Vitamin D and Cardiovascular Disease
Khanh Vinh Quoc Luong* and Lan Thi Hoang Nguyen
Vietnamese American Medical Research Foundation, Westminster, California,
14971 Brookhurst Street, Westminster, CA. 92683, USA
*Address correspondence to this author at the Vietnamese American Medical Research Foundation, Westminster, California, 14971 Brookhurst Street, Westminster, CA. 92683, USA; Tel: (714) 839-5898; Fax: (714) 839-5989; E-mail: Lng2687765@aol.com

Current Medicinal Chemistry, 2006, Volume 13, Number 20, Pages 2443-2447
Abstract: Cardiovascular disease (CVD) is the leading cause of death among patients with end-stage renal disease (ESRD). Vitamin D deficiency accompanies the loss of kidney function and is extremely common. Treatment with active vitamin D has improved survival rate in dialysis patients. The relationship between vitamin D and CVD has been reported in the literature. Genetic factors have been known to cause both vitamin D deficiency and CVD. Vitamin D receptor is found in the heart muscle. Vitamin D is reported to be involved in the pathogenesis of many cardiovascular problems. Certainly, vitamin D has an important role in modulating CVD.
Keywords: Vitamin D, cardiovascular disease.
INTRODUCTION
The relationship between vitamin D and cardiovascular risk factors has been discussed in the literature. In a survey of cardiovascular risk factors, Auwerx et al. [1] found an independent and highly significant positive correlation between serum concentrations of 25-hydroxyvitamin D3 (25OHD3) and lipid profiles, such as apolipoprotein A-1 (Apo A-1) and high density lipoprotein (HDL) cholesterol. These lipid profiles have been known to be associated with cardiovascular risk. In another studies [2], long-term vitamin
D3 supplementation may have adverse effects on serum lipids during post-menopausal hormone replacement therapy. However, Lips et al. [3] found no effect of vitamin D supplementation in serum total and HDL-cholesterol levels in elderly institutionalized patients with low serum vitamin D concentrations. The blood pressure (BP) is another contributing factor in cardiovascular disease (CVD); Argiles et al. [4] reported a correlation between BP and vitamin D levels in dialysis patients. Acute administration of 1,25-
dihydroxyvitamin D3 (1,25OHD3) caused a fast decrease in cardiac output and a transient BP increase in hypertensive patients [5]. Therefore, it would be interesting to further review the role of vitamin D in CVD.
RISK FACTORS
For Both Vitamin D Deficiency and Cardiovascular Diseases
Genetic studies provide excellent opportunities to link molecular variations with epidemiological data. DNA sequences variations, as polymorphisms, have modest and subtle but true biological effects. Certain allelic variations in the vitamin D receptor (VDR) may also be of genetic risk for CVD (Table 1). Ortlepp et al [6] found a significant association of VDR polymorphism with calcified aortic valve stenosis, especially the B allele of the VDR. Interestingly, the B allele has been associated with low bone mineral density, impaired calcium absorption, more rapid bone loss, and increased PTH concentrations [7]. To test
whether the osteoporosis and cardiovascular disease may share common risk factor, Kammerer et al. [8] evaluated allelic variation of VDR influenced joint variation in low bone mineral density (BMD) and intimal medial thickening (IMT) of the common carotid artery, a marker of sub-clinical atherosclerosis in women. They noticed that the VDR BsmI BB genotype was associated with significantly higher forearm BMD, higher IMT, and higher spine BMD in older women. The association of the VDR genotype with IMT was independent of its association with BMD. They concluded that VDR polymorphisms may be one of multiple factors influencing the joint risk of atherosclerosis and osteoporosis. Shiraki et al. [9] found an association of BMD with Apo E phenotype; this phenotype was related to the cardiovascular risk in diabetes mellitus [10]. Lee et al. [11] reported the first data that suggest the common genetic polymorphism in the VDR associated with BP and hypertension risk. The genotype of the VDR polymorphism has also been known to determine the prevalence of type 2 diabetes mellitus and CAD in a high-risk cohort population [12]. There is epidemiological evidence that the risk for CAD is inversely associated with plasma calcitriol level [13]. Moreover, a frequent BsmI polymorphism of the VDR was reported to be highly correlated with serum calcitriol levels [14-15]. Van Schooten et al. [16] also found that individuals with severe CAD were more likely to contain the VDR genotype bb. The bb genotype has been shown to be associated with low levels of circulating calcitriol [14]. CVD is the leading cause of death among patients with end-stage renal disease (ESRD). However, Marco et al. [17] found that VDR gene BsmI polymorphism may influences survival rate in hemodialysis (HD) patients. These influences may independently affect both hemoglobin/hematocrit levels and dose of erythropoietin in HD patients [18].
