There is emerging data indicating that long-standing vigorous exercise may be associated with atrial structural remodelling. This remodelling process is may be the cause of the increasing frequency ...of atrial arrythmias in athletes. Early diagnosis of atrial remodelling by atrial imaging could have a role in management of atrial arrythmias in elite athletes. In this study we aimed to diagnose early phases of atrial remodelling in elite athletes. Two groups of athletes including professional weight lifters (n = 33), professional marathoners (n = 32) and sedentary participants (n = 30) were enrolled. We also studied patients who received cardiotoxic chemotherapy (n = 10) for comparison. Serum TGF-beta level as a marker of fibrosis was measured. Both left atrial (LA) 3D volume and strain values were analysed. There was a positive correlation between serum TGF-beta levels and LA volumes and negative correlation between TGF-beta levels and strain values. TGF-beta levels were higher among chemotherapy and weight lifter groups, compared to control and marathoner groups mean 0.57 ± 0.3 and 0.55 ± 0.2 vs. 0.45 ± 0.2 and 0.47 ± 0.2, respectively, p = 0.005. LA volumes were higher among chemotherapy and weight lifter groups median 33 (26–38) and 31 (23–36) respectively, p = 0.005, and strain values were lower in these two groups mean 20.3 ± 2.5 and 24.6 ± 4.5, respectively, p < 0.005 compared to control and marathoner groups. Total exercise volume was higher in weight lifter group compared to marathoners 13,780 (2496–36,400) vs. 4732 (780–44928), respectively, p = 0.001. There wasn’t any difference between any group regarding left ventricular systolic and diastolic functions. Vigorous exercise causes atrial remodelling and fibrosis in elite athletes. Strength exercise carries higher risk for atrial fibrosis than endurance exercise. Burden of exercise is correlated with the severity of cardiac fibrosis. Echocardiographic evaluation of the left atrium and TGF-beta levels may help to detect subclinical cardiac remodelling and fibrosis.
Familial hemophagocytic lymphohistiocytosis 2 (FHL2) is the most common familial type of hemophagocytic lymphohistiocytosis with immune dysregulation. FHL2 patients have mutations in the perforin ...gene which cause overactivation and proliferation of cytotoxic T lymphocytes and natural killer cells. Perforin is the key component of the cytolytic granule response function of cytotoxic T lymphocytes and natural killer cells. Perforin dysfunction causes a cytotoxic immune deficiency with a clinical outcome of uncontrolled and continuous immune stimulation response. This excessive stimulation leads to continuous systemic inflammation and, ultimately, multiorgan failure. Radical therapy is hematopoietic stem cell transplantation which is limited by the availability of a donor. Exacerbations of inflammatory attacks require a palliative immunosuppressive regimen. There is a need for an alternative or adjuvant therapy to maintain these patients when immunosuppression is ineffective or a donor is not available. Beneficial actions of mesenchymal stem cells (MSCs) have been shown in autoimmune diseases in clinical trials and are attributed to their immune-modulatory properties. This study aimed to assess the immune-modulatory effect of MSCs in an in-vitro model of FHL2.
We generated a targeted mutation in the perforin gene of NK92 cells to create an in-vitro FLH2 model using Crispr/Cas technology. A coculture setup was employed to assess the immunomodulatory efficacy of MSCs.
Engineered NK92 clones did not show PRF1 mRNA expression and failed to secrete perforin upon phorbol myristate acetate-ionomycin stimulation, providing evidence for a valid FHL2 model. Coculture media of the engineered cells were investigated for the abundance of several cytokines. Coculture with MSCs revealed a reduction in major proinflammatory cytokines and an induction in anti-inflammatory and immunomodulatory cytokines compared to the parental NK92 cells.
This study shows the ameliorating effect of MSCs as an adjuvant immune modulator toward the therapy of FHL2 patients. MSCs are supportive therapy candidates for FHL2 patients under circumstances where prolonged immunosuppression is required to gain time before allogeneic hematopoietic stem cell transplantation.
PDF