Biochem Mol Biol."},{"key":"2024020317581080900_bib10","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.ecl.2010.02.004","article-title":"Genetic disorders and defects in vitamin d action","volume":"39","author":"Malloy","year":"2010","journal-title":"Endocrinol Metab Clin North Am."},{"key":"2024020317581080900_bib11","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1210\/er.2008-0004","article-title":"Vitamin D and human health: lessons from vitamin D receptor null mice","volume":"29","author":"Bouillon","year":"2008","journal-title":"Endocr Rev."},{"key":"2024020317581080900_bib12","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1210\/jcem.86.5.7448","article-title":"The role of the vitamin D receptor in regulating vitamin D metabolism: a study of vitamin D-dependent rickets, type II","volume":"86","author":"Tiosano","year":"2001","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020317581080900_bib13","first-page":"2836","article-title":"Selective modulation by vitamin D of renal response to parathyroid hormone: a study in calcitriol-resistant rickets","volume":"81","author":"Even","year":"1996","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020317581080900_bib14","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1172\/JCI114944","article-title":"The molecular basis of hereditary 1,25-dihydroxyvitamin D3 resistant rickets in seven related families","volume":"86","author":"Malloy","year":"1990","journal-title":"J Clin Invest."},{"key":"2024020317581080900_bib15","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1210\/jcem-55-5-1020","article-title":"Vitamin D resistant rickets with alopecia: cultured skin fibroblasts exhibit defective cytoplasmic receptors and unresponsiveness to 1,25(OH)2D3","volume":"55","author":"Feldman","year":"1982","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020317581080900_bib16","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1126\/science.2849209","article-title":"Point mutations in the human vitamin D receptor gene associated with hypocalcemic rickets","volume":"242","author":"Hughes","year":"1988","journal-title":"Science."},{"key":"2024020317581080900_bib17","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S0022-3476(05)81919-5","article-title":"Calcium therapy for calcitriol-resistant rickets","volume":"121","author":"Hochberg","year":"1992","journal-title":"J Pediatr."},{"key":"2024020317581080900_bib18","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/0002-9343(87)90666-8","article-title":"Long-term intracaval calcium infusion therapy in end-organ resistance to 1,25-dihydroxyvitamin D","volume":"83","author":"Weisman","year":"1987","journal-title":"Am J Med."},{"key":"2024020317581080900_bib19","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S0735-1097(88)80060-3","article-title":"Echocardiographically determined left ventricular mass index in normal children, adolescents and young adults","volume":"12","author":"Daniels","year":"1988","journal-title":"J Am Coll Cardiol."},{"key":"2024020317581080900_bib20","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1471-2342-9-2","article-title":"Age and gender specific normal values of left ventricular mass, volume and function for gradient echo magnetic resonance imaging: a cross sectional study","volume":"9","author":"Cain","year":"2009","journal-title":"BMC Med Imaging."},{"key":"2024020317581080900_bib21","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/j.1475-097X.2007.00735.x","article-title":"Physiological determinants of the variation in left ventricular mass from early adolescence to late adulthood in healthy subjects","volume":"27","author":"Cain","year":"2007","journal-title":"Clin Physiol Funct Imaging."},{"key":"2024020317581080900_bib22","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1016\/0735-1097(92)90617-V","article-title":"Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension","volume":"19","author":"Ganau","year":"1992","journal-title":"J Am Coll Cardiol."},{"key":"2024020317581080900_bib23","first-page":"59","article-title":"Determination of left ventricular mass by echocardiography in normal Arab people","volume":"14","author":"Mohammad","year":"2001","journal-title":"Med J Islamic. Acad Sci."},{"key":"2024020317581080900_bib24","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1542\/peds.114.S2.555","article-title":"National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents","volume":"114","year":"2004","journal-title":"Pediatrics."