The cytochrome P450 (CYP) is responsible for the oxidation, peroxidation, and/or reduction of vitamins, steroids, xenobiotics, and metabolism of drugs. There were associations between allelic variants of cytochrome P450, CYP2C8 and CYP2C9, and modest increase risk of acute myocardial infarction (AMI) in female [19]. In another studies [20], CYP2C9*3 frequency of hypertensive Chinese female patients was significantly lower than that of healthy controls. Yu et al. [20] suggested that CYP2C9*3 had a secondary protective effect in females. However, expression of CYP2C9 is regulated by the VDR [21].
Tissue matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) have been known to control remodeling in vascular wall and myocardium as well as in other tissues. There were strong positive independent contributions of increases in both BP and circulating MMP9 to increases in TIMP-1 levels. However, the VDR Taql polymorphism was a major independent determinant of circulating TIMP-1 [22]. Picard et al. [23] revealed the increased cardiac mRNA expression of MMP-1 and TIMP-1 in dilated cardiomyopathy. Plasma MMP9 and MMP2 levels have been increased in the circulation in unstable angina and acute infarction [24-26]. High MMP-9/TIMP-1 ratio was also reported to be associated with stroke patients (total anterior circulation infarction) [27]. Interestingly, calcitriol modulates tissue MMP expression experimentally [28].
Recently, Xiang et al. [29] reported cardiac hypertrophy and hypertension in VDR knockout mice. Their other studies [30] also suggested that 1,25OHD3 functions as an endocrine suppressor of renin biosynthesis. Geneticdisruption of the VDR results in overstimulation of the renin-angiotensin system (RAS), leading to high BP and cardiac hypertrophy. Treatment with captopril reduced cardiac hypertrophy in VDR knockout mice [29].
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Table 1. Relationship Between Allelic Variations in Vitamin D Receptor (VDR) and Cardiovascular Disease (CVD)
Linked to
DIRECT
VDR Polymorphism Calcified Aortic Valve Stenosis
IMT
Hypertension
INDIRECT via
Calcitriol (1,25OHD3) Coronary Artery Disease
CYP2C9 Acute Myocardial Infarction
TIMP-1 levels Control remodeling in Vascular & Myocardial
Hypertension
MMP9
MMP9 & MMP2 Unstable Angina & Acute Myocardial Infarction (1,25OHD3 modulates MMP expression)
MMP1 Dilated Cardiomyopathy
MMP-9/TIMP-1 Strokes
RAS Hypertension & Cardiac Hypertrophy
* IMT (intimal medial thickening of the common carotid artery); CYP (Cytochrome P450); TIMP (Tissue Inhibitor of Metalloproteinase); MMP (Matrix Metalloproteinase);
RAS (The Renin-Angiotensin System).
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ROLE OF VITAMIN D IN CARDIOVASCULAR DISEASES:
Obesity has been known as an important risk factor in causing heart disease and stroke. Calcitriol was reported to inhibit the adipogenesis in the murine 3T3-L1 cell line [31]. These cell lines have provided an ideal model system to understand adipocyte development. In mice, Calcitriol was also demonstrated to inhibit bone marrow adipogenesis [32]. Lee et al. [33] suggested that calcitriol-mediated induction of the endoplasmic reticulum (ER) protein Insig-2 in 3T3-L1 adipocytes might lead to the inhibition of adipogenesis by preventing the transcription factor, sterol regulatory elementbinding protein 1c (SREBP-1C), from reaching nucleus. Recently, Blumberg et al. [34] have further defined the molecular mechanism by which the unliganded VDR and calcitriol-liganded VDR regulate adipogenesis. In the presence of Calcitriol, the VDR blocks adipogenesis by down-regulating both CCAAT/enhancer-binding Protein b (C/EBPb) mRNA expression and C/EBPb nuclear protein levels at a critical stage of differentiation. In the absence of Calcitriol, the unliganded VDR appears necessary for lipid accumulation as knockdown of the VDR using siRNA both delays and prevent this process.
