CC-chemokine receptor 7 and its ligand CCL 19 promote mitral valve interstitial cell migration and repair

The effect of CC-chemokine receptor 7 （CCR7） and CC-chemokine ligand 19 （CCL19） on rheumatic mitral ste- nosis is unknown. This study aimed to explore the roles of CCR7 and CCL19 in rheumatic mitral stenosis by mea- suring the expression of CCR7 and CCL19 in human mitral valves from rheumatic mitral stenosis patients. Additionally, we examined their effects on human mitral valve interstitial cells （hMVICs） proliferation, apoptosis and wound repair. CCR7 and CCL19 expression was measured in the mitral valves from rheumatic mitral stenosis patients （n= 10） and compared to normal mitral valves （n=5）. CCR7 was measured in cultured hMVICs from rheu- matic mitral stenosis patients and normal donors by RT-PCR and immunofluorescence. The cells were also treated with exogenous CCL19, and the effects on wound healing, proliferation and apoptosis were assayed. In the rheu- matic mitral valves, valve interstitial cells expressed CCR7, while mononuclear cells and the endothelium expressed CCL19. Healthy mitral valves did not stain positive for CCR7 or CCL19. CCR7 was also detected in cultured rheu- matic hMVICs or in normal hMVICs treated with CCL19. In a wound healing experiment, wound closure rates of both rheumatic and normal hMVICs were significantly accelerated by CCL19. These effects were abrogated by a CCR7 neutralizing antibody. The CCR7/CCL19 axis did not influence the proliferation or apoptosis of hMVICs, indicating that wound healing was due to increased migration rates rather than increased proliferation. In conclu- sion, CCR7 and CCL19 were expressed in rheumatic mitral valves. The CCR7/CCL19 axis may regulate remodel- ing of rheumatic valve injury through promoting migratory ability of hMVICs.

The cardioprotection induced by lipopolysaccharide involves phosphoinositide 3-kinase/Akt and high mobility group box 1 pathways

Objective： The mechanisms by which lipopolysaccharide （LPS） pretreatment induces cardioprotection following ischaemia/reperfusion （I/R） have not been fully elucidated. We hypothesized that activation of phosphoinositide 3-kinase （PI3K）/Akt and high mobility group box 1 （HMGBxl） signaling plays an important role in LPS-induced cardioprotection. Methods： In in vivo experiments, age- and weight- matched male C57BL/10Sc wild type mice were pretreated with LPS before ligation of the left anterior descending coronary followed by reperfusion. Infarction size was examined by triphenyltetrazolium chloride （TTC） staining. Akt, phospho-Akt, and HMGBxl were assessed by immunoblotting with appropriate primary antibodies. In situ cardiac myocyte apop- tosis was examined by the TdT-mediated dUTP nick-end labeling （TUNEL） assay. In an in vitro study, rat cardiac myoblasts （H9c2） were subdivided into two groups, and only one was pretreated with LPS. After pretreatment, the cells were transferred into a hypoxic chamber under 0.5% 02. Levels of HMGBxl were assessed by immunoblot. Results： In the in vivo experiment, pretreatment with LPS reduced the at risk infarct size by 70.6% and the left ventricle infarct size by 64.93% respectively. Pretreatment with LPS also reduced cardiac myocytes apoptosis by 39.1% after ischemia and reperfusion. The mechanisms of LPS induced cardioprotection involved increasing PI3K/Akt activity and decreasing expression of HMGBxl. In the in vitro study, pretreatment with LPS reduced the level of HMGBxl in H9c2 cell cytoplasm following hypoxia. Conclusion： The results suggest that the cardioprotection following I/R induced by LPS pretreatment involves PI3K/Akt and HMGBxl pathways.

Familial cardiac myxoma with multifocal recurrences:a case report and review of the literature

We report a case of myxoma with multiple recurrences in both the atrium and ventricle in a 26-year-old woman five years after the surgical removal of left atrial myxoma, Her 52-year-old mother had a similar medical history. To our knowledge, this was the first familial case who suffered multifocal cardiac myxoma recurrences without any sign of the myxoma complex. Based on our understanding of the mechanism of recurrence, the approaches to prevent the recurrence, and markers to predict recurrence, we propose that multifocal recurrences, as reported herein, may result from a combination of familial predisposition and multifocal onset. The hi-atrial surgical approach and transesophageal echocardiography are preferred for patients with recurrent cardiac myxomas, especially for those with multiple recurrences and familial myxoma. Immunological and genetic screenings may help to identify family members at risk for developing this disease.