The loss or decrease in caveolin expression in the abnormally structured pulmonary vascular lesions appears to be specific for the vascular lesions since the lung tissue surrounding the lesions express caveolin normally, which likely explains the results of the Western blot protein data. It is also of interest that angiogenic growth per se does not necessarily proceed via cells that have an impaired caveolin expression, as is illustrated by the example of the liver hemangioma. However, the vascular lesions in the rat model of severe PH, which are composed of proliferating endothelial cells, also show loss or reduction in expression of caveolin 1 and 2, indicating that there are similarities between the cells involved in the pathogenesis of severe human PH and this animal model. canadian family pharmacy online
It has been previously stated that proliferating endothelial cells form the cellular basis of the plexiform lesions in severe PH. These dysfunctional endothelial cells have a central and critical role in the initiation and progression of severe PH. The loss of important cell growth control mechanisms allows for the expansion of endothelial cells, which may have acquired a selective growth advantage. Because caveolin may function as a tumor suppressor protein, and because plexiform lesion endothelial cells grow abnormally,’ we consider that loss of caveolin expression may participate in the development and/or maintenance of plexiform lesions in severe PH. In cell culture experiments, capillary-like tubule formation dramatically increased with increasing caveolin 1 levels and, conversely, decreased with down-regulation of caveolin 1 expression. The levels of endogenous caveolin 1 expression were at maximum just prior to formation of the capillary-like tubules, further supporting a critical role for caveolin 1 in endothelial cell differentiation and growth.
Not only do the endothelial cells of the plexiform lesion lack caveolin expression, but the occasional smooth-muscle cell of the plexiform lesion also demonstrates absent or decreased immunostaining for caveolin 1 and 2.