Serum lipid profiles have been known as a risk factor in contributing to the CVD. Administration of either 25OHD3 or 1-a-hydroxy-vitamin D3 lowered risk for cardiovascular mortality in HD patients [35-36]. 1,25OHD3 was also reported to correct lipid abnormalities in uremia [37].
Triglyceride and the ratio of triglyceride to HDL-cholesterol significantly decreased following vitamin D therapy [38]. Significant increases in HDL-cholesterol and Apo-A1 were noted during calcitriol treatment in HD patients [39]. In another study [40], low-density lipoprotein-cholesterol (LDL-C) plasma values were inversely correlated with both intake and plasma vitamin D levels. Hypovitaminosis D has also been known to associate with reductions in serum Apo A1 [41]. The lipoprotein-macrophage interactions have been known as a model for foam cell development and atherogenesis. 1,25OHD3-induced alterations of lipid metabolism in human monocyte-macrophages [42]. 1,25OHD3 also has been shown to inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) in cholesterol biosynthesis [43]. The effect of 1,25OHD3
effects on the lipid profile is summarized in Table 2.
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Table 2. Vitamin D Effects on the Lipid Profile
Triglyceride Decreased
Triglyceride/HDL-Cholesterol Decreased
LDL-Cholesterol Decreased
HDL-Cholesterol Increased
Lipoprotein A1 (Apo-A1) Increased
Macrophages Alteration of the Lipid Metabolism
HMG-CoA Reductase Inhibited
*LDL (Low Density Lipoprotein); HDL (High Density Lipoprotein); HMG-CoA (3-
hydroxy-3-methylglutaryl coenzyme A reductase)
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Vitamin D and Cardiovascular Disease Current Medicinal Chemistry, 2006 Vol. 13, No. 20 2445\
1,25OHD3 may affect on cardiovascular function either by direct or indirect action (by suppression of PTH levels). Myocardial diseases are commonly seen in ESRD, which is accompanied by a secondary elevation of PTH levels due to the hypocalcemia and the impaired production of 1,25OHD3. Studies of this phenomenon have provided evidence for inotropic [44] and chronotropic [45] effects of PTH on isolated cardiac papillary muscle and cultured myocardial cells, respectively. The latter phenomenon was calciumdependent and seemed to be related to the calcium entry into the cells [46]. In dog, both positive inotropic and chronotropic responses were observed and were dissociated from vasodilator effects of PTH on coronary arteries [46]. Additionally, Baczynski et al. [47] demonstrated that PTHenhanced calcium entry and its accumulation result in impaired myocardial energy metabolism in the rat. Piovesan et al. [48] also confirmed the high prevalence of left ventricular (LV) hypertrophy, measured by LV mass index (LVMI), in primary hyperparathyroidism. After surgical removal of parathyroid gland, LVMI decreased.
Fahrleitner et al. [49] founded that patients with severe peripheral artery disease (PAD) had a high prevalence of vitamin D deficiency and impaired bone turnover. Furthermore, Weishaar et al. [50] have shown that 1,25OHD3 deficiency is associated with aberrant cardiac contractility and hypertrophy in a rodent model. Morphometric analysis of cross-section of ventricular tissue taken from the hearts of vitamin D-deficient animals revealed an increase in collagen content, largely confined to the interstitial compartment [51], as well as changing in the myosin isozyme profile in vitamin D-deficient subjects [52].
Vitamin D deficiency also resulted in enhanced rate of decline of the intracellular high-energy phosphorus compounds [53].
