HYALURONATE DEGRADATION AFFECTS VENTRICULAR-FUNCTION OF THE EARLY POSTLOOPED EMBRYONIC RAT-HEART IN-SITU
HYALURONATE DEGRADATION AFFECTS VENTRICULAR-FUNCTION OF THE EARLY POSTLOOPED EMBRYONIC RAT-HEART IN-SITU
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DOI：
10.1161/01.res.74.2.244
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发表时间：
1994-02-01
影响因子：
20.1
通讯作者：
SOLURSH, M
中科院分区：
文献类型：
--
作者：
BALDWIN, HS;LLOYD, TR;SOLURSH, M
透明质酸是早期心脏细胞外基质或“心脏凝胶”的主要糖胺聚糖，但人们对其在早期心脏功能个体发育中的作用知之甚少。为探讨透明质酸降解对心功能的原位影响，从妊娠9.5天(心管形成前)开始，用大鼠血清(对照胚胎)或大鼠血清+20TRU/mL链霉菌透明质酸酶(处理胚胎)对大鼠胚胎进行体外循环培养。通过视频运动分析心球外壁和原始脑室外壁运动，分别于结扎前(培养24小时)和结扎后即刻(结扎36小时)测定心功能。在pH值为2.5的条件下，阿尔辛蓝染色证实了处理胚胎中透明质酸的降解。对照胚胎和处理胚胎的心率、周向缩短率、最大周向收缩速度和最大周向松弛速度均显著增加。尽管对照胚胎和处理胚胎在心脏成环前的心室功能差异很小，但在心脏成环后立即，透明质酸酶处理的胚胎的所有心脏性能参数都显著增加。透明质酸酶处理的胚胎没有心内膜垫，另外一组在链霉菌透明质酸酶存在下培养48-72小时的胚胎未能形成心内膜垫。这些实验是第一次(1)记录了早期心脏循环期间可量化的心室性能增加，以及(2)证明透明质酸降解导致心内膜垫形成异常，并改变了环流后心脏的心室性能。这些观察结果强调了在研究细胞外基质在正常心脏发育中的作用时，分析功能和结构的重要性。
Hyaluronic acid is the major glycosaminoglycan of the early cardiac extracellular matrix or ''cardiac jelly,'' yet little is known about its role in the ontogeny of early ventricular performance. To investigate the in situ effect of hyaluronate degradation on ventricular function, whole rat embryos were cultured in rat serum alone (control embryos) or rat serum plus 20 TRU/mL of Streptomyces hyaluronidase (treatment embryos) from gestational day 9.5 (before formation of the heart tube) through initial looping of the heart. Cardiac function was measured before looping (24 hours in culture) and immediately after looping (36 hours in culture) by video motion analysis of the external wall motion of the bulbus cordis and primitive ventricle. Degradation of hyaluronic acid in the treated embryos was confirmed by Alcian blue staining at pH 2.5. Significant increases in heart rate, circumferential shortening fraction, maximum velocity of circumferential contraction, and maximum velocity of circumferential relaxation were observed with looping in both control and treatment embryos. Although there was minimal difference in ventricular performance between control and treatment embryos before looping, there was a significant increase in all parameters of ventricular performance in the hyaluronidase-treated embryos immediately after looping of the heart. Endocardial cushions were absent in hyaluronidase-treated embryos, and an additional group of embryos cultured in the presence of Streptomyces hyaluronidase for 48 to 72 hours failed to develop endocardial cushions. These experiments are the first to (1) document a quantifiable increase in ventricular performance during early cardiac looping and (2) demonstrate that hyaluronate degradation results in abnormal endocardial cushion formation and altered ventricular performance of the post-looped heart. These observations emphasize the importance of analyzing function as well as structure in studying the role of the extracellular matrix in normal cardiac development.