Significant Heart Dysfunction Research Articles

Myocardial infarction protective effect of xyloglucan on Drosophila melanogaster: A review

Myocardial infarction, more often known as cardiac arrest, occurs when the supply of blood to the heart’s coronary artery decreases or ceases, causing damage to the heart muscle. Xyloglucan is a plant polysaccharide. Xyloglucan has been proven in several studies utilizing model organisms to reduce the risk of coronary heart disease by avoiding post-occlusion phases inhibiting apoptosis and enhancing energy metabolism. Many studies utilize Drosophila melanogaster because its SRY-related HMG-box 5 (SOX5) gene encodes a SOX family transcription factor; the human SOX5 ortholog, Sox102F, is well conserved in Drosophila melanogaster. Suppressing Sox102F in flies resulted in significant heart dysfunction, structural defects, and a disturbance in notch signal transduction. This demonstrates that SOX5 serves an important functional part in the heart and that variations in SOX5 concentrations may contribute to the possibility of myocardial infarction. Xyloglucan activity is significant in myocardial infarction and may be lowered in the myocardium after H/R damage by stimulating Notch signaling, which may benefit myocardial survival, angiogenesis, and cardiac function. This review discusses the roles of the human SOX5 and Drosophila SOX102F genes, the notch signaling system, and how xyloglucan in tamarind seeds may defend against heart damage by preventing apoptosis along with improving energy metabolism.

Abstract 16683: Profiling Cardiac Inflammation and Molecular Changes During the Transition of Hypertrophic to Dilated Cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) is a disease caused primarily by sarcomere gene mutations [like myosin-binding protein C3 ( MYBPC3 )], with several distinct phenotypes. Tissue-level inflammation has been reported in human HCM, tissue-specific neutrophil subsets, and their dysregulation cause inflammatory myopathies, and neutrophil extracellular traps (NETs) are associated with cardiac fibrosis in aged rodents. However, the mechanism(s) responsible for the broad phenotypic variability and changes observed over time transitioning from HCM to dilated cardiomyopathy (DCM) has not yet been elucidated. Objective: To determine the cardiac inflammatory signature of HCM and transition from HCM to DCM and its relationship to fibrosis and ventricular remodeling in an established MYBPC3 ( cMyBP-C t/t ) mouse model. Method and Results: Mixed-gender cMyBP-C +/+ (WT) and mutant mice ( cMyBP-C t/t ) underwent echocardiography and were euthanized at one, two and three months of age (n=8) and blood and hearts were harvested. Echocardiography and histopathology examination confirmed significant heart dysfunction and tissue remodeling in cMyBP-C t/t mice showing cardiac hypertrophy at one month of age (Left ventricular (LV) posterior wall systole 1.20 ±0.39 vs 1.51±0.49 and LV posterior wall diastole 0.96 ±0.22 vs 1.38 ±0.36 mm; * p<0.05 ), and DCM phenotype (LV internal diameter systole 2.40 ±0.41 vs 3.67 ±0.25 and LV internal diameter diastole 3.44 ±0.29 vs 4.30 ±0.39 mm; * p<0.05 ) along with myofibrillar loss and increased cardiac fibrosis at three months. Interestingly, LV dysfunction and hypertrophy resulted in a time-dependent increase in the activation of coagulation, as measured by plasma microvesicle tissue factor activity, thrombin antithrombin, and D-dimer. In silico analysis of RNA-Seq data from 3-months old cMyBP-C t/t mice heart revealed key genes and pathways associated with HCM, DCM, tissue remodeling, renin-angiotensin-aldosterone signaling, fibrosis, apoptosis, NETosis, and inflammation. Conclusions: The transition from HCM to a DCM phenotype involves proinflammatory and profibrotic signaling. Therapies directed at tissue-specific inflammation and NETs may be a novel and impactful strategy for HCM.