title: Preventing progression of cardiac hypertrophy and development of heart failure by paricalcitol therapy in rats.
abstract: OBJECTIVE
  Vitamin D deficiency is associated with cardiac hypertrophy and heart failure, and vitamin D therapy prevents the progression of cardiac hypertrophy in animal models. Here, we examine whether vitamin D therapy prevents progression of pre-existing cardiac hypertrophy and development of heart failure.
  
  
  RESULTS
  When male Dahl salt-sensitive rats were fed a high salt (HS) diet, all rats developed cardiac hypertrophy after 5 weeks. Thereafter, rats were treated with vehicle (V), paricalcitol (PC, an active vitamin D analogue, at 200 ng, IP 3x/week), enalapril (EP, 90 μg/day), and PC + EP. All groups were continued on the HS diet and evaluated after 4 weeks of therapy. The PC and PC + EP groups, but not the V and EP only groups, showed significant prevention of progression of pre-existing cardiac hypertrophy. The signs of decompensated heart failure were evident in the vehicle-treated group; these heart failure parameters significantly improved with PC, EP or PC + EP therapy. The expression of PKCα, which is regulated by Ca(2+)and known to stimulate cardiac hypertrophy, was significantly increased in the vehicle group, and PC, EP or PC + EP effectively decreased PKCα activation. We also observed normalization of genetic alterations during progression to heart failure with PC treatment.
  
  
  CONCLUSIONS
  PC treatment resulted in both the prevention of progression of pre-existing cardiac hypertrophy and the development of heart failure, compared with improvement in progression to heart failure by EP alone. These beneficial findings in heart were associated with inhibition of PKCα activation and reversal of gene alterations.
authors.affiliation: Cardiovascular Division, Beth Israel Deaconess Medical Center, 3 Blackfan Circle, CLS 910, Boston, MA 02215, USA.
authors.forename: Soochan
authors.initials: S
authors.lastname: Bae
authors.forename: Bhargavi
authors.initials: B
authors.lastname: Yalamarti
authors.forename: Qingen
authors.initials: Q
authors.lastname: Ke
authors.forename: Sangita
authors.initials: S
authors.lastname: Choudhury
authors.forename: Hyeon
authors.initials: H
authors.lastname: Yu
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.forename: Paul
authors.initials: P
authors.lastname: Kroeger
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
authors.forename: Peter M
authors.initials: PM
authors.lastname: Kang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000517:prevention & control*; D018450:Disease Progression; D004872:Ergocalciferols / Q000627:therapeutic use*; D020869:Gene Expression Profiling; D006333:Heart Failure / Q000517:prevention & control*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D051571:Protein Kinase C-alpha / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004872:Ergocalciferols; C084656:paricalcitol; D051571:Protein Kinase C-alpha; D002118:Calcium