2015 ACVIM Forum Research Abstract Program

Down-regulated gene expression, encoding sarcoplasmic reticulum (SR) Ca 2 + -ATPase and its regulatory proteins such as SR Ca 2 + -ATPase isoform 2a (SERCA2a) and phospholamban (PLN), plays a crucial role in myocardial decompensation due to the impairment of intracellular Ca 2+ cycling.It has been reported that SERCA2a and PLN expressed in peripheral blood mononuclear cells (PBMC) not only are translatable to the myocardial setting, but also significantly decrease in dogs with degenerative mitral valve disease.The aim of this study is to clarify how effectively the target genes reflect hemodynamic overload, a primary determinant of myocardial distress.Healthy laboratory beagles (n = 24), very young dogs with patent ductus of arteriosus (PDA; n = 8) and with pulmonic stenosis (PS; n = 5) were enrolled in this study.None of patients have been treated previously with cardiovascular medication.All PDA patients were in subclinical stage, whereas PS patients had severe stenosis.The mRNA levels of SERCA2a and PLN in PBMC were evaluated before and one week after surgical intervention with using quantitative real-time PCR.Plasma concentration of NT-proBNP was also measured as a reference of cardiac biomarkers.Compared with control group, the fold-changes of the both target genes were significantly low in PDA (0.50 AE 0.17 for SER-CA2a and 0.41 AE 0.21 for PLN) as well as in PS (0.47 AE 0.20 for SERCA2a and 0.35 AE 0.10 for PLN).In paired comparison between pre-and post-operation, their expression levels significantly increased one week after surgical correction in both PDA (0.74 AE 0.22 for SERCA2a and 0.68 AE 0.24 for PLN) and PS (0.74 AE 0.18 for SERCA2a and 0.65 AE 0.20 for PLN).Meanwhile, plasma levels of NT-proBNP between before and after surgery were not different in both PDA (before surgery, 761.0 AE 579.2 pmol/L; one week after surgery, 679.9 AE 437.2 pmol/L) and PS (before surgery, 867.2 AE 560.2 pmol/L; one week after surgery, 863.4 AE 523.1 pmol/L).Additionally, the expression levels of SER-CA2a and PLN were significantly correlated to hemodynamic indices, such as fractional shortening and LA/Ao ratio in PDA, and peak pressure gradient in PS (P < 0.05).Furthermore, receiveroperating characteristic analysis showed high values of the area under the curve in SERCA2a (0.95 AE 0.04 in PDA; 0.95 AE 0.04 in PS) and PLN (1.00 AE 0.0 in PDA; 0.98 AE 0.03 in PS).To conclude, SERCA2a and PLN expressed in the PBMC may be effectively able to reflect myocardial distress determined by hemodynamic change as cardiac biomarkers.