In the cardiac myocyte, vitamin D enhances calcium transport across the plasma membrane by a mechanism resembling a receptor-mediated phenomenon [54]. 1,25OHD3 through its receptor, VDR, has important physiological effects, such as: calcium transport, cell growth and differentiation. High-affinity receptors for 1,25OHD3 have been identified in both myocardial [55] and vascular smooth muscle [56] cells, where 1,25OHD3 plays a role in regulating proto-oncogene expression, cell growth, and mitogenesis [57-58]. VDRs are also present in vascular endothelial cells [59-60]; these cells may possess 1- hydroxylase activity that is the capable to synthesize 1,25OHD3. Increased circulating concentrations 1,25OHD3 reduce the risk of coronary calcification of atherosclerotic vessels [61], and low 1,25OHD3 in ESRD is associated with vascular calcification [62]. These findings also suggest a role of 1,25OHD3 in the development of vascular calcification. Ectopic calcification is a common problem associated with CVD. Several studies have suggested vascular smooth muscle cells as one of the primary cell types associated with arterial calcification. In vitamin D deficiency, vascular smooth muscle cells may be transformed during coronary calcification in to cells resembling osteoblasts [63]. Giachelli demonstrated that smooth muscle cell culture mineralization is associated osteoblast-like properties, including expression of osteoblast differentiation factor, core-binding factor-1 (Cbfa-1) [64]. Interestingly, active vitamin D has been known to suppress Cbfa-1 [65]. Therefore, vitamin D treatment may offset Cbfa-1 mediated coronary calcification and reduce CV mortality.
Fraga et al. [66] evaluated the ontogenesis of the VDR in fetal (17, 18, and 20 gestational days), neonatal (4 and 8 days), and adult rat heart, they showed the VDR protein localization in the nuclei of cardiac muscle fibers. They also founded that the VDR mRNA expression is changing over these different periods of development, significant differences in 20 days versus 18 days of fetal age. These changes in VDR expression may be related to other parameters associated with the development of the cardiac muscle and/or intracellular cardiac cell calcium homeostasis.
Adult cardiac myocytes lack mitotic capacity, they respond to growth stimuli largely through hypertrophy of existing myocardial cells rather than through an increase in cell number. Wu et al. [67] demonstrated that 1,25OHD3 and retinoic acid may antagonize endothelin-stimulated hypertrophy in a cultured neonatal rat cardiac ventriculocyte model. They have also shown that 1,25OHD3 negatively regulates expression of the endogenous atrial natriuretic peptide (ANP) gene [68] as well as a transfected human (h) ANP-chloramphenicol acetyltransferase (CAT) reporter in cultured rat atriocytes [69]. This inhibition was dose dependent with regard to both ligand and receptor. Reactivation of ANP secretion and ANP gene expression are considered as one of the earliest and most reliable markers of hypertrophy in the cardiac ventriculocyte [70]. O'Connell et al. [70] found that 1,25OHD3 directly regulate myocyte proliferation and induce myocyte hypertrophy 1,25OHD3 stimulated vascular endothelial growth factor release in aortic smooth muscle cells via p38 mitogen-activated protein kinase [71].
However, 1,25OHD3 inhibits angiogenesis, the formation of new blood vessels from an existing vascular bed, in vitro and in vivo [72].
Furthermore, vitamin D analogs, paricalcitol, downregulated the expression of natriuretic peptide and it was also reported to modulate on gene expression in human coronary artery smooth muscle cells [73]. Another natural metabolite of calcitriol, 1, 25-dihydroxy-3-epi-vitamin D3, was demonstrated to inhibit endothelial cells proliferated by causing Go/G1 arrest and induced apoptosis more effectively than 1,25OHD3 [74].
Interestingly, Thomasset et al. [75] have also shown that myocardial tissue contains a vitamin D-dependent calcium binding protein that is immunochemically similar to that found in intestine. The loss of such protein in cardiac muscle in vitamin D depletion might allow more cytosolic free calcium level increased after each depolarization, resulting in a greater muscle contraction.
There was also an evidence of non-genomic action of 1,25OHD3 in cardiac muscle; 1,25OHD3 involved in the activation of the 3',5'-cyclic AMP pathway [76], protein kinase A [77], protein kinase C [78], beta-adrenergicsensitive signal transduction pathway [79], and calcium channels [80] that regulated calcium influx. In addition, Shan et al. [81] also found the inhibition of membrane Ltype calcium channel activity and intracellular calcium concentration by 24,25-OHD3 in vascular smooth muscle. Selles et al. [82] found an involvement of the adenylate cyclase pathway and the participation of G proteins in 1,25OHD3 stimulation of calcium influx in chick heart cells. The demonstration of 1,25OHD3 modulation of calcium uptake in cardiac cells is a key step in establishing another non-genomic role for the hormone in cardiac muscle cell function.
