Interrogating cardiac muscle cell mechanobiology on stiffness gradient hydrogels

Mechanobiology of H9C2 cells and neonatal cardiomyocytes mapped using stiffness gradient hydrogels with a range of extracellular matrix coatings, revealing stiffness-driven trends in cell morphology, YAP and MRTF-A expression.

Integrative Analyses of Genes Associated with Subcutaneous Insulin Resistance

: Insulin resistance is present in the majority of patients with non-insulin-dependent diabetes mellitus (NIDDM) and obesity. In this study, we aimed to investigate the key genes and potential molecular mechanism in insulin resistance. Expression profiles of the genes were extracted from the Gene Expression Omnibus (GEO) database. Pathway and Gene Ontology (GO) enrichment analyses were conducted at Enrichr. The protein–protein interaction (PPI) network was settled and analyzed using the Search Tool for the Retrieval of Interacting Genes (STRING) database constructed by Cytoscape software. Modules were extracted and identified by the PEWCC1 plugin. The microRNAs (miRNAs) and transcription factors (TFs) which control the expression of differentially expressed genes (DEGs) were analyzed using the NetworkAnalyst algorithm. A database (GSE73108) was downloaded from the GEO databases. Our results identified 873 DEGs (435 up-regulated and 438 down-regulated) genetically associated with insulin resistance. The pathways which were enriched were pathways in complement and coagulation cascades and complement activation for up-regulated DEGs, while biosynthesis of amino acids and the Notch signaling pathway were among the down-regulated DEGs. Showing GO enrichment were cardiac muscle cell–cardiac muscle cell adhesion and microvillus membrane for up-regulated DEGs and negative regulation of osteoblast differentiation and dendrites for down-regulated DEGs. Subsequently, myosin VB (MYO5B), discs, large homolog 2(DLG2), axin 2 (AXIN2), protein tyrosine kinase 7 (PTK7), Notch homolog 1 (NOTCH1), androgen receptor (AR), cyclin D1 (CCND1) and Rho family GTPase 3 (RND3) were diagnosed as the top hub genes in the up- and down-regulated PPI network and modules. In addition, GATA binding protein 6 (GATA6) , ectonucleotide pyrophosphatase/phosphodiesterase 5 (ENPP5), cyclin D1 (CCND1) and tubulin, beta 2A (TUBB2A) were diagnosed as the top hub genes in the up- and down-regulated target gene–miRNA network, while tubulin, beta 2A (TUBB2A), olfactomedin-like 1 (OLFML1), prostate adrogen-regulated mucin-like protein 1 (PARM1) and aldehyde dehydrogenase 4 family, member A1 (ALDH4A1)were diagnosed as the top hub genes in the up- and down-regulated target gene–TF network. The current study based on the GEO database provides a novel understanding regarding the mechanism of insulin resistance and may provide novel therapeutic targets.

The protective effect of AT1-antibody against myocardial ischemia-reperfusion injury through inhibition of inflammation and apoptosis

Myocardial ischemia and reperfusion (I/R) injury is known to occur on restoration of coronary flow after a period of myocardial ischemia. Angiotensin II (Ang II) is the most important bioactive substance of the renin-angioensin system (RAS), and exerts its physiological actions through AT1 receptors by regulating vascular tension and blood flow, and promoting cell growth and proliferation. The aim of the present study is to investigate the effects and its possible underlying mechanisms of AT1-AB on myocardial ischemia/reperfusion (I/R) injury. To test this hypothesis, we randomly assigned four groups (six mice per group) for experiment. To produce myocardial injury, the left anterior coronary artery (LAD) was occluded for 30 min, followed by 120 min of reperfusion in anesthetized mice. In the mice heart subjected to I/R injury, pretreatment AT1-AB (1mcg/gm) decreased the pathological scores of myocardium, and significantly attenuated I/R-induced increases of myocardial TNFα, IL-1β, IL-6. Further, 1mcg/gm AT1-AB significantly attenuated cTn-I and reduced apoptosis index of cardiac muscle cell of mice subjected to I/R injury. Therefore, these results demonstrate that AT1-AB exhibits significant protective effect against myocardial I/R injury which is related to inhibition of the release of inflammatory cytokines and the apoptosis of cardiac muscle cell.