Differential calcium handling in two canine models of right ventricular pressure overload

Marc R. Moon, Abdulhameed Aziz, Anson M. Lee, Cynthia J. Moon, Shoichi Okada, Evelyn M. Kanter, Kathryn A. Yamada

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Background: The purpose of this investigation was to characterize differential right atrial (RA) and ventricular (RV) molecular changes in Ca 2+-handling proteins consequent to RV pressure overload and hypertrophy in two common, yet distinct models of pulmonary hypertension: dehydromonocrotaline (DMCT) toxicity and pulmonary artery (PA) banding. Methods: A total of 18 dogs underwent sternotomy in four groups: (1) DMCT toxicity (n = 5), (2) mild PA banding over 10 wk to match the RV pressure rise with DMCT (n = 5); (3) progressive PA banding to generate severe RV overload (n = 4); and (4) sternotomy only (n = 4). Results: In the right ventricle, with DMCT, there was no change in sarcoplasmic reticulum Ca2+-ATPase (SERCA) or phospholamban (PLB), but we saw a trend toward down-regulation of phosphorylated PLB at serine-16 (p[Ser-16]PLB) (P = 0.07). Similarly, with mild PA banding, there was no change in SERCA or PLB, but p(Ser-16)PLB was down-regulated by 74% (P < 0.001). With severe PA banding, there was no change in PLB, but SERCA fell by 57% and p(Ser-16)PLB fell by 67% (P < 0.001). In the right atrium, with DMCT, there were no significant changes. With both mild and severe PA banding, p(Ser-16)PLB fell (P < 0.001), but SERCA and PLB did not change. Conclusions: Perturbations in Ca2+-handling proteins depend on the degree of RV pressure overload and the model used to mimic the RV effects of pulmonary hypertension. They are similar, but blunted, in the atrium compared with the ventricle.

Original languageEnglish
Pages (from-to)554-562
Number of pages9
JournalJournal of Surgical Research
Volume178
Issue number2
DOIs
StatePublished - Dec 2012

Keywords

  • Calcium-handling proteins
  • Chronic pulmonary hypertension
  • Dehydromonocrotaline
  • Pulmonary banding
  • Right atrium
  • Right ventricular hypertrophy

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