SUMMARY
The relationship of vitamin D and CVD has been discussed. Many factors have been known to cause both vitamin D deficiency and CVD. Certainly, vitamin D has an important role in modulating CVD. It would be necessary to check vitamin D status in CVD. However, hypervitaminosis D may cause a serious problem. Hypervitaminosis D was demonstrated in animals with multiple cardionecrosis [83] and ultrastructural damage of cardiovascular lesions [84]. Paricalcitol, a vitamin D analog, treatment has been shown fewer episodes of hypercalcemia than calcitriol [85]. Whether vitamin D analogs have better situation than calcitriol in CVD is still under consideration.
REFERENCES
[1] Auwerx, J.; Bouillon, R.; Kesteloot, H. Arterioscler. Thromb., 1992, 12, 671.
[2] Heikkinen, A.M.; Tuppurainen, M.T.; Niskanen, L.; Komulainen, M.; Penttila, I.; Saarikoski, S. Eur. J. Endocrinol., 1997, 137, 495.
[3] Lips, P.; Wiersinga, A.; VanGinkel, F.C.; Jongen, M.J.M.; Netelenbos, J.C.; Hackeng, W.H.; Delmas, P.D.; van der Vijgh,
W.J. J. Clin. Endocrinol. Metab., 1988, 67, 644.
[4] Argiles, A.; Lorho, R., Servel, M.F., Couret, I., Chong, G.; 22. Mourad, G. Blood Purif., 2002, 20, 370. [40] Hooper, P.L.; Hooper, E.M.; Hunt, W.C.; Garry, P.J.; Goodwin,
[5] Jespersen, B.; Randlov, A.; Abrahamsen, J.; Fogh-Andersen, N.; J.S. Int. J. Vitam. Nutr. Res., 1983, 53, 412.
Olsen, N.V.; Kanstrup, I.L. Am. J. Hypertens., 1998, 11, 659. [41] John, W.G.; Noonan, K.; Mannan, N.; Boucher, B.J. Am. J. Clin.
[6] Ortlepp, J.R.; Hoffmann, R.; Ohme, F.; Lauscher, J.; Bleckmann, Nutr., 2005, 82, 517.
[7] Ferrari, S.; Manen, D.; Bonjour, J.P.; Slosman, D.; Rizzoli, R. J. J. Physiol., 1989, 257, E290.
Clin. Endocrinol. Metab., 1999, 84, 2043. [43] Gupta, A.K.; Sexton, A.C.; Rudney, H. J. Lipid Res., 1989, 30,
[8] Kammerer, C.M.; Dualan, A.A.; Samollow, P.B.; Perisse, A.R.; 379. Bauer, R.L.; MacCluer, J.W.; O'Leary, D.H.; Mitchell, B.D.
Calcif. Tissue Int., 2004, 75, 292.
[9] Shiraki, M.; Shiraki, Y.; Aoki, C.; Hosoi, T.; Inoue, S.; Kaneki, M.; Ouchi, Y. J. Bone Miner. Res., 1997, 12, 1438.
[10] Laakso, M.; Kesaniemi, A.; Kervinen, K.; Jauhiainen, M.; M.S. Am. J. Physiol., 1985, 249, E187.
[11] Lee, B.K., Lee, G.S.; Stewart, W.F.; Ahn, K.D.; Simon, D.; Brautbar N. Kidney. Int., 1985, 27, 718.
[12] Ortlepp, J.R.; Lauscher J.; Hoffmann, R.; Hanrath, P.; Joost, H.G. Diabet. Med., 2001, 18, 842.
[13] Scragg, R.; Jackson, R.; Holdaway, I.M.; Lim, T.; Beaglehole, R. Int. J. Epidemiol., 1990, 19, 559.
[14] Morrison, N.A.; Qi, J.C.; Tokita, A.; Kelly, P.J.; Crofts, L.; Nguyen, T.V.; Sambrook, P.N.; Eisman, J.A. Nature (London), 1994, 367, 284.
