Gutkowska Jolanta, Miszkurka Malgorzata, Danalache Bogdan, Gassanov Natig, Wang Donghao, Jankowski Marek
Centre de Recherche CHUM, Hôtel-Dieu, 3850 St-Urbain, Montréal, QC, Canada H2W 1T7.
Am J Physiol Heart Circ Physiol. 2007 Oct;293(4):H2262-70. doi: 10.1152/ajpheart.01320.2006. Epub 2007 Jul 13.
Since the neurohypophyseal hormone 8-arginine vasopressin (AVP) is involved in cardiovascular tissue hypertrophy and myocyte differentiation, it is possible that local AVP plays a role in heart maturation. AVP-specific RIA, RT-PCR, and immunoblot measurement of AVP receptors (VR) were used to investigate heart tissues from newborn and adult rats. To test AVP's role in differentiation and specialization into ventricle-like cardiomyocytes, we studied GFP-P19Cl6 stem cells, which express green fluorescence protein (GFP) reporter under transcriptional control of the myosin light chain-2v promoter. VR(1) transcripts and proteins were higher in adult than in newborn rat hearts. In contrast, VR(2) increased from postnatal day 1 to 5 and was barely detected in the adult rat heart. In cardiomyocytes expressing troponin C, immunofluorescence revealed VR(2) and VR(1). Intracellular cAMP increased 6.5- and 8.9-fold in response to the selective VR(2) agonist 1-desamino-8-D-AVP (DDAVP) after 1 and 24 h, respectively. Cardiac AVP was high in 1- and 5-day-old (330 +/- 26 and 276 +/- 53 pg/mg protein, respectively) but low in 66-day-old (98 +/- 15 pg/mg protein) rats. AVP immunostaining was detected in the tunica adventitia and endothelium of the coronary vessels. The possible role of AVP in cardiomyogenesis was indicated by DDAVP-AVP-dependent differentiation of GFP-P19Cl6 stem cells into contracting cells displaying GATA-4, a cardiac-specific marker, and ventricle-specific myosin light chain. Together, it is suggested that the AVP system is implicated in postnatal cardiac maturation.
由于神经垂体激素8-精氨酸加压素（AVP）参与心血管组织肥大和心肌细胞分化，因此局部AVP可能在心脏成熟过程中发挥作用。采用AVP特异性放射免疫分析（RIA）、逆转录-聚合酶链反应（RT-PCR）以及AVP受体（VR）的免疫印迹检测方法，对新生大鼠和成年大鼠的心脏组织进行研究。为了检测AVP在向心室样心肌细胞分化和特化过程中的作用，我们研究了绿色荧光蛋白（GFP）-P19Cl6干细胞，该细胞在肌球蛋白轻链-2v启动子的转录控制下表达绿色荧光蛋白（GFP）报告基因。成年大鼠心脏中VR(1)的转录本和蛋白水平高于新生大鼠心脏。相比之下，VR(2)从出生后第1天到第5天增加，在成年大鼠心脏中几乎检测不到。在表达肌钙蛋白C的心肌细胞中，免疫荧光显示存在VR(2)和VR(1)。分别在1小时和24小时后，选择性VR(2)激动剂1-去氨基-8-D-精氨酸加压素（DDAVP）可使细胞内环磷酸腺苷（cAMP）分别增加6.5倍和8.9倍。1日龄和5日龄大鼠心脏中的AVP含量较高（分别为330±26和276±53 pg/mg蛋白），而66日龄大鼠心脏中的AVP含量较低（98±15 pg/mg蛋白）。在冠状血管的外膜和内皮中检测到AVP免疫染色。DDAVP-AVP依赖性地将GFP-P19Cl6干细胞分化为显示心脏特异性标志物GATA-4和心室特异性肌球蛋白轻链的收缩细胞，这表明AVP在心肌发生中可能发挥作用。综上所述，提示AVP系统与出生后心脏成熟有关。
