Physiological homology between Drosophila melanogaster and vertebrate cardiovascular systems.

Physiological homology between Drosophila melanogaster and vertebrate cardiovascular systems.
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DOI:
10.1242/dmm.005231
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发表时间:
2011-05
影响因子:
4.3
通讯作者:
Tearney GJ
Tearney GJ
中科院分区:
医学2区
文献类型:
--
作者:
Choma MA;Suter MJ;Vakoc BJ;Bouma BE;Tearney GJ

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与脊椎动物相比,黑腹果蝇心血管系统的生理特征仍然很差。生理表现的基本测量仍然未知。目前还不清楚在人类心血管系统中观察到的细微生理缺陷是否可以在黑腹龙身上复制。本研究采用高速染色血管造影和光学相干断层扫描技术对黑腹蝶蛹前期的心血管生理进行了表征。心脏有强烈的搏动性收缩,驱动心内、主动脉和细胞外-血管外的血淋巴流动。一些生理指标,包括体重调节的心输出量、体长调节的主动脉速度和心内剪切力,与包括人类在内的封闭脊椎动物心血管系统相似。蝶蛹前的细胞外-血管外循环驱动对流限制的流体运输。为了证明心功能障碍的同源性,我们发现,在蛹前阶段,肌钙蛋白I突变体hold -up2 (hdp2)会损害心脏收缩和舒张壁速度。心壁速度受损发生在非扩张表型与轻度抑制的分数缩短的背景下。我们还推导出接受者的工作特征曲线,表明心壁速度是一个潜在的强大的收缩期心功能障碍的鉴别器。我们的研究结果证明了生理上的同源性,并支持将黑腹龙作为复杂心血管疾病的动物模型。
The physiology of the Drosophila melanogaster cardiovascular system remains poorly characterized compared with its vertebrate counterparts. Basic measures of physiological performance remain unknown. It also is unclear whether subtle physiological defects observed in the human cardiovascular system can be reproduced in D. melanogaster. Here we characterize the cardiovascular physiology of D. melanogaster in its pre-pupal stage by using high-speed dye angiography and optical coherence tomography. The heart has vigorous pulsatile contractions that drive intracardiac, aortic and extracellular-extravascular hemolymph flow. Several physiological measures, including weight-adjusted cardiac output, body-length-adjusted aortic velocities and intracardiac shear forces, are similar to those in the closed vertebrate cardiovascular systems, including that of humans. Extracellular-extravascular flow in the pre-pupal D. melanogaster circulation drives convection-limited fluid transport. To demonstrate homology in heart dysfunction, we showed that, at the pre-pupal stage, a troponin I mutant, held-up2 (hdp2), has impaired systolic and diastolic heart wall velocities. Impaired heart wall velocities occur in the context of a non-dilated phenotype with a mildly depressed fractional shortening. We additionally derive receiver operating characteristic curves showing that heart wall velocity is a potentially powerful discriminator of systolic heart dysfunction. Our results demonstrate physiological homology and support the use of D. melanogaster as an animal model of complex cardiovascular disease.
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