[15] Morrison, N.A.; Yeoman, R.; Kelly, P.J.; Eisman, J.A. Proc. Natl. Acad. Sci. USA, 1992, 89, 6665.
[16] Van Schooten, F.J.; Hirvonen, A.; Maas, L.M.; De Mol, B.A.; Kleinjans, J.C.; Bell, D.A.; Durrer, J.D. FASEB J., 1998, 12, 1409.
[17] Marco, M.P.; Craver, L.; Betriu, A.; Fibla, J.; Fernández, E. Am. J. Kidney Dis., 2001, 38, 965.
[18] Ertürk, S.; Kutlay, S.; Keven, K. J. Am. Soc. Nephrol., 2002, 39, 441.
[19] Yasar, U.; Bennett, A.M.; Eliasson, E.; Lundgren, S.; Wiman, B.; De Faire, U.; Rane, A. Pharmacogenetics, 2003, 13, 715.
[20] Yu, B.N.; Luo, C.H.; Wang, D.; Wang, A.; Li, Z.; Zhang, W.; Mo, W.; Zhou, H.H. Clin. Chim. Acta., 2004, 348, 57.
[21] Drocourt, L.; Ourlin, J.C.; Pascussi, J.M.; Maurel, P.;Vilarem, M.J. J. Biol. Chem., 2002, 277, 25125.
[22] Timms, P.M.; Mannan, N.; Hitman, G.A.; Noonan, K.; Mills, P.G.; Syndercombe-Court, D.; Aganna, E.; Price, C.P.; Boucher, B.J. Q.J. Med., 2002, 95, 787.
[23] Picard, F.; Brehm, M.; Fassbach, M.; Pelzer, P.; Scheuring, S.; Kury, P.; Strauer, B.E.; Schwartzkopff, P. Clin. Res. Cardiol., 2006, 95, 261.
[24] Koenig, W. Br. Med. J., 2000, 321, 187.
[25] Galis, Z.S.; Sukhova, G.K.; Lark, M.W.; Libby, P. J. Clin. Invest., 1994, 94, 2493.
[26] Kai, H.; Ikeda, H.; Yasukawa, H. J. Am. Coll. Cardiol., 1998, 32, 368.
[27] Vukasovic, I.; Tesija-Kuna, A.; Topic, E.; Supanc, V.; Demarin, V.; Petrovcic, M. Clin. Chem. Lab. Med., 2006, 44, 428.
[28] Dean, D.D.; Schwartz, Z.; Schmitz, J.; Muniz, O.E.; Lu, Y.; Calderon, F.; Howell, D.S.; Boyan, B.D. Connect. Tissue Res., 1996, 35, 331.
[29] Xiang, W.; Kong, J.; Chen, S.; Cao, L.P.; Qiao, G.; Zheng, W.; Liu, W.; Li, X.; Gardner, D.G.; Li, Y.C. Am. J. Phys. Endocrinol. Met., 2005, 288, E125.
[30] Li, Y.C.; Qiao, G.; Uskokovic, M.; Xiang, W.; Zheng, W.; Kong, J. J. Steroid Biochem. Mol. Biol., 2004, 89-90, 387.
[31] Kamei, Y.; Kawada, T.; Kazuki, R.; Ono, T.; Kato, S.; Sugimoto, E. Biochem. Biophys. Res. Comm., 1993, 193, 948.
[32] Kelly, K.A.; Gimble, J.M. Endocrinology, 1998, 139, 2622.
[33] Lee, S.; Lee, D.K; Choi, E.; Lee, J.W. Mol. Endocrinol., 2005, 19, 399.
[34] Blumberg, J.M; Tzameli, I.; Astapova, I.; Lam, F.S.; Flier, J.S.; Hollenberg, A.N. J. Biol. Chem., 2006, 281, 11205.
[35] Coratelli, P.; Petratrulo, F.; Buongiorno, M.; Giannattasio, M.; Buongiorno, E.; Passavanti, G.; Antonelli, G.; Capurso, A.;
Ferrannini, E.; Amerio, A. Contrib. Nephrol., 1984, 41, 433.
[36] Shoji, T.; Shinohara, K.; Kimoto, E.; Emoto, M.; Tahara, H.; Koyama, H.; Inaba, M.; Fukumoto, S.; Ishimura, E.; Miki, T.; Tabata, T.; Nishizawa, Y. Nephrol. Dial. Transpant., 2004, 19, 179.
