| Part I: Serotonin has a mitogenic effect on human mitral VICs and this effect may be midiated by MAPK/ERK pathwayBackground:Serotonin,also called 5-HT, is a neurotransmitter,which midiate many pathological activities.However,serotonin plays an important role in human drug induced valvular disease.Our study aimed to investigate the downstream of serotonin and its 5HT2 B receptor in human mitral valvular intersiticial cells.Method:We used MTT to detect the proliferation of VICs and determind the optimal dose of 5HT. We stimulate human valvular interstitital cell with 5HT of 10μmol/L.And then we investigated the content of phospholated ERK.Results:We found 5HT can promote the proliferation of human VICs and p ERK were significantly increased after 5HT stimulation.Conclusion:Serotonin has a mitogenic effect on human mitral VICs.This effect may be midiated by MAPK/ERK pathway,but results need to be further confirmed.Part II: Long-term Serotonin administration induced valvulopathy in MiceBackground:Several drugs have been linked to cause valvulopathy in humans, including therapeutic agents for obesity, Parkinson’s disease and migraine. These drugs probably could activate serotonin 2B receptors. The purpose of this study was designed to investigate whether serotonin subcutaneous injections led to structural and compositional abnormalities of mouse valves.Methods:A total of 30 C57Bl6/J mice were prospectively enrolled: 10 control animals and serotonin groups of 20 mice that received daily subcutaneous serotonin injections(60mg/kg) for 12 weeks. Aortic valve function and histology were evaluated by echocardiography after 3 months.Results:Twelve weeks of serotonin administration resulted in thickening and compositional alteration of aortic valves in C57BL6/J mice. AV-peak press and AV-Peak flow is significantly higher in serotonin groups than control. Immunostaining for Ki-67 demonstrated an increased number of proliferating subendocardial cells. In the control group, no pathological changes were seen.Conlusion:This study provides a novel murine model of serotonin indueced valvolopathy.These findings give additional evidence for serotonin’s vital role in this disease.Part III:Long-term serotonin injection induced heart failure in mice and its possible causesBackground:Serotonin, in addition to its fundamental role as a neurotransmitter, plays a critical role in the cardiovascular system, where it is thought to be involved in the development of cardiac hypertrophy and failure.5-HT2 A,5HT2B,5HT4 receptors are all expressed in the heart and mediate a hypertrophic response to 5-HT in cardiac cells. However, their role in cardiac remodeling in vivo and the signaling pathways associated are not well understood. So we aimed to investigate the hypothesis that serotonin injection could induce heart failure in mice.Methods:A total of 30 C57Bl6/J mice were prospectively enrolled: 10 control animals and serotonin groups of 20 mice that received daily subcutaneous serotonin injections(60mg/kg) for 12 weeks. Echocardiography and histology were studied.TUNNEL staining was performed to confirm apoptosis and transmission electron microscope was ulitimated to detect the ultramicro structure disorders.Results:After 12 weeks injection of serotonin, animals got body weight lose,heart weight and body weight ratio, left ventricle end-systolic volume, left ventricle end-diastolic volume increased, left ventricular ejection faction, fractional shortening decreased,which indicates heart failure in serotoin group.Then we found there was no significant changes in left ventricular wall thickness.Masson staining showed there was no markedly fibrosis of myocytes.TUNNEL staining showed there is no significantly apotosis in serotonin group.However, transmission electron microscope results indicated fracture of sarcomere and mitochondrial swelling.And the mechanism was still to be explored.We created a novel mice model of serotonin induced dilated cardiomyopathy,and the mechanism was still to be explored.Conlusion:... |
PDF Full Text Request