Cellular pathophysiology of portal hypertension and prospects for management with gene therapy.
In summary, regulation of sinusoidal blood flow in normal and injured liver involves structural, cellular, and humoral components. Available data suggest that stellate cells, resident perisinusoidal mesenchymal cells with a histologic orientation in the sinusoid analogous to [figure: see text] vasoregulatory pericytes, modulate sinusoidal blood flow. This regulation by stellate cells is most evident in the context of liver injury but may apply also to the normal liver. The endothelin and NO systems are important in modulating stellate cell contractility, and their degree of equilibrium is significant in determining the level of local intrahepatic resistance, especially in the injured liver. Manipulation of either or both of these systems is feasible and effective in experimental models. Such findings have obvious clinical implications and are expected to set the [figure: see text] stage for novel gene therapy approaches for treatment of patients with portal hypertension.
Rockey
D C
DC
Departments of Medicine and Cell Biology, Duke University Medical Center, Durham, North Carolina, USA. dcrockey@acpub.duke.edu
D016232:Endothelins / Q000627:therapeutic use; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D006975:Hypertension, Portal / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D009569:Nitric Oxide / Q000627:therapeutic use
D016232:Endothelins; D009569:Nitric Oxide