[37] Mak, R.H. Kidney Int., 1998, 53, 1353.
[38] Khajehdehi, P. Scand J. Urol. Nephrol., 2000, 34, 62.
[39] Lim, P.S.; Hung, T.S.; Yeh, C.H.; Yu, M.H. Blood Purif., 1998, 16, Calcif. Tissue Int., 2004, 75, 292.
[40] Hooper, P.L.; Hoopr, E.M.; Hunt, W.C.; Gary, P.G.; Goodwin, J.S. Int. J. Vitam. Nutr. Res., 1983, 53, 412.
[41] John, P.L.; Noonan, K.; Mannan, N.; Boucher, B.J. Am. J. Clin. Nutr., 2005, 82, 517.
[42] Roullet, J.B.; Haluska, M.; Moichoisne, O.; McCarron, D.A. Am. J. Physiol., 1989, 257, È90.
[43] Guptq, A.K.; Sexton, A.C.; Rudney, H.J. Lipid Res., 1989, 30, 379.
[44] Katoh, Y.; Klein, K.L.; Kaplan, R.A.; Sanborn, W.G.; Kurokawa, K. Endocrinology, 1981, 109, 2252.
[45] Bogin, E.; Massry, S.G.; Harary, I. J. Clin. Invest., 1981, 67, 1215.
[46] Crass, M.F.; Moore, P.L.; Strickland, M.L.; Pang, P.K.T.; Citak, M.S. Am. J. Physiol., 1985, 249, É87.
[47] Baczynski, R.; Massry, S.G.; Kohan, R.; Magott, M.; Saglikes, Y.; Brautbar N. Kidney. Int., 1985, 27, 718.
[48] Piovesan, A.; Molineri, N.; Casasso, F.; Emmolo, I.; Ugliengo, G.; Cesario, F.; Borretta G. Clin. Endocrinol., 1999, 50, 321.
[49] Fahrleitner, A.; Dobnig, H.; Obernosterer, A.; Pilger, E.; Leb, G.; Weber, K.; Kudlacek, S.; Obermayer-Pietsch, B.M. J. Gen. Intern. Med,
2002, 17, 663.
[50] Weishaar, R.E.; Simpson, R.U. J. Clin. Invest., 1987, 79, 1706. 97, 1577.
[51] Weishaar, R.E.; Kim, S.M.; Saunders, D.E.; Simpson, R.U. Am. J. Physiol., 1990, 258, E134.
[52] O'Connell, T.D.; Weishaar, R.E.; Simpson, R.U. Endocrinology, 1994, 134, 899.
[53] Hochhauser, E.; Barak, J.; Kushnir, T.; Navon, G.; Meyer, M.S.; Simpson, R.U. Am. J. Physiol., 1997, 272, H1751.
Edelstein, S.; Ben Bassat, M.B.; Vidne, B.A. Angiology, 1989, 40, 300.
[54] Walters, M.R.; Ilenchuk, T.T.; Claycomb, W.C. J. Biol. Chem., 2002, 398, 1.
[55] Walters, M.R.; Wicker, D.C.; Riggle, P.C. J. Mol. Cell. Cardiol., A.E. Cir. Res., 2000, 87, 214.
[56] Merke, J.; Hofmann, W.; Goldschmidt, D.; Ritz, E. Calcif. Tissue Atherosclerosis, 2005, 186, 20.
[57] Mitsuhashi, T.; Morris Jr., R.C.; Ives, H.E. J. Clin. Invest., 1991, 90, 427.
[58] Weishaar, R.E.; Simpson, R.U. Endocr. Rev., 1989, 10, 351. 1982, 243, E483.
[59] Merke, J.; Milde, P.; Lewicka, S.; Hugel, U.; Klaus G.; Mangelsdorf, D.J.; Haussler, M.R.; Rauterberg E.W.; Ritz, E. J.Clin. Invest., 1989, 83, 1903
[60] Zehnder, D.; Bland, R.; Chana, R.S.; Wheeler, D.C.; Howie, A.J.; Williams, M.C.; Stewart, P.M.; Hewison, M. J. Am. Soc. Nephrol., 2002, 13, 621.
