Transcapillary permeability and subendothelial distribution of endothelial and amniotic fluid insulin-like growth factor binding proteins in the rat heart.
Insulin-like growth factor (IGF) binding proteins (IGFBP) were purified from conditioned media of cultured bovine endothelial cells (ECBP) and from human amniotic fluid (IGFBP-1), and then labeled by radioiodination. 125I-ECBP and 125I-IGFBP-1 were perfused through isolated beating rat hearts for 1 and 5 min, and the hearts fixed and analyzed for 125I-BP content and distribution. One to 4% of the perfused 125I-ECBP and 125I-IGFBP-1 crossed the capillary boundary. The ECBPs predominantly localized as intact 125I-BP in connective tissue elements of the heart with less 125I-BP in cardiac muscle. The ratio of 125I-ECBP in connective tissue: muscle (normalized to percent vol of these compartments) was greater than or equal to 10:1. In contrast, the IGFBP-1 had a greater affinity for cardiac muscle with ratios of 125I-IGFBP-1 in connective tissue:muscle of approximately 1:2. When 125I-IGF-I, in the absence of any BPs, was perfused through the hearts approximately 3-5% left the microcirculation and was found in subendothelial tissues. 125I-IGF-I localized primarily to cardiac muscle with a distribution of connective tissue:cardiac muscle of about 1:3. The findings in the isolated perfused heart were confirmed in intact animals. After 125I-IGFBP-1 was injected into anesthetized rats and allowed to circulate for 5 min, substantial radioactivity was associated with the heart. As in the isolated heart, the IGFBP-1 preferentially localized to cardiac muscle with a connective tissue:cardiac muscle ratio of 1:3. We conclude that IGFBPs produced by endothelial cells and the IGFBP-1 contained in amniotic fluid can cross the capillary boundaries of the rat heart, and that the ECBPs preferentially localize in connective tissue elements of the myocardium, whereas IGFBP-1 predominantly localizes in cardiac muscle.
Bar
R S
RS
Department of Internal Medicine, Veterans Administration Hospital, University of Iowa, Iowa City 52246.
Clemmons
D R
DR
Boes
M
M
Busby
W H
WH
Booth
B A
BA
Dake
B L
BL
Sandra
A
A
D000653:Amniotic Fluid / Q000032:analysis*; D000818:Animals; D002199:Capillary Permeability; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D003238:Connective Tissue / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D018969:Insulin-Like Growth Factor Binding Proteins; D007457:Iodine Radioisotopes; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D007457:Iodine Radioisotopes