|
|
||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Departments of 1Medicine and 3Pathology and 4Functional Genomics Facility, University of Chicago, Chicago, Illinois; and 2Diabetes Center and Department of Medicine, University of California, San Francisco, California
Submitted 27 May 2004 ; accepted in final form 12 September 2004
Our recent studies suggest that 1,25-dihydroxyvitamin D3 functions as an endocrine suppressor of renin biosynthesis. Genetic disruption of the vitamin D receptor (VDR) results in overstimulation of the renin-angiotensin system (RAS), leading to high blood pressure and cardiac hypertrophy. Consistent with the higher heart-to-body weight ratio, the size of left ventricular cardiomyocytes in VDR knockout (KO) mice was markedly increased compared with wild-type (WT) mice. As expected, levels of atrial natriuretic peptide (ANP) mRNA and circulating ANP were also increased in VDRKO mice. Treatment of VDRKO mice with captopril reduced cardiac hypertrophy and normalized ANP expression. To investigate the role of the cardiac RAS in the development of cardiac hypertrophy, the expression of renin, angiotensinogen, and AT-1a receptor in the heart was examined by real-time RT-PCR and immunostaining. In VDRKO mice, the cardiac renin mRNA level was significantly increased, and this increase was further amplified by captopril treatment. Consistently, intense immunostaining was detected in the left ventricle of captopril-treated WT and VDRKO mice by use of an anti-renin antibody. Levels of cardiac angiotensinogen and AT-1a receptor mRNAs were unchanged in the mutant mice. These data suggest that the cardiac hypertrophy seen in VDRKO mice is a consequence of activation of both the systemic and cardiac RAS and support the notion that 1,25-dihydroxyvitamin D3 regulates cardiac functions, at least in part, through the RAS.
atrial natriuretic peptide; cardiomyocyte; hypertension; captopril
This article has been cited by other articles:
![]() |
J. M. Valdivielso, J. Cannata-Andia, B. Coll, and E. Fernandez A new role for vitamin D receptor activation in chronic kidney disease Am J Physiol Renal Physiol, December 1, 2009; 297(6): F1502 - F1509. [Abstract] [Full Text] [PDF] |
||||
![]() |
C J Ferro, C D Chue, R P Steeds, and J N Townend Is lowering phosphate exposure the key to preventing arterial stiffening with age? Heart, November 1, 2009; 95(21): 1770 - 1772. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Thadhani Is Calcitriol Life-Protective for Patients with Chronic Kidney Disease? J. Am. Soc. Nephrol., November 1, 2009; 20(11): 2285 - 2290. [Full Text] [PDF] |
||||
![]() |
J. N. Artaza, R. Mehrotra, and K. C. Norris Vitamin D and the Cardiovascular System Clin. J. Am. Soc. Nephrol., September 1, 2009; 4(9): 1515 - 1522. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Zhang, D. K. Deb, J. Kong, G. Ning, Y. Wang, G. Li, Y. Chen, Z. Zhang, S. Strugnell, Y. Sabbagh, et al. Long-term therapeutic effect of vitamin D analog doxercalciferol on diabetic nephropathy: strong synergism with AT1 receptor antagonist Am J Physiol Renal Physiol, September 1, 2009; 297(3): F791 - F801. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. P. Reis, D. von Muhlen, E. R. Miller III, E. D. Michos, and L. J. Appel Vitamin D Status and Cardiometabolic Risk Factors in the United States Adolescent Population Pediatrics, September 1, 2009; 124(3): e371 - e379. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. L. Melamed and R. Thadhani Low Calcidiol Levels and Coronary Artery Calcification: True, True, and Related? J. Am. Soc. Nephrol., August 1, 2009; 20(8): 1663 - 1665. [Full Text] [PDF] |
||||
![]() |
D. V. Barreto, F. C. Barreto, S. Liabeuf, M. Temmar, F. Boitte, G. Choukroun, A. Fournier, and Z. A. Massy Vitamin D Affects Survival Independently of Vascular Calcification in Chronic Kidney Disease Clin. J. Am. Soc. Nephrol., June 1, 2009; 4(6): 1128 - 1135. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. M. Gutierrez, J. L. Januzzi, T. Isakova, K. Laliberte, K. Smith, G. Collerone, A. Sarwar, U. Hoffmann, E. Coglianese, R. Christenson, et al. Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Chronic Kidney Disease Circulation, May 19, 2009; 119(19): 2545 - 2552. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Covic, P. Kothawala, M. Bernal, S. Robbins, A. Chalian, and D. Goldsmith Systematic review of the evidence underlying the association between mineral metabolism disturbances and risk of all-cause mortality, cardiovascular mortality and cardiovascular events in chronic kidney disease Nephrol. Dial. Transplant., May 1, 2009; 24(5): 1506 - 1523. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Koleganova, G. Piecha, E. Ritz, and M.-L. Gross Calcitriol ameliorates capillary deficit and fibrosis of the heart in subtotally nephrectomized rats Nephrol. Dial. Transplant., March 1, 2009; 24(3): 778 - 787. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Y.-M. Wang, J. E Sanderson, M. Wang, S.-F. Lui, M. M.-M. Sea, J. Woo, C. W.-K. Lam, and I. H.-S. Chan Reply to C Fourtounas and JG Vlachojannis Am. J. Clinical Nutrition, January 1, 2009; 89(1): 436 - 438. [Full Text] [PDF] |