},{"key":"2024020317581080900_bib25","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1136\/heart.83.6.667","article-title":"Normal values of M mode echocardiographic measurements of more than 2000 healthy infants and children in central Europe","volume":"83","author":"Kampmann","year":"2000","journal-title":"Heart."},{"key":"2024020317581080900_bib26","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1161\/CIRCULATIONAHA.107.741157","article-title":"A novel method of expressing left ventricular mass relative to body size in children","volume":"117","author":"Foster","year":"2008","journal-title":"Circulation."},{"key":"2024020317581080900_bib27","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/sj.jhh.1001546","article-title":"Reduced nocturnal fall in blood pressure, assessed by two ambulatory blood pressure monitorings and cardiac alterations in early phases of untreated essential hypertension","volume":"17","author":"Cuspidi","year":"2003","journal-title":"J Hum Hypertens."},{"key":"2024020317581080900_bib28","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1016\/j.echo.2005.10.005","article-title":"Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology","volume":"18","author":"Lang","year":"2005","journal-title":"J Am Soc Echocardiogr."},{"key":"2024020317581080900_bib29","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1161\/CIRCIMAGING.108.768911","article-title":"Aortic root measurement by cardiovascular magnetic resonance: specification of planes and lines of measurement and corresponding normal values","volume":"1","author":"Burman","year":"2008","journal-title":"Circ Cardiovasc Imaging."},{"key":"2024020317581080900_bib30","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1172\/JCI0215219","article-title":"1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system","volume":"110","author":"Li","year":"2002","journal-title":"J Clin Invest."},{"key":"2024020317581080900_bib31","doi-asserted-by":"crossref","first-page":"307","DOI":"10.7326\/0003-4819-152-5-201003020-00009","article-title":"Systematic review: Vitamin D and cardiometabolic outcomes","volume":"152","author":"Pittas","year":"2010","journal-title":"Ann Intern Med."},{"key":"2024020317581080900_bib32","doi-asserted-by":"crossref","first-page":"315","DOI":"10.7326\/0003-4819-152-5-201003020-00010","article-title":"Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events","volume":"152","author":"Wang","year":"2010","journal-title":"Ann Intern Med."},{"key":"2024020317581080900_bib33","first-page":"156","article-title":"The vitamin D receptor and the syndrome of hereditary 1,25-dihydroxyvitamin D-resistant rickets","volume":"20","author":"Malloy","year":"1999","journal-title":"Endocr Rev."},{"key":"2024020317581080900_bib34","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1161\/HYPERTENSIONAHA.108.190329","article-title":"Ambulatory blood pressure monitoring in children and adolescents: recommendations for standard assessment: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee of the council on cardiovascular disease in the young and the council for high blood pressure research","volume":"52","author":"Urbina","year":"2008","journal-title":"Hypertension."},{"key":"2024020317581080900_bib35","article-title":"Membrane localization, Caveolin-3 association and rapid actions of vitamin D receptor in cardiac myocytes","author":"Zhao","year":"2009","journal-title":"Steroids."},{"key":"2024020317581080900_bib36","doi-asserted-by":"crossref","first-page":"29821","DOI":"10.1074\/jbc.M705495200","article-title":"1,25-dihydroxyvitamin D3 suppresses renin gene transcription by blocking the activity of the cyclic AMP response element in the renin gene promoter","volume":"282","author":"Yuan","year":"2007","journal-title":"J Biol Chem."},{"key":"2024020317581080900_bib37","doi-asserted-by":"crossref","first-page":"8153","DOI":"10.1073\/pnas.95.14.8153","article-title":"Localization of tumor suppressor activity important in nonsmall cell lung carcinoma on chromosome 11q","volume":"95","author":"Murakami","year":"1998","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2024020317581080900_bib38","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1161\/01.RES.0000071355.82009.43","article-title":"Identification of a nuclear orphan receptor (Ear2) as a negative regulator of renin gene transcription","volume":"92","author":"Liu","year":"2003","journal-title":"Circ Res."},{"key":"2024020317581080900_bib39","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1161\/01.HYP.38.3.332","article-title":"NF-Y antagonizes renin enhancer function by blocking stimulatory transcription factors","volume":"38","author":"Shi","year":"2001","journal-title":"Hypertension."