| Gastric mucosal lesions, which are called portal hypertensive gastropathy (PHG) and are commonly recognized in patients with portal hypertension (PHT), are important causes of blood loss. Such lesions may be slow and insidious and lead to sudden and severe anemia, thus causing massive and sometimes fatal hemorrhaging. PHG is now recognized to be a distinct entity. Less is known about the factors responsible for its pathogenesis. Recently, angiogenesis has been recognized as a key factor for elucidating the pathophysiology of the microvessels in various fields of the medical science. Morphologic studies have shown PHG to be characterized by a marked dilatation of the mucosal and submucosal vessels without any inflammation. Thus we should ask whether an abnormality of angiogenesis is associated with a marked dilatation of the mucosal and submucosal vessels in PHG. Several investigators believe that PHT plays an etipatho- genetic role in which is associated with a splanchnic and systemic hyperdynamic circulation. It has been suggested that an overproduction of endogenous vasodilators, such asglulagon, prostacyclin, and nitric oxide (NO), could be involved in the hyperdynamic circulation. In addition, some investigators believe that the pathogenesis of PHG may be related to both active congestion and passive hyperemia, which are co-consistent with the hyperdynamic circulation of PHT, and the effects of vasodilation and angiogenesis modulated by vasodilators and growth factors involved in the pathogenesis of PHG. Heme oxygenase (HO) is an enzyme responsible for physiological heme degradation. HO metabolizes heme into carbon monoxide (CO), iron, and biliverdin. CO, like NO, is a potent vasodilator that activates soluble guanylate cyclase (sGC), leading to the generation of cyclic guanosine monophosphate (cGMP), which in turn mediates various physiological functions, such as smooth muscle relaxation and inhibition of platelet aggregation. In addition, excessive production of CO, a consequence of HO-1 overexpression, could play an important role in modulating vascular tone under different pathological situations. Thus we suspect that HO-CO may involve in the pathogenesis of PHG.Some cytokines and growth factors have been known to be modulators of angiogenesis. Among the growth factors known to accelerate angiogenesis, vascular endothelial growth factor (VEGF), also known as vascular permeability factor, and vasculotropin have as both beenfound to be strong and specifically mitogenic for endothelial cells. Although hypoxia is known to be an inducer of VEGF expression, the role of VEGF in the gastric mucosa remains to be elucidated, especially in PHG.The aims of the present study were thus to investigate whether HO-1 and VEGF appear more strongly in PHG than in the normal gastric mucosa, and whether HO-CO and VEGF play a role in the pathogenesis of PHG. This were discussed by two parts as below:Part one: The Role of Heme Oxygenase-1 in Patients with Portal Hypertensive GastropathyObjects: PHG is now recognized to be a distinct entity, which is associated with hyperdynamic circulation. It has been suggested that an overproduction of various endogenous vasodilators could be involved in this state. HO catalyzes the conversion of heme into biliverdin, iron and CO. CO, like nitric oxide, is an endogenous vasodilator that could contribute to modulation of systemic and local vascular tone. The aim of the present study was thus to investigate whether HO-1 appears more strongly in PHG than in normal gastric mucosa, and whether HO-CO pathway play a role in the pathgenesis of PHG.Methods: The specimens were obtained from the gastric mucosa of PHG and PHT without PHG and the control (CTR). The expression of HO-1 in gastric mucosal specimen was immunohistochemically assessed. Thehistological change of the gastric mucosa in PHG was detected. The relationship between PHG and esophageal varices, PHG and liver function, was also investigated. In addition, both portal venous flow (PVF) an...
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