The mass of healthy adult tissues is stable and their vasculature is quiescent, but this equilibrium is disrupted under certain physiological or pathological situations. There is an emerging concept indicating that these trophic changes may be initiated by modifications of the vasculature. In the current study, we documented over a period of 14 d the serial alterations occurring in both endocrine and endothelial compartments during adrenal atrophy induced by ACTH suppression in mice. After dexamethasone perfusion, a rapid fall of plasmatic ACTH and corticosterone concentrations was observed within the first 24 h. During the first 4 d of treatment, adrenal weight and adrenal cortex cellularity decreased rapidly. This was correlated with an inhibition of cell proliferation and a massive induction of endocrine cell apoptosis. Between d 4 and d 14, a slower but sustained decay of adrenal cortex size and cellularity was observed. This second phase was associated with progressive loss of vascular endothelial growth factor protein expression in the endocrine cells and regression of the vascular network. These data support the concept that ACTH controls adrenal cortex trophicity through a dual mechanism involving its antiapoptotic effect on endocrine cells and its indirect vascular endothelial growth factor-mediated action on endothelial cells.

With the aim to study how to modulate the specific endothelial cell patterning and responses on biomaterials surfaces, bioactive microarrays were developed and validated for specific cell patterning. These microarrays were made of low-fouling surfaces, that prevent nonspecific cell adhesion, bearing bioactive molecules at given known locations by presenting specific ligands to cell receptors. Arrays of bioactive molecules (RGD, REDV, and SVVYGLR sequences and vascular endothelial growth factor (VEGF)) were immobilized on a carboxy-methyl-dextran low-fouling surface and were exposed to human endothelial cells and fibroblasts to screen for the effect of bioactive spot molecular composition on cell adhesion. Endothelial cells only were sensitive to RGD peptide co-immobilized with REDV or SVVYGLR sequences: they induced a reduction in cell spreading and a loss of actin stress fibers. RGD co-immobilized with VEGF also resulted in the reorganization of actin filaments and focal points in endothelial cells. Combination of RGD with these endothelial cell-selective biomolecules did not elicit a strong adhesion phenotype but rather one characteristic of migrating cells.

To control protein adsorption on surfaces, low-fouling polymer coatings such as poly(ethylene oxide) (PEG or PEO) and polysaccharides are used. Their ability to resist protein adsorption is related to the layer structure, hence the immobilization mode. A polymer array technology was developed to study the structural diversity of carboxymethyl dextran (CMD) layers, whose immobilization conditions were varied. CMD arrays were analyzed by X-ray photoelectron spectroscopy (XPS) and by atomic force microscopy (AFM) colloidal probe force measurements. Serum protein adsorption was studied directly on the CMD arrays using surface plasmon resonance (SPR) microscopy. Physicochemical characterization revealed that pinning density regulates surface coverage and the amount of adsorbed molecules, and that salt concentration influences the surface structure of the charged polymer, forming extended or short layers. Protein adsorption experiments from serum showed that repulsive CMD layers are dense, with extended flexible chains. The present study underlines the usefulness of polymer arrays to study structural diversity of thin graft layers and to relate their physicochemical properties to their resistance to nonspecific protein adsorption.

The adrenal cortex is a highly vascularized endocrine tissue. A dense network of blood capillaries centripetally irrigates the adrenal gland, allowing every endocrine cell to be in contact with an endothelial cell. The pituitary hormone ACTH controls the coordinated development of the vasculature and the endocrine tissue mass. This suggests that paracrine secretions between steroidogenic adrenocytes and capillary endothelial cells participate in the control of adrenocortical homeostasis. Besides its effect on the vascular tone of arteries, ACTH induces the expression of the angiogenic cytokine VEGF-A (vascular endothelial growth factor-A) in primary cultures of adrenocortical cells. This growth factor is a specific mitogen for endothelial cells and is likely to mediate the hormonal control of adrenocortical vascularization through a paracrine mechanism. The newly discovered angiogenic factor EG-VEGF (endocrine-gland-derived vascular endothelial growth factor), the expression of which is restricted to endocrine glands and which is preferentially mitogenic for endocrine tissue-derived endothelial cells, is another candidate mediator of great potential interest.