Host vascular endothelial growth factor is trophic for Plasmodium falciparum-infected red blood cells.

Plasmodium falciparum, the protozoan parasite responsible for severe malaria infection, undergoes a complex life cycle. Infected red blood cells (iRBC) sequester in host cerebral microvessels, which underlies the pathology of cerebral malaria. Using immunohistochemistry on post mortem brain samples, we demonstrated positive staining for vascular endothelial growth factor (VEGF) on iRBC. Confocal microscopy of cultured iRBC revealed accumulation of VEGF within the parasitophorous vacuole, expression of host VEGF-receptor 1 and activated VEGF-receptor 2 on the surface of iRBC, but no accumulation of VEGF receptors within the iRBC. Addition of VEGF to parasite cultures had a trophic effect on parasite growth and also partially rescued growth of drug treated parasites. Both these effects were abrogated when parasites were grown in serum-free medium, suggesting a requirement for soluble VEGF receptor. We conclude that P. falciparum iRBC can bind host VEGF-R on the erythrocyte membrane and accumulate host VEGF within the parasitophorous vacuole, which may have a trophic effect on parasite growth.

Ultrastructural changes of pancreatic islets microcirculation in nonobese diabetic (NOD) mice.

The objective of this study was to investigate the ultrastructural changes of vascular pancreatic islets using a transmission electron microscopic technique. The major ultrastructural changes of microvessel in NOD mice are indicated by the swelling and vacuolization of the endothelial cell. Swollen cells are the first noticeable lesion of the cell response in reversible degeneration that is caused by the failure of homeostatic control. Loss in endothelial cell homeostasis is primarily a marker of endothelial dysfunction that plays a key role in the pathogenesis of diabetic vascular disease by losing the control of vascular tone. Diabetes also associates with an increased generation of oxygen-derived free radicals that may impair vasodilatation through the inactivation of vasodilators. In conclusion, consistent with a hypothesis that loss of the modulatory role of the endothelium may be a critical and initiating factor in the development of diabetic vascular disease, the ultrastructural changes in this study may indicate the first sign of endothelial dysfunction. This dysfunction correlates to the relationship between diabetes and reversible lesions of vessels in NOD mice, making for a better understanding of the pathophysiology of diabetic vascular disease to set the stage for further investigation to restore endothelial dysfunction in diabetes.