||||
![]() |
S. Chen, D. J. Glenn, W. Ni, C. L. Grigsby, K. Olsen, M. Nishimoto, C. S. Law, and D. G. Gardner Expression of the Vitamin D Receptor Is Increased in the Hypertrophic Heart Hypertension, December 1, 2008; 52(6): 1106 - 1112. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. E. Wallis, S. Penckofer, and G. W. Sizemore The "Sunshine Deficit" and Cardiovascular Disease Circulation, September 30, 2008; 118(14): 1476 - 1485. [Full Text] [PDF] |
||||
![]() |
W. Al-Badr and K. J. Martin Vitamin D and Kidney Disease Clin. J. Am. Soc. Nephrol., September 1, 2008; 3(5): 1555 - 1560. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. L. Melamed, E. D. Michos, W. Post, and B. Astor 25-Hydroxyvitamin D Levels and the Risk of Mortality in the General Population Arch Intern Med, August 11, 2008; 168(15): 1629 - 1637. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Giovannucci, Y. Liu, B. W. Hollis, and E. B. Rimm 25-Hydroxyvitamin D and Risk of Myocardial Infarction in Men: A Prospective Study Arch Intern Med, June 9, 2008; 168(11): 1174 - 1180. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Y.-M. Wang, C. W.-K. Lam, J. E Sanderson, M. Wang, I. H.-S. Chan, S.-F. Lui, M. M.-M. Sea, and J. Woo Serum 25-hydroxyvitamin D status and cardiovascular outcomes in chronic peritoneal dialysis patients: a 3-y prospective cohort study, Am. J. Clinical Nutrition, June 1, 2008; 87(6): 1631 - 1638. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. B. Pai and T. A. Conner Oxidative Stress and Inflammation in Chronic Kidney Disease: Role of Intravenous Iron and Vitamin D Journal of Pharmacy Practice, June 1, 2008; 21(3): 214 - 224. [Abstract] [PDF] |
||||
![]() |
M. L. Melamed, P. Muntner, E. D. Michos, J. Uribarri, C. Weber, J. Sharma, and P. Raggi Serum 25-Hydroxyvitamin D Levels and the Prevalence of Peripheral Arterial Disease: Results from NHANES 2001 to 2004 Arterioscler Thromb Vasc Biol, June 1, 2008; 28(6): 1179 - 1185. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Talmor, E. Golan, S. Benchetrit, J. Bernheim, O. Klein, J. Green, and G. Rashid Calcitriol blunts the deleterious impact of advanced glycation end products on endothelial cells Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1059 - F1064. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Zittermann, S. S. Schleithoff, C. Gotting, O. Dronow, U. Fuchs, J. Kuhn, K. Kleesiek, G. Tenderich, and R. Koerfer Poor outcome in end-stage heart failure patients with low circulating calcitriol levels Eur J Heart Fail, March 1, 2008; 10(3): 321 - 327. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. J. Wang, M. J. Pencina, S. L. Booth, P. F. Jacques, E. Ingelsson, K. Lanier, E. J. Benjamin, R. B. D'Agostino, M. Wolf, and R. S. Vasan Vitamin D Deficiency and Risk of Cardiovascular Disease Circulation, January 29, 2008; 117(4): 503 - 511. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Yuan, W. Pan, J. Kong, W. Zheng, F. L. Szeto, K. E. Wong, R. Cohen, A. Klopot, Z. Zhang, and Y. C. Li 1,25-Dihydroxyvitamin D3 Suppresses Renin Gene Transcription by Blocking the Activity of the Cyclic AMP Response Element in the Renin Gene Promoter J. Biol. Chem., October 12, 2007; 282(41): 29821 - 29830. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Tian, Y. Liu, L. A. Williams, and D. de Zeeuw Potential role of active vitamin D in retarding the progression of chronic kidney disease Nephrol. Dial. Transplant., February 1, 2007; 22(2): 321 - 328. [Full Text] [PDF] |
||||
![]() |
P.T. Liu, S. Stenger, H. Li, L. Wenzel, B.H. Tan, S.R. Krutzik, M.T. Ochoa, J. Schauber, K. Wu, C. Meinken, et al. Vitamin D3-Triggered Antimicrobial Response--Another Pleiotropic Effect beyond Mineral and Bone Metabolism: Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response. Science 311: 1770-1773, 2006 J. Am. Soc. Nephrol., November 1, 2006; 17(11): 2949 - 2953. [Full Text] [PDF] |
||||
![]() |
M. Tonelli, F. Sacks, M. Pfeffer, Z.H. Gao, G. Curhan, for the Cholesterol and Recurrent Events (CARE) Tr, P. Rossing, K. Rossing, P. Gaede, O. Pedersen, et al. Serum Phosphate: A Novel Cardiovascular Risk Factor Even in Nonrenal Patients: Relation between Serum Phosphate Level and Cardiovascular Event Rate in People with Coronary Disease. Circulation 112: 2627-2633, 2005 J. Am. Soc. Nephrol., August 1, 2006; 17(8): 2077 - 2085. [Full Text] [PDF] |
||||
![]() |
S. S Schleithoff, A. Zittermann, G. Tenderich, H. K Berthold, P. Stehle, and R. Koerfer Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am. J. Clinical Nutrition, April 1, 2006; 83(4): 754 - 759. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |