Global deletion of thrombospondin-1 increases cardiac and skeletal muscle capillarity and exercise capacity in mice
Global deletion of thrombospondin-1 increases cardiac and skeletal muscle capillarity and exercise capacity in mice
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DOI：
10.1113/expphysiol.2008.045989
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发表时间：
2009-06-01
影响因子：
2.7
通讯作者：
Olfert, I. Mark
中科院分区：
文献类型：
--
作者：
Malek, Moh H.;Olfert, I. Mark
血小板反应蛋白-1（TSP-1）是一种已知的血管生成抑制剂;然而，TSP-1缺失小鼠的骨骼肌表型尚未研究。本研究的目的是通过检查以下内容来比较和对比TSP-1缺失和野生型小鼠：（1）骨骼肌和心肌中的毛细血管;（2）后肢中的纤维类型组成和氧化酶活性;以及（3）TSP-1基因缺失对运动能力的影响。与野生型小鼠相比，TSP-1基因敲除小鼠的最大跑步速度增加了11%，次最大耐力跑步期间的力竭时间增加了67%。形态计量学分析显示，TSP-1基因敲除小鼠的心脏和骨骼肌中的毛细血管比野生型小鼠更高（P < 0.05），而两组之间的纤维类型组成或氧化酶活性没有差异。经胸超声心动图测量的心脏功能显示心肌收缩力没有差异，但左心室舒张末期和收缩末期尺寸更大，对应于TSP-1缺失小鼠心脏质量升高。这项研究的结果表明，TSP-1是一个重要的内源性负调节血管生成，防止过度毛细血管化的心脏和骨骼肌。仅毛细血管增加就足以增加运动能力（P < 0.05）。这些数据表明，毛细血管-肌肉界面是运动过程中限制氧运输的关键因素。
Thrombospondin-1 (TSP-1) is a known inhibitor of angiogenesis; however, a skeletal muscle phenotype of TSP-1 null mice has not been investigated. The purposes of this study were to compare and contrast TSP-1 null and wild-type mice by examining the following: (1) capillarity in the skeletal and cardiac muscles; (2) fibre type composition and oxidative enzyme activity in the hindlimb; and (3) the consequences of TSP-1 gene deletion for exercise capacity. In TSP-1 null mice, maximal running speed was 11% greater and time to exhaustion during submaximal endurance running was 67% greater compared with wild-type mice. Morphometric analyses revealed that TSP-1 null mice had higher (P < 0.05) capillarity in the heart and skeletal muscle than wild-type mice, whereas no differences for fibre type composition or oxidative enzyme activity were present between the two groups. Cardiac function, as measured by transthoracic echocardiography, revealed no difference in myocardial contractility but greater left ventricular end-diastolic and systolic dimensions, corresponding to an elevated heart mass in the TSP-1 null mice. The results of this study indicate that TSP-1 is an important endogenous negative regulator of angiogenesis that prevents excessive capillarization in the heart and skeletal muscles. The increased capillarity alone was sufficient to increase (P < 0.05) exercise capacity. These data demonstrate that the capillary-to-muscle interface is a critical factor that limits oxygen transport during exercise.