Faculty Collaboration Database

A mouse model of carcinoid syndrome and heart disease. J Surg Res 2005 Jun 01;126(1):102-5

Date

05/27/2005

Pubmed ID

15916982

DOI

10.1016/j.jss.2005.01.003

Scopus ID

2-s2.0-19444370501 (requires institutional sign-in at Scopus site)   32 Citations

Abstract

BACKGROUND: Carcinoid heart disease occurs in over 65% of patients with the carcinoid syndrome and is characterized by fibrous thickening of cardiac valves, leading to heart failure. Whether serotonin is directly responsible for these cardiac abnormalities is unknown. Therefore, to further understand the etiology and pathophysiology of carcinoid heart disease, we developed an animal model of the carcinoid syndrome.

MATERIALS AND METHODS: Seventeen nude mice underwent intrasplenic injection of human pancreatic carcinoid BON cells (10(7)) and then were euthanized 9 weeks later. Murine livers were analyzed by immunohistochemistry. Murine hearts were sectioned and the surface area of the right heart valves determined. Blood was also collected and analyzed for platelet serotonin by ELISA.

RESULTS: Sixty-five percent of the mice developed gross carcinoid liver metastases demonstrated by chromogranin-A-staining lesions within the liver. Mice with carcinoid liver metastases had elevated platelet serotonin levels (1058 +/- 529 ng/ml versus 123 +/- 52 ng/ml, P = 0.002) when compared to the controls. Animals with carcinoid liver metastases also had a trend toward greater tricuspid valvular surface areas (242 +/- 24 versus 174 +/- 25 microm, P = 0.08). On histological examination, this increase in tricuspid surface area in mice with liver metastases appeared to be due to fibrosis of the valvular tissues, consistent with the pathologic findings of carcinoid heart disease.

CONCLUSIONS: Using this novel animal model of carcinoid syndrome, the tricuspid valve thickening resembling carcinoid heart disease could be due to exposure to factors such as serotonin secreted by carcinoid tumor cells.

Author List

Musunuru S, Carpenter JE, Sippel RS, Kunnimalaiyaan M, Chen H

MESH terms used to index this publication - Major topics in bold

Animals
Carcinoid Heart Disease
Disease Models, Animal
Hydroxyindoleacetic Acid
Liver Neoplasms, Experimental
Mice
Mice, Inbred BALB C
Serotonin