Torrado Mario, López Eduardo, Centeno Alberto, Castro-Beiras Alfonso, Mikhailov Alexander T
Developmental Biology Unit, Institute of Health Sciences, University of La Coruña, Campus de Oza, Building 'El Fortín', Las Xubias s/n, La Coruña 15006, Spain.
Eur J Heart Fail. 2004 Mar 1;6(2):161-72. doi: 10.1016/j.ejheart.2003.11.004.
Cardiac ankyrin repeat protein (CARP), whose expression is down-regulated in response to doxorubicin (Dox) in vitro, has been proposed to be a marker of experimentally-induced cardiac hypertrophy in rodent models. In piglets, the rapid hypertrophy rate of the left ventricle (LV) as compared to that of the right ventricle (RV) represents a natural model of asymmetric ventricular enlargement. We tested whether CARP expression correlates with postnatal ventricular hypertrophy and to what extent CARP can be sensitive to Dox treatment in vivo.
CARP mRNA and protein levels were quantified (by Northern blot hybridization, semi-quantitative RT-PCR and Western blot) in the piglet heart, both during early postnatal development and upon Dox-induced cardiomyopathy (Dox-CM).
The study revealed: (1) significantly augmented CARP mRNA and protein levels in the LV compared to the RV resulting in left vs. right asymmetry in ventricular CARP expression throughout early postnatal development; (2) dose- and chamber-dependent CARP mRNA and protein enrichment in ventricular myocardium in response to Dox; and (3) abolishment of asymmetric patterns of ventricular CARP expression at heart failure resulting from Dox-CM.
(1) CARP is differentially regulated in the LV and RV during both postnatal development and disease; and (2) monitoring of ventricular CARP expression patterns can be used for further analysis of transition from compensated to overt heart failure.
心肌锚蛋白重复蛋白（CARP）在体外对阿霉素（Dox）反应时表达下调，已被认为是啮齿动物模型中实验性诱导心肌肥大的一个标志物。在仔猪中，与右心室（RV）相比，左心室（LV）的快速肥大率代表了一种不对称心室扩大的天然模型。我们测试了CARP表达是否与出生后心室肥大相关，以及CARP在体内对Dox治疗的敏感程度。
在仔猪出生后早期发育期间以及Dox诱导的心肌病（Dox-CM）发生时，通过Northern印迹杂交、半定量RT-PCR和Western印迹对仔猪心脏中的CARP mRNA和蛋白水平进行定量。
该研究揭示：（1）与右心室相比，左心室中CARP mRNA和蛋白水平显著增加，导致在整个出生后早期发育过程中心室CARP表达出现左右不对称；（2）响应Dox时，心室心肌中CARP mRNA和蛋白富集呈剂量和腔室依赖性；（3）Dox-CM导致心力衰竭时，心室CARP表达的不对称模式消失。
（1）在出生后发育和疾病过程中，CARP在左心室和右心室中受到不同调节；（2）监测心室CARP表达模式可用于进一步分析从代偿性心力衰竭向显性心力衰竭的转变。
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