Granzyme B as a novel factor involved in cardiovascular diseases

SummaryApoptosis plays an important role in cardiovascular diseases such as atherosclerosis, ischemic heart disease, and congestive heart failure. Previous studies have demonstrated that oxidative stress, physiological stress, and inflammatory cytokines such as tumor necrosis factor and Fas ligand are involved in apoptosis of cardiovascular system. We demonstrate that another apoptosis-related pathway, i.e. granzyme B/perforin system is involved in cardiovascular diseases. Expression of granzyme B, a member of serine protease family is increased in acute coronary syndrome, coronary artery disease with end-stage renal disease, and subacute stage of acute myocardial infarction. Although granzyme B is extensively researched in immunological disorders, the role of granzyme B/perforin system was not clear in the cardiovascular field. In addition, little is known regarding the inhibition of granzyme B system in the clinical situation. In this review we demonstrate recent findings of granzyme B in cardiovascular diseases and possible therapeutic applications of inhibiting the granzyme B/perforin system

4-Hydroxy-2-Nonenal-Modified Glyceraldehyde-3-Phosphate Dehydrogenase Is Degraded by Cathepsin G in Rat Neutrophils

Degradation of oxidized or oxidatively modified proteins is an essential part of the antioxidant defenses of cells. 4-Hydroxy-2-nonenal, a major reactive aldehyde formed by lipid peroxidation, causes many types of cellular damage. It has been reported that 4-hydroxy-2-nonenal-modified proteins are degraded by the ubiquitin-proteasome pathway or, in some cases, by the lysosomal pathway. However, our previous studies using U937 cells showed that 4-hydroxy-2-nonenal-modified glyceraldehyde-3-phosphate dehydrogenase is degraded by cathepsin G. In the present study, we isolated the 4-hydroxy-2-nonenal-modified glyceraldehyde-3-phosphate dehydrogenase-degrading enzyme from rat neutrophils to an active protein fraction of 28 kDa. Using the specific antibody, the 28 kDa protein was identified as cathepsin G. Moreover, the degradation activity was inhibited by cathepsin G inhibitors. These results suggest that cathepsin G plays a crucial role in the degradation of 4-hydroxy-2-nonenal-modified glyceraldehyde-3-phosphate dehydrogenase

Expression of vascular endothelial growth factor in patients with acute myocardial infarction

AbstractOBJECTIVEThe purpose of this study was to investigate the clinical significance of vascular endothelial growth factor (VEGF) in acute myocardial infarction (AMI). We also examined the involvement of peripheral blood mononuclear cells (PBMCs), which are a possible source of VEGF in AMI.BACKGROUNDVEGF is a potent endothelial cell–specific mitogen and could affect the outcome of AMI.METHODSThirty patients with AMI were used for this study. Serum and PBMCs were isolated from peripheral blood on days 1, 7, 14 and 21 after the onset of AMI. PBMCs were cultured at a density of 5 × 106cells/ml for 24 h. VEGF levels in serum and the culture media were measured by enzyme-linked immunosorbent assay using a specific anti-human VEGF antibody.RESULTSSerum VEGF levels elevated gradually after the onset of AMI and reached a peak on day 14. VEGF levels in the culture medium of PBMCs after incubation for 24 h (PBMC-VEGF) were maximally elevated 7 days after the onset. Maximum serum VEGF levels showed significant positive correlations with maximum creatine phosphokinase (CPK) levels (r = +0.70, p < 0.001), but maximum PBMC-VEGF levels did not correlate with maximum CPK levels. Patients showing improvement in left ventricular systolic function during the course of AMI showed significantly higher PBMC-VEGF levels than patients without improvement.CONCLUSIONSThe extent of myocardial damage contributes to the elevation of serum VEGF levels in AMI. VEGF produced by PBMCs may play an important role in the improvement of left ventricular function by promoting angiogenesis and reendothelialization after AMI

-4 Heart Asia Roles of ghrelin in left-ventricular remodelling after acute myocardial infarction

. Multivariate regression analysis showed that ghrelin on day 14 is a significant predictor of LV remodelling after AMI (b¼ +0.44, p¼0.001). Conclusion To our knowledge, this is the first report that shows a relation between circulating ghrelin after AMI and the progression of LV remodelling in the chronic phase. The elevation of ghrelin after AMI might be a compensatory mechanism to attenuate LV remodelling

Automatic Puncture Timing Detection for Multi-Camera Injection Motion Analysis

Precisely detecting puncture times has long posed a challenge in medical education. This challenge is attributable not only to the subjective nature of human evaluation but also to the insufficiency of effective detection techniques, resulting in many medical students lacking full proficiency in injection skills upon entering clinical practice. To address this issue, we propose a novel detection method that enables automatic detection of puncture times during injection without needing wearable devices. In this study, we utilized a hardware system and the YOLOv7 algorithm to detect critical features of injection motion, including puncture time and injection depth parameters. We constructed a sample of 126 medical injection training videos of medical students, and skilled observers were employed to determine accurate puncture times. Our experimental results demonstrated that the mean puncture time of medical students was 2.264 s and the mean identification error was 0.330 s. Moreover, we confirmed that there was no significant difference (p = 0.25 with a significance level of α = 0.05) between the predicted value of the system and the ground truth, which provides a basis for the validity and reliability of the system. These results show our system’s ability to automatically detect puncture times and provide a novel approach for training healthcare professionals. At the same time, it provides a key technology for the future development of injection skill assessment systems