Non lens βγ-crystallin (α-subunit) and trefoil factor (β-subunit) complex, abbreviated βγ-CAT, was a novel protein isolated and purified from the Chinese red belly frog (Bombina maxima) skin, which was reported to stimulate cell migration and wound healing, induce cell detachment and cell apoptosis through nucleus translocation, and then regulate transcription factor and inflammation related cytokine. Effects of βγ-CAT on cardiovascular and blood system and its mechanisms of action remain unknown. The purposes of the following studies are to address these questions and provide novel insights into studies on some major human diseases. First, in a variety of in vivo animal models, we investigated effects of βγ-CAT on cardiovascular and blood system. The findings demonstrated that βγ-CAT exerted toxic actions on white blood cell, red blood cell, platelet, hepatic cell, renal cell and cardiovascular system, leading to reduction in counts of white blood cell, red blood cell, platelet; hypotension and arrhythmia; mild edema of cardiomyocytes; partial pulmonary congestion, infiltration of inflammatory cells into alveolar wall; water-like denaturation of hepatocytes and infiltration of inflammatory cells into portal triad; edema of renal tubule and glomerulus congestion and spleen congestion; hyperpotassaemia, increase in blood glucose; elevation in aminotransferases (ALT, AST) and LDH. We propose that the lethal causes of the experimental animals following the administration of βγ-CAT are due to cardiac failure, hyperpotassaemia and leukotoxin. Second, to investigate vascular effects of βγ-CAT, we conducted a series of experiments in rabbit aortic rings. The results indicated that βγ-CAT constricted the aortic rings in a dose-dependent manner and EC50 was 10 nM. α-adrenoreceptor antagonist (phentolamine) and serotonin receptor antagonist (S006) failed to inhibit vasoconstriction produced by βγ-CAT. It follows that the vasoconstriction effect is not mediated by α-adrenoreceptor and serotonin receptor. We conclude that hypotension is not induced by dilation of blood vessels, but by inhibition of cardiac function and that vasoconstriction effect is caused by a novel pathway. Finally, we attributed the lethal cause of βγ-CAT to cardiovascular collapse in rabbits. On the one hand, βγ-CAT decreased stroke colume of hearts following inhibition of cardiomyocytes, on the other hand, the vasoconstriction of βγ-CAT increased the afterload of hearts. So two aspects of effects lead to insufficient perfusion to major organs and death. While the mechanism (s) underlying heart failure remains unclear. So we conducted a series of experiments from Langendorff rabbit heart preparation, through endothelial cell culture to in situ immunohistochemical assay by βγ-CAT. First we investigated inotropic effects of βγ-CAT in isolated rabbit hearts using Langendorff preparation under constant head of pressure conditions and under constant flow conditions. Second we assessed the role of coronary vascular endothelial cells in the inotropic effects following removing the cells by high-K+ solution. Finally, we evaluated cytokines released by cultured endocardial endothelial cells and aortic endothelial cells stimulated by βγ-CAT and detected locations of the cytokines and apoptotic effects on both coronary endothelial cells and cardiomyocytes via immunohistochemical assay. Experiment 1 resulted in the finding that heart failure was partially due to coronary vasoconstriction. Experiment 2 resulted in the finding that heart failure caused by βγ-CAT was endothelium dependent. Experiment 3 resulted in the detection of TNF-α released by the endocardial, aortic and coronary endothelial cells andapoptosis of coronary endothelial cells induced by high concentration of βγ-CAT. In conclusion, coronary endothelial cells make greater contribution to cardiac failure induced by βγ-CAT; The cytokines released by coronary endothelial cells challenged by βγ-CAT exert actions on cardiomyocytes, reduce contractility of the cells and lead to cardiac failure.