Thrombospondin-1 and CD47 regulate blood pressure and cardiac responses to vasoactive stress.
Thrombospondin-1 and CD47 regulate blood pressure and cardiac responses to vasoactive stress.
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DOI：
10.1016/j.matbio.2009.01.002
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
Roberts DD
中科院分区：
文献类型：
--
作者：
Isenberg JS;Qin Y;Maxhimer JB;Sipes JM;Despres D;Schnermann J;Frazier WA;Roberts DD
一氧化氮（NO）通过调节血管张力局部调节血管阻力和血压。血小板反应蛋白-1信号通过其受体CD 47局部限制NO松弛血管平滑肌细胞和增加缺血组织局部血流量的能力。为了确定血小板反应蛋白-1是否在中枢心血管生理学中发挥更广泛的作用，我们研究了缺乏血小板反应蛋白-1或CD 47的小鼠的血管活性应激反应。缺乏血小板反应蛋白-1的小鼠表现出与活动相关的心率、中心舒张压和平均动脉压增加以及脉压持续降低。CD 47缺陷型小鼠具有正常的中枢脉压，但静息外周血压升高。两种无效小鼠均显示外周血压的过度降低和心输出量和射血分数的增加以响应NO。自主神经阻滞还在清醒的血小板反应蛋白-1无效和CD 47无效小鼠中诱导过度的水肿反应。这两种无效小鼠对异氟烷表现出更大的肿胀反应，并且在异氟烷麻醉下的自主神经阻断导致血小板反应蛋白-1无效小鼠的过早死亡。相反，在血小板反应蛋白-1缺失小鼠中，对肾上腺素的高血压反应减弱。因此，基质细胞蛋白血小板反应蛋白-1及其受体CD 47作为血压的急性生理调节剂，并发挥血管加压活性，以维持应激下的整体血液动力学。
Nitric oxide (NO) locally regulates vascular resistance and blood pressure by modulating blood vessel tone. Thrombospondin-1 signaling via its receptor CD47 locally limits the ability of NO to relax vascular smooth muscle cells and increase regional blood flow in ischemic tissues. To determine whether thrombospondin-1 plays a broader role in central cardiovascular physiology, we examined vasoactive stress responses in mice lacking thrombospondin-1 or CD47. Mice lacking thrombospondin-1 exhibit activity-associated increases in heart rate, central diastolic and mean arterial blood pressure and a constant decrease in pulse pressure. CD47-deficient mice have normal central pulse pressure but elevated resting peripheral blood pressure. Both null mice show exaggerated decreases in peripheral blood pressure and increased cardiac output and ejection fraction in response to NO. Autonomic blockade also induces exaggerated hypotensive responses in awake thrombospondin-1 null and CD47 null mice. Both null mice exhibit a greater hypotensive response to isoflurane, and autonomic blockage under isoflurane anesthesia leads to premature death of thrombospondin-1 null mice. Conversely, the hypertensive response to epinephrine is attenuated in thrombospondin-1 null mice. Thus, the matricellular protein thrombospondin-1 and its receptor CD47 serve as acute physiological regulators of blood pressure and exert a vasopressor activity to maintain global hemodynamics under stress.
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DOI：
10.1083/jcb.200211041
发表时间：
2003-03-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mullershausen F;Friebe A;Feil R;Thompson WJ;Hofmann F;Koesling D
通讯作者：
Koesling D
影响因子：
20.1
作者：
Isenberg, Jeff S.;Romeo, Martin J.;Roberts, David D.
通讯作者：
Roberts, David D.
影响因子：
--
作者：
Emmanouil, Dimitris E;Quock, Raymond M
通讯作者：
Quock, Raymond M
影响因子：
37.8
作者：
Chen, DH;Asahara, T;Andrés, V
通讯作者：
Andrés, V
影响因子：
24
作者：
Inglessis, I;Shin, JT;Semigran, MJ
通讯作者：
Semigran, MJ