TY - JOUR
T1 - Myocardial effects of VDR activators in renal failure
AU - Mizobuchi, Masahide
AU - Nakamura, Hironori
AU - Tokumoto, Masanori
AU - Finch, Jane
AU - Morrissey, Jeremiah
AU - Liapis, Helen
AU - Slatopolsky, Eduardo
N1 - Funding Information:
This research was support in part by grants from Research in Renal Diseases, Washington University School of Medicine and from Abbott Pharmaceutical . We thank the WUCKDR O’Brien Center ( P30DK079333 ) for technical assistance.
PY - 2010/7
Y1 - 2010/7
N2 - Cardiovascular complications are the leading cause of death in patients with chronic kidney disease (CKD). Traditional causes such as diabetes, smoking, aging and hypertension do not fully explain the high rate of morbidity from cardiovascular disease seen in these patients. The renin-angiotensin-aldosterone system (RAAS) regulates extracellular volume homeostasis, which contributes to blood pressure stability. Overactivity of this system is involved in the pathophysiology of cardio-renal disease. New evidence suggests that vitamin D receptor activators (VDRAs) have a suppressive effect on the RAAS; however, VDRAs also have anti-inflammatory and anti-fibrotic effects. We have demonstrated that paricalcitol, a VDRA, ameliorates left ventricular hypertrophy (LVH) in uremic rats by up-regulating the VDR, decreasing myocardial PCNA and also decreasing myocardial oxidative stress.Thus, paricalcitol can suppress the progression of LVH, myocardial and perivascular fibrosis and myocardial arterial vessel thickness presumably by up-regulating the VDR. Paricalcitol may prove to have a substantial beneficial effect on cardiac disease and its outcome in patients with CKD. Prospective randomized studies in CKD patients are necessary to confirm these results.
AB - Cardiovascular complications are the leading cause of death in patients with chronic kidney disease (CKD). Traditional causes such as diabetes, smoking, aging and hypertension do not fully explain the high rate of morbidity from cardiovascular disease seen in these patients. The renin-angiotensin-aldosterone system (RAAS) regulates extracellular volume homeostasis, which contributes to blood pressure stability. Overactivity of this system is involved in the pathophysiology of cardio-renal disease. New evidence suggests that vitamin D receptor activators (VDRAs) have a suppressive effect on the RAAS; however, VDRAs also have anti-inflammatory and anti-fibrotic effects. We have demonstrated that paricalcitol, a VDRA, ameliorates left ventricular hypertrophy (LVH) in uremic rats by up-regulating the VDR, decreasing myocardial PCNA and also decreasing myocardial oxidative stress.Thus, paricalcitol can suppress the progression of LVH, myocardial and perivascular fibrosis and myocardial arterial vessel thickness presumably by up-regulating the VDR. Paricalcitol may prove to have a substantial beneficial effect on cardiac disease and its outcome in patients with CKD. Prospective randomized studies in CKD patients are necessary to confirm these results.
KW - Cardiomyopathy
KW - Phosphorus
KW - Renal failure
KW - Vitamin D
UR - http://www.scopus.com/inward/record.url?scp=77954709540&partnerID=8YFLogxK
U2 - 10.1016/j.jsbmb.2010.03.026
DO - 10.1016/j.jsbmb.2010.03.026
M3 - Article
C2 - 20236614
AN - SCOPUS:77954709540
SN - 0960-0760
VL - 121
SP - 188
EP - 192
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
IS - 1-2
ER -