A mouse model of carcinoid syndrome and heart disease

Abstract

Abstract Introduction: 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, in order to further understand the etiology and pathophysiology of carcinoid heart disease, we developed an animal model of the carcinoid syndrome. Methods: Seventeen nude mice underwent intrasplenic injection of human pancreatic carcinoid BON cells (107), and then sacrificed 9 weeks later. Murine livers were analyzed by immunohistochemistry. Murine hearts were sectioned and the surface area of the right heart values determined. Blood also was 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 vs. 123 ± 52 ng/ml, p=0.002) when compared to the controls. Animals with carcinoid liver metastases also had a trend towards greater tricuspid valvular surface areas (242 ± 24 vs. 174 ± 25 microns, p=0.08). On histologic 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 value thickening resembling carcinoid heart disease appears to be due to exposure to factors such as serotonin secreted by carcinoid tumor cells.