Differential calcium handling in two canine models of right ventricular pressure overload.
Differential calcium handling in two canine models of right ventricular pressure overload.
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DOI：
10.1016/j.jss.2012.04.066
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发表时间：
2012-12
期刊：
影响因子：
--
通讯作者：
Yamada KA
中科院分区：
文献类型：
--
作者：
Moon MR;Aziz A;Lee AM;Moon CJ;Okada S;Kanter EM;Yamada KA
本研究的目的是表征右心房（RA）和心室（RV） Ca2+处理蛋白的差异分子变化，这是由于右心室压力过载和肥大导致的两种常见但不同的肺动脉高压模型，脱氢单罗塔碱（DMCT）毒性和肺动脉（PA）带。18只犬行胸骨切开术，分为四组：DMCT毒性（n=5）， 2.轻度PA束带超过10周，与DMCT的右心室压力升高相匹配（n=5）， 3.进行性PA束带产生严重的右心室过载（n=4）， 4.仅开胸术（n=4）。右心室：DMCT时，肌浆网Ca2+- atp酶（SERCA）或磷蛋白（PLB）没有变化，但丝氨酸-16磷酸化PLB有下调的趋势（p(Ser-16)PLB） （p = 0.07）。同样，在轻度PA带化中，SERCA或PLB没有变化，但p(Ser-16)PLB下调了74% （p < 0.001）。严重PA带化时，PLB无变化，但SERCA下降57%，p(Ser-16)PLB下降67% （p < 0.001）。右心房：DMCT无明显改变。在轻度和重度PA分级中，p(Ser-16)PLB下降（p < 0.001），但SERCA和PLB没有变化。Ca2+处理蛋白的扰动取决于右心室压力过载的程度和用于模拟肺动脉高压的右心室效应的模型，与心室相比，在心房中是相似的，但变钝了。
The purpose of this study investigation was to characterize differential right atrial (RA) and ventricular (RV) molecular changes in Ca2+-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. Eighteen dogs underwent sternotomy with four groups: 1.) DMCT toxicity (n=5), 2.) mild PA banding over 10 weeks 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). Right Ventricle: With DMCT, there was no change in sarcoplasmic reticulum Ca2+-ATPase (SERCA) or phospholamban (PLB), but a trend to downregulation 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 downregulated 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). 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. 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 and are similar, but blunted, in the atrium compared to the ventricle.
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