},{"key":"2024020317581080900_bib40","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1161\/HYPERTENSIONAHA.109.148619","article-title":"Plasma 25-hydroxyvitamin D and regulation of the renin-angiotensin system in humans","volume":"55","author":"Forman","journal-title":"Hypertension."},{"key":"2024020317581080900_bib41","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1210\/jc.2010-2704","article-title":"The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know","volume":"96","author":"Ross","year":"2011","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020317581080900_bib42","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/0002-9343(84)90516-3","article-title":"1,25-Dihydroxyvitamin D resistance, rickets, and alopecia","volume":"77","author":"Hochberg","year":"1984","journal-title":"Am J Med."},{"key":"2024020317581080900_bib43","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1210\/jcem-60-3-490","article-title":"Vitamin D resistance and alopecia: a kindred with normal 1,25-dihydroxyvitamin D binding, but decreased receptor affinity for deoxyribonucleic acid","volume":"60","author":"Hirst","year":"1985","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020317581080900_bib44","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1210\/jcem-59-3-383","article-title":"1,25-dihydroxyvitamin D resistance, rickets, and alopecia: analysis of receptors and bioresponse in cultured fibroblasts from patients and parents","volume":"59","author":"Chen","year":"1984","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020317581080900_bib45","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1515\/JPEM.2007.20.3.425","article-title":"Hereditary vitamin D-resistant rickets in Greek children: genotype, phenotype, and long-term response to treatment","volume":"20","author":"Nicolaidou","year":"2007","journal-title":"J Pediatr Endocrinol Metab."},{"key":"2024020317581080900_bib46","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/S0026-0495(97)90078-0","article-title":"Estrogen therapy enhances calcium absorption and retention and diminishes bone turnover in young girls with Turner's syndrome: a calcium kinetic study","volume":"46","author":"Mauras","year":"1997","journal-title":"Metabolism."},{"key":"2024020317581080900_bib47","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1359\/jbmr.1999.14.1.57","article-title":"Evidence for involvement of 17beta-estradiol in intestinal calcium absorption independent of 1,25-dihydroxyvitamin D3 level in the Rat","volume":"14","author":"Colin","year":"1999","journal-title":"J Bone Miner Res."},{"key":"2024020317581080900_bib48","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1359\/jbmr.2003.18.10.1725","article-title":"Intestinal calcium transporter genes are upregulated by estrogens and the reproductive cycle through vitamin D receptor-independent mechanisms","volume":"18","author":"Van Cromphaut","year":"2003","journal-title":"J Bone Miner Res."},{"key":"2024020317581080900_bib49","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1210\/en.2009-1010","article-title":"Pregnancy up-regulates intestinal calcium absorption and skeletal mineralization independently of the vitamin D receptor","volume":"151","author":"Fudge","year":"2010","journal-title":"Endocrinology."},{"key":"2024020317581080900_bib50","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1172\/JCI112714","article-title":"Regulation by vitamin D metabolites of parathyroid hormone gene transcription in vivo in the rat","volume":"78","author":"Silver","year":"1986","journal-title":"J Clin Invest."},{"key":"2024020317581080900_bib51","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1055\/s-2007-1012353","article-title":"Effect of parathyroid hormone on plasma renin activity in humans","volume":"18","author":"Broulik","year":"1986","journal-title":"Horm Metab Res."}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.431","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/26\/9\/2252\/56557918\/431_ftp.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/26\/9\/2252\/56557918\/431_ftp.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T15:07:09Z","timestamp":1710342429000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/26\/9\/2252-2260\/7597947"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5,16]]},"references-count":51,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2011,5,16]]},"published-print":{"date-parts":[[2011,9,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.431","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,9,1]]},"published":{"date-parts":[[2011,5,16]]}}}