Human umbilical cord mesenchymal stem cells inhibit coronary artery injury in mice with Lactobacillus casei wall extract-induced kawasaki disease

Kawasaki disease (KD) is a serious threat to children’s physical and mental health. This study investigated the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on KD coronary arteritis induced by Lactobacillus casei wall extract (LCWE) in an animal model. Sixty BALB/C mice were randomly assigned to three groups (n = 20 mice per group). Mice in the model and stem-cell groups were injected with LCWE, while the control-group mice were injected with phosphate-buffered saline (PBS) for 2 days. At day 16 of modeling, PBS was injected into the control and model-group mice, and hUC-MSCs were injected into the stem-cell group mice for 10 days. At days 4, 15, 26, and 32 of modeling, echocardiography and histopathology were performed to examine the cardiac structure and the morphological changes in the coronary arteries in each group. B-ultrasonography showed that 57.5% (23/40) of the mice had coronary artery lesions, of which 5% (2/40) had right coronary artery aneurysm, 27.5% (11/40) had coronary artery wall thickening, a widened inner diameter of the main artery of the left coronary artery, and thickened intima. Histopathology showed slight swelling of the epicardium of the aortic valve, mitral valve, right ventricle, and atrium, as well as scattered infiltration of a few neutrophils. Following hUC-MSCs intervention treatment, B-ultrasonography showed a decrease in the main coronary artery diameter, while histopathology showed no obvious vascular inflammatory reaction or other obvious abnormalities. These findings highlight that hUC-MSCs inhibit coronary artery injury in animal models of KD induced by LCWE

TRPV1 Activation Attenuates High-Salt Diet-Induced Cardiac Hypertrophy and Fibrosis through PPAR- δ

High-salt diet-induced cardiac hypertrophy and fibrosis are associated with increased reactive oxygen species production. Transient receptor potential vanilloid type 1 (TRPV1), a specific receptor for capsaicin, exerts a protective role in cardiac remodeling that resulted from myocardial infarction, and peroxisome proliferation-activated receptors δ (PPAR-δ) play an important role in metabolic myocardium remodeling. However, it remains unknown whether activation of TRPV1 could alleviate cardiac hypertrophy and fibrosis and the effect of cross-talk between TRPV1 and PPAR-δ on suppressing high-salt diet-generated oxidative stress. In this study, high-salt diet-induced cardiac hypertrophy and fibrosis are characterized by significant enhancement of HW/BW%, LVEDD, and LVESD, decreased FS and EF, and increased collagen deposition. These alterations were associated with downregulation of PPAR-δ, UCP2 expression, upregulation of iNOS production, and increased oxidative/nitrotyrosine stress. These adverse effects of long-term high-salt diet were attenuated by chronic treatment with capsaicin. However, this effect of capsaicin was absent in TRPV1−/− mice on a high-salt diet. Our finding suggests that chronic dietary capsaicin consumption attenuates long-term high-salt diet-induced cardiac hypertrophy and fibrosis. This benefit effect is likely to be caused by TRPV1 mediated upregulation of PPAR-δ expression

A novel noninvasive method to detect rejection after heart transplantation

Prompt and accurate detection of rejection prior to pathological changes after organ transplantation is vital for monitoring rejections. Although biopsy remains the current gold standard for rejection diagnosis, it is an invasive method and cannot be repeated daily. Thus, noninvasive monitoring methods are needed. In this study, by introducing an IL-2 neutralizing monoclonal antibody (IL-2 N-mAb) and immunosuppressants into the culture with the presence of specific stimulators and activated lymphocytes, an activated lymphocyte-specific assay (ALSA) system was established to detect the specific activated lymphocytes. This assay demonstrated that the suppression in the ALSA test was closely related to the existence of specific activated lymphocytes. The ALSA test was applied to 47 heart graft recipients and the proliferation of activated lymphocytes from all rejection recipients proven by endomyocardial biopsies was found to be inhibited by spleen cells from the corresponding donors, suggesting that this suppression could reflect the existence of activated lymphocytes against donor antigens, and thus the rejection of a heart graft. The sensitivity of the ALSA test in these 47 heart graft recipients was 100%; however, the specificity was only 37.5%. It was also demonstrated that IL-2 N-mAb was indispensible, and the proper culture time courses and concentrations of stimulators were essential for the ALSA test. This preliminary study with 47 grafts revealed that the ALSA test was a promising noninvasive tool, which could be used in vitro to assist with the diagnosis of rejection post-heart transplantation

