Tissue endostatin correlates inversely with capillary network in rat heart and skeletal muscles

被引:27
作者
Gu J.-W. [1 ]
Shparago M. [1 ]
Tan W. [1 ]
Bailey A.P. [1 ]
机构
[1] Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216-4505
基金
美国国家卫生研究院;
关键词
Capillary density; Endostatin; Heart; Metabolic activity; Skeletal muscle; VEGF;
D O I
10.1007/s10456-006-9035-z
中图分类号
学科分类号
摘要
The role of angiostatic factors, including endostatin, in regulating physiological angiogenesis is poorly understood. We used normal adult rats under physiological resting conditions to examine the relationship between tissue endostatin, VEGF, and capillary density (CD) in the heart (high metabolic activity) versus the skeletal muscle (relatively low metabolic activity). The heart (left ventricle, LV) and skeletal muscle (anterior tibialis, AT) were dissected from 12-week-old male Sprague-Dawley rats. Transverse cryosections of LV and AT were stained with FITC-conjugated GS-I-lectin. CD was determined by analysis of randomly acquired digital images of the cryosections using Optimas software. Tissue protein levels of endostatin and VEGF were determined by ELISA assays. Tissue endostatin levels were lower in the LV and higher in the AT (135 ± 39 vs. 663 ± 114 pg/mg) and VEGF levels were higher in the LV and lower in the AT (41 ± 3 vs. 27 ± 4 pg/mg), respectively (n = 7, P < 0.01). CD in LV and AT were 3632 ± 428 and 437 ± 44/mm2, respectively (P < 0.01). We demonstrated that an 8.3-fold greater capillary density is related to a 4.9-fold lower level of tissue endostatin and a 1.5-fold higher level of tissue VEGF in the heart (LV) versus the skeletal muscle (AT) of normal rats under physiological resting conditions. Also, exercise training increased capillary density, decreased tissue endostatin and increased tissue VEGF in the skeletal muscle (AT). These findings suggest that tissue endostatin content correlates inversely with capillary network in the muscle tissues with different metabolic activity, and that tissue endostatin may play a very important role in the metabolic control of angiogenesis under physiological conditions. © Springer Science+Business Media B.V. 2006.
引用
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页码:93 / 99
页数:6
相关论文
共 22 条
[11]  
Hoppeler H., Kayer S.R., Capillary and oxidative capacity of muscles, News Physiol Sci, 3, pp. 113-116, (1988)
[12]  
Mall G., Schkora I., Mattfeldt T., Bodle R., Dipyridamole-induced neoformation of capillaries in the rat heart, Lab Invest, 57, pp. 86-93, (1987)
[13]  
Gu J.W., Fortepiani L., Reckelhoff J., Et al., Increased expression of vascular endothelial growth factor and capillary density in hearts of Spontaneously Hypertensive Rats, Microcirculation, 11, pp. 689-697, (2004)
[14]  
Folkman J., Angiogenesis in cancer, vascular, rheumatoid, and other disease, Nat Med, 1, pp. 27-31, (1995)
[15]  
Panchal V.R., Rehman J., Nguyen A.T., Et al., Reduced pericardial levels of endostatin correlated with collateral development in patients with ischemic heart disease, J Am Coll Cariol, 43, pp. 1383-1387, (2004)
[16]  
Bhutto I.A., Kim S.Y., McLeod D.S., Et al., Localization of collagen XVII and the endostatin portion of collagen XVIII in aged human control eyes and eyes with age-related macular degeneration, Investigative Ophthalmol Visual Sci, 45, pp. 1544-1552, (2004)
[17]  
Sund M., Hamano Y., Sugimoto H., Et al., Function of endogenous inhibitiors of angiogenesis as endothelium-specific tumor suppressors, PNAS, 102, pp. 2934-2939, (2005)
[18]  
Abdollahi A., Hahnfeldt P., Maercker C., Et al., Endostatin's antiangiogenic signaling network, Mol Cell, 13, pp. 649-663, (2004)
[19]  
Yamaguchi N., Anand-Apte B., Lee M., Et al., Endostatin inhibits VEGF-induced endothelial cell migration and tumor growth independently of zinc binding, EMBO J, 18, pp. 4414-4432, (1999)
[20]  
Heljasvaara R., Nyberg P., Luostarinen J., Et al., Generation of biologically active endostatin fragments from human collagen XVIII by distinct matrix metalloproteases, Exp Cell Res, 307, pp. 292-304, (2005)