[61] Watson, K.E.; Abrolat, M.L.; Malone, L.L.; Hoeg, J.M.; Doherty, T.; Detrano, R.; Demer, L.L. Circulation, 1997, 96, 1755.
[62] Goodman, W.G.; Goldin, J.; Kuizon, B.D.; Yoon, C.; Gales, B; Sider, D.; Wang, Y.; Chung, J.; Emerick, A.; Greaser, L.; Elashoff, R.M.;
Salusky, I.B. New Engl. J. Med ., 2000, 342, 1478.
[63] Moe, S.M.; Duan, D.; Doehle, B.P.; O'Neill, K.D.; Chen, N.X. Kidney Int., 2003, 63, 1003.
[64] Giachelli, C.M. Z. Kardiol., 2001, 90 Suppl 3, 31.
[65] Drissi, H.; Pouliot, A.; Koolloos, C.; Stein, J.L.; Lian, J.B.; Stein, G.S.; van Wijnen, A.J. Exp. Cell. Res., 2002, 274, 323.
[66] Fraga, C.; Blanco, M.; Vigo, E.; Segura, C.; Garcia-Caballero, T.; Perez-Fernandez, R. Histochem. Cell. Biol., 2002, 117, 547.
[67] Wu, J.; Garami, M.; Cheng, T.; Gardner, D. J. Clin. Invest., 1996,
[68] Wu, J.M.; Garami, M.; Cao, L.; Li, Q.; Gardner, D.G. Am. J. Physiol., 1995, 268, E1108.
[69] Li, Q.; Gardner, D.G. J. Biol. Chem., 1994, 268, 4934.
[70] O'Connell, T.D.; Berry, J.E.; Jarvis, A.K.; Sommerman, M.J.; Simpson, R.U. Am. J. Physiol., 1997, 272, H1751.
[71] Yamamoto, T.; Kozawa, O.; Tanabe, K.; Akamatsu, S.; Matsuno, H.; Dohi, S.; Hirose, H.; Uematsu, T. Arch. Biochem. Biophys.,2002, 398, 1.
[72] Mantell, D.J.; Owens, P.E.; Bundred, N.J.; Mawer, E.B.; Canfield, A.E. Cir. Res. 2000, 87, 214.
[73] Wu-Wong, J.R.; Nakane, M.; Ma, J.; Ruan, X.; Kroener, P.E. Atherosclerosis, 2005, 186, 20.
[74] Furigay, P.; Swamy, N. J. Steroid Biochem. Med. Biol., 2004, 89-90, 427.
[75] Thomasset, M.; Perkes, C.D.; Cuisinier-Eleizes, P. Am. J. Physiol., 1982, 243, Ẽ83.
[76] Selles, J.; Boland, R. Mol. Cell. Endocrinol., 1991, 82, 229.
[77] Santillan, G.E.; Boland, R.L. J. Mol. Cell. Cardiol., 1998, 30, 225.
[78] Marinissen, M.J.; Selles, J.; Roland, R. Cell Signal, 1994, 6, 531.
[79] Santillan, G.E.; Vasquez, G.; Boland, R.L. J. Mol. Cell. Cardiol., 1999, 31, 1095.
[80] Selles, J.; Boland, R. Mol. Cell. Endocrinol., 1991, 77, 67.
[81] Shan, J.J.; Li, B.; Taniguchi, N.; Pang, P.K. Steroids, 1996, 61, 657.
[82] Selles, J.; Bellido, T.; Boland, R. J. Mol. Cell. Cardiol., 1994, 26, 1593
[83] Walentynowicz, O.; Wrzolkowa, T. Exp. Mol. Pathol., 1995, 63, 200.
[84] Taura, D.; Taura, M.; Imai, H.; Kummerow, F.A.; Tokuyasu, K.; Cho, S.B. Paroi. Arterielle, 1978, 4, 245.
[85] Sprague, S.M.; Llach, F.; Amdahl, M.; Taccetta, C.; Batlle, D. Kidney Int, 2003, 63, 1483.
© 2006 Bentham Science Publishers Ltd.
Current Medicinal Chemistry, 2006, Volume 13, Number 20, Pages 2443-2447

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