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Invasive Hemodynamic Characterization of the Portal-hypertensive Syndrome in Cirrhotic Rats
Published on: August 1, 2018
Heat shock protein 90 is responsible for hyperdynamic circulation in portal hypertensive rats
Jian-Hua Ai1, Zhen Yang, Fa-Zu Qiu
1Center for Hepatic Surgery, Tongi Hospital, Tongi Medical College, Huazhong Science and Technological University, Wuhan, Hubei Province, China. aijh_2000@yahoo.com
Aim:
To examine the participation of HSP90 in portal hypertensive rat mesentery in vitro.
Methods:
Immunohistochemistry and Western-blot were used to examine the expression of HSP90 in mesenteric vasculature. HSP90 mRNA was detected by RT-PCR, and the role of HSP90 in hyperdynamic circulation was examined by in vitro mesenteric perfusion studies.
Results:
HSP90 was overexpressed in endothelium of mesentery vasculature in animals with experimental portal hypertension induced by partial portal vein ligation (PVL) compared with normal animals. Geldanamycin (GA), a special inhibitor of HSP90 signaling, attenuated ACh-dependent vasodilation but did not affect vasodilation in response to sodium nitroprusside in normal rats. In PVL animals, the perfused mesentery was hyporesponsive to vasoconstrictor methoxamine. GA significantly potentiated methoxamine-induced vasoconstrictor after PVL.
Conclusion:
HSP90 plays a key role in NO-dependent hyperdynamic circulation in portal hypertension and provides a novel method for future treatment of portal hypertension.
Insights
Heat shock protein 90 (HSP90) is overexpressed in portal hypertension, contributing to hyperdynamic circulation. Inhibiting HSP90 offers a potential therapeutic strategy for this condition.
Area of Science:
- Vascular biology
- Gastroenterology
- Molecular medicine
Background:
- Portal hypertension is characterized by increased pressure in the portal vein system.
- Hyperdynamic circulation is a hallmark of portal hypertension, leading to altered blood flow.
- Heat shock protein 90 (HSP90) is a molecular chaperone with diverse cellular functions.
Purpose of the Study:
- To investigate the role of HSP90 in the mesenteric vasculature of rats with experimental portal hypertension.
- To determine the functional significance of HSP90 in the hyperdynamic circulation associated with portal hypertension.
Main Methods:
- Immunohistochemistry and Western blot to assess HSP90 expression in mesenteric vasculature.
- RT-PCR to detect HSP90 mRNA levels.
- In vitro mesenteric perfusion studies to evaluate vascular responses.
Main Results:
- HSP90 was significantly overexpressed in the endothelium of mesenteric vasculature in portal hypertensive rats compared to controls.
- Geldanamycin, an HSP90 inhibitor, attenuated acetylcholine-induced vasodilation in normal rats but potentiated methoxamine-induced vasoconstriction in portal hypertensive rats.
- Mesenteric vasculature in portal hypertensive rats showed hyporesponsiveness to methoxamine, which was reversed by HSP90 inhibition.
Conclusions:
- HSP90 plays a critical role in the nitric oxide-dependent hyperdynamic circulation observed in portal hypertension.
- Targeting HSP90 presents a novel therapeutic approach for managing portal hypertension and its complications.