Establishment of a mode casei wall extract in mice with effect of human umbilical cord mesenchymal stem cells coronary artery injury and pathological and ultrasound changes

Objective: To investigate the establishment of a model of Kawasaki disease mouse coronary artery injury caused by Lactobacillus Casei Wall Extract (LCWE) and the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on coronary artery injury and pathological and ultrasound changes. Methods: Sixty BALB/c mice were randomly assigned to 3 groups, each with 20 mice. The control group was given phosphate-buffered saline (PBS) intraperitoneally for 2 consecutive days; the model group and the stem cell group were immunized with the prepared LCWE for 2 consecutive days. From the 16th day of the immunological model, the control group and model group were injected with 300 μL PBS daily; the stem cell group was injected with 300 μL (105/mL) of human umbilical cord mesenchymal stem cells daily for 10 consecutive days.  The mice were killed in batches on the 4th, 15th, 26th, and 32nd day of immunization, and the morphological changes of the coronary arteries of the mice were observed by echocardiography and histopathology.  Results: LCWE can induce coronary artery damage similar to Kawasaki disease in mice. B-ultrasound showed that 57.5% (23/40) mice had coronary artery disease, of which 5% (2/40) had a right coronary artery aneurysm and 27.5% (11/40). Thickening of the coronary artery wall, widening of the inner diameter of the left coronary artery trunk, and thickening of the intima; histopathology showed mild swelling of the epicardium of the aortic valve, mitral valve, right ventricle and atrium, and a few neutral granulocytes were scattered and infiltrated, the coronary artery lumen within it was dilated and a small amount of myocardial cells died and collapsed, and the local fibrous connective tissue was significantly proliferated and accompanied by solid calcium salt deposition. After hUC-MSCs intervention treatment, the ultrasound showed that the inner diameter of the main coronary artery was reduced. Histopathology showed that there was a large amount of lymphocytes, eosinophils, and monocytes in the outer membrane of the left atrial appendage of the mouse. There was no obvious vasculitis and other infiltrations; obviously abnormal.  Conclusion: 1. Lactobacillus Casei Wall Extract (LCWE) can induce coronary arteritis in an animal model of Kawasaki Disease (KD).  2. Human umbilical cord mesenchymal stem cells have a therapeutic effect on coronary artery disease in animal models of Kawasaki disease

A novel noninvasive method to detect rejection after heart transplantation

Prompt and accurate detection of rejection prior to pathological changes after organ transplantation is vital for monitoring rejections. Although biopsy remains the current gold standard for rejection diagnosis, it is an invasive method and cannot be repeated daily. Thus, noninvasive monitoring methods are needed. In this study, by introducing an IL-2 neutralizing monoclonal antibody (IL-2 N-mAb) and immunosuppressants into the culture with the presence of specific stimulators and activated lymphocytes, an activated lymphocyte-specific assay (ALSA) system was established to detect the specific activated lymphocytes. This assay demonstrated that the suppression in the ALSA test was closely related to the existence of specific activated lymphocytes. The ALSA test was applied to 47 heart graft recipients and the proliferation of activated lymphocytes from all rejection recipients proven by endomyocardial biopsies was found to be inhibited by spleen cells from the corresponding donors, suggesting that this suppression could reflect the existence of activated lymphocytes against donor antigens, and thus the rejection of a heart graft. The sensitivity of the ALSA test in these 47 heart graft recipients was 100%; however, the specificity was only 37.5%. It was also demonstrated that IL-2 N-mAb was indispensible, and the proper culture time courses and concentrations of stimulators were essential for the ALSA test. This preliminary study with 47 grafts revealed that the ALSA test was a promising noninvasive tool, which could be used in vitro to assist with the diagnosis of rejection post-heart transplantation