Transcapillary Permeability and Subendothelial Distribution of Endothelial and Amniotic Fluid Insulin- Like Growth Factor Binding Proteins in the Rat Heart*

Abstract

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.

Serum Total IGF-I, Free IGF-I, and IGFBP-1 Levels in an Elderly Population

“…11 It also accelerates IGFBP-1 transport from the intravascular space through the endothelial walls of the capillaries to the target cells. 11,12 However, the associations between IGFBP-1 levels and BMI, WHR, and HDL cholesterol were independent of insulin levels. This observation suggests that a low IGFBP-1 level might be an independent marker for the metabolic disturbances, which are all associated with an increased risk of cardiovascular diseases.…”

“…9,10 IGFBP-1, one of these IGFBPS, is not restricted to the circulation and is considered to function as a transport protein that shuttles IGF-I from the intravascular space through the endothelial walls of the capillaries. 11,12 IGFBP-1 has been proposed as an acute regulator of IGF-I bioactivity and might simultaneously both inhibit and potentiate IGF-I action at different sites. 13 Recent evidence even suggests that IGFBP-1 has intrinsic mitogenic and metabolic activity.…”

O-glycosylation delays the clearance of human IGF-binding protein-6 from the circulation

“…This result is not surprising as binary IGFBP:IGF complexes are not restricted by endothelial barriers. In fact, IGFBPs may have a role in the specific targeting of IGFs to specific tissues (27)(28)(29). The organ distribution of 125 I-labelled IGFBP-3 (30) and IGFBP-6 were similar, with both IGFBPs being predominantly localised to the stomach and kidneys.…”

Animal insulin-like growth factor binding proteins and their biological functions

“…The considerable developmental changes of IGFBPs in sheep perinatal time are influenced by IGF-I availability for its biological function. Bar et al (1990) found that bovine endothelial cell binding proteins (ECBP) and amniotic fluid IGFBP-1 are able to cross rat heart capillary vessels and ECBP are localized preferentially in myocardial connective tissues in comparison with IGFBP-1 which has higher affinity to the myocardium. IGF-I like IGFBP-1 is also leaving the vascular spaces and is distributed into heart muscle during the heart perfusion by this IGF.…”