Correlated Endothelial Caveolin Overexpression and Increased Transcytosis in Experimental Diabetes

Abstract

S U M M A R Y We investigated the mechanism by which diabetes renders the capillary endothelium more permeable to macromolecules in the lungs of short-term diabetic rats. We used quantitative immunocytochemistry (ICC) to comparatively assess the permeability of alveolar capillaries to serum albumin in diabetic and normoglycemic animals. The effect of diabetes on the population of endothelial caveolae was evaluated by morphometry and by ICC and immunochemical quantification of the amount of caveolin in the whole cell or associated with the purified endothelial plasma membrane. A net increase in the amount of serum albumin taken up by the plasmalemmal vesicles of alveolar endothelial cells and transported to the interstitium was documented in diabetic animals. Interendothelial junctions were not permeated by albumin molecules. The alveolar endothelial cells of hyperglycemic rats contain more caveolae (1.3-fold), accounting for a larger (1.5-fold) fraction of the endothelial volume than those of normal animals. The hypertrophy of the caveolar compartment is accompanied by overexpression of endothelial caveolin 1. Although the aggregated thickness of the endothelial and alveolar epithelium basement membranes increases in diabetes (1.3-fold), the porosity of this structure appears to be unchanged. Capillary hyperpermeability to plasma macromolecules recorded in the early phase of diabetes is explained by an intensification of transendothelial vesicular transport and not by the destabilization of the interendothelial junctions.

Molecular determinants of endothelial transcytosis and their role in endothelial permeability

“…This result is consistent with the existence in different cell lines of cytosolic pools of caveolin-1, which are not engaged in caveolae formation (158,217,238). Likewise, in several pathological conditions, such as diabetes, the upregulation of caveolin-1 was accompanied by hypertrophy of the caveolar compartment (139). The complexity of in vivo situation on one hand and the complexity of the pathological condition on the other hand make the correlation between the caveolin-1 expression and caveolae number a controversial issue.…”

Efficient Transduction of Vascular Endothelial Cells with Recombinant Adeno-Associated Virus Serotype 1 and 5 Vectors

“…However, limited progress has thus far been made in gene therapy strategies for endothelial cells. Transcytosis, regular replacement of endothelial cells and an abundance of extracellular matrix are but a few factors that limit the efficacy of transduction in endothelial cells (Pajusola et al, 2002;Pascariu et al, 2004).…”

Role of NF-κB-dependent Caveolin-1 Expression in the Mechanism of Increased Endothelial Permeability Induced by Lipopolysaccharide

“…Cav-1-null mice, lacking caveolae (9), showed defective albumin transcytosis (10). In an experimental model of diabetes, increased Cav-1 expression in endothelial cells was associated with increased transcytosis of albumin (11). LPS was shown to induce the expression of Cav-1 in endothelial cells (12) and murine macrophages (13,14); however, the mechanisms of the response and its consequences in regulating endothelial barrier function are not clear.…”