Heart failure (HF) is the end-stage of various diseases, especially ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM). We aimed to investigate the common molecular mechanism of ICM and DCM. Differentially expressed genes (DEGs) of ICM or DCM samples compared with control were identified in GSE1869, GSE5406, GSE57338, GSE79962, GSE116250, and GSE46224 datasets. Functional enrichment analysis and protein–protein network analysis of the coregulated DEGs in at least four datasets were performed using the online tools of DAVID, the Metascape database, and the STRING database. Hub genes of HF were identified and validated by western blotting (WB) and immunohistochemistry in our tissue microarray (TMA). Seventy-four coregulated ICM and 126 coregulated DCM relevant DEGs were identified. Moreover, 59 common genes between ICM and DCM relevant DEGs were obtained, which were mainly involved in cardiac fibrosis and several signal pathways, such as Wnt signal pathway, PI3K-Akt signal pathway, and HIF-1A signal pathway. Among the six hub genes with top degrees, asporin (ASPN) had a relatively higher correlation with LVEF. Finally, TMA and WB results revealed that the ASPN protein was significantly increased in ICM and DCM left ventricular samples. The present study revealed some common molecular mechanisms of HF with different causes. Furthermore, ASPN may be a potential promising biomarker for HF.

Background: Foam cells (FCs) play crucial roles in the process of all stages of atherosclerosis. Smooth muscle cells (SMCs) and macrophages are the major sources of FCs. This study aimed to identify the common molecular mechanism in these two types of FCs. Methods: GSE28829, GSE43292, GSE68021, and GSE54666 were included to identify the differentially expressed genes (DEGs) associated with FCs derived from SMCs and macrophages. Gene Ontology biological process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by using the DAVID database. The co-regulated genes associated with the two origins of FCs were validated (GSE9874), and their expression in vulnerable atherosclerosis plaques (GSE120521 and GSE41571) was assessed. Results: A total of 432 genes associated with FCs derived from SMCs (SMC-FCs) and 81 genes associated with FCs derived from macrophages (M-FCs) were identified, and they were mainly involved in lipid metabolism, inflammation, cell cycle/apoptosis. Furthermore, three co-regulated genes associated with FCs were identified: GLRX, RNF13, and ABCA1. These three common genes showed an increased tendency in unstable or ruptured plaques, although in some cases, no statistically significant difference was found. Conclusions: DEGs related to FCs derived from SMCs and macrophages have contributed to the understanding of the molecular mechanism underlying the formation of FCs and atherosclerosis. GLRX, RNF13, and ABCA1 might be potential targets for atherosclerosis treatment.

Background: Practical biosignatures and thorough understanding of regulatory processes of hypertrophic obstructive cardiomyopathy (HOCM) are still lacking.Methods: Firstly, public data from GSE36961 and GSE89714 datasets of Gene Expression Omnibus (GEO), Gene database of NCBI (National Center of Biotechnology Information) and Online Mendelian Inheritance in Man (OMIM) database were merged into a candidate gene set of HOCM. Secondly, weighted gene co-expression network analysis (WGCNA) for the candidate gene set was carried out to determine premier co-expressed genes. Thirdly, significant regulators were found out by virtue of a multi-factor regulatory network of long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), microRNAs (miRNAs) and transcription factors (TFs) with molecule interreactions from starBase v2.0 database and TRRUST v2 database. Ultimately, HOCM unsupervised clustering and “tsne” dimensionality reduction was employed to gain hub genes, whose classification performance was evaluated by a multinomial model of lasso logistic regression analysis binded with receiver operating characteristic (ROC) curve.Results: Two HOCM remarkably-interrelated modules were from WGCNA, followed by the recognition of 32 crucial co-expressed genes. The multi-factor regulatory network disclosed 7 primary regulatory agents, containing lncRNAs (XIST, MALAT1, and H19), TFs (SPI1 and SP1) and miRNAs (hsa-miR-29b-39 and has-miR-29a-3p). Four clusters of HOCM and 4 hub genes (COMP, FMOD, AEBP1 and SULF1) significantly expressing in preceding four subtypes were obtained, while ROC curve demonstrated satisfactory performance of clustering and 4 genes.Conclusions: Our consequences furnish valuable resource which may bring about prospective mechanistic and therapeutic anatomization in HOCM.

Functional small-diameter tissue-engineered blood vessels (TEBVs) have been developed in silico using biodegradable polymeric scaffolds under pulsatile perfusion. Accurate simulation of physiological mechanical stimulations in vitro is a crucial factor in vascular engineering. However, little is known about the patterns of mechanical stimulation on silicone tubes. This study aimed to determine the optimal mechanical conditions required for inducing circumferential deformations in silicone tubes during in vitro vascular development under pulsatile perfusion. For this purpose, we established a data acquisition (DAQ) system with a laser micrometer and pressure transducers to evaluate changes in the diameter of silicone tubes in response to pulsatile flow and validated the results on cultured TEBVs. The established DAQ system showed satisfactory reproducibility for measuring diameter variation in the in silico model. Furthermore, the hardness and thickness of the silicone tubes affected the mechanical conditioning in the three-dimensional culture system under different working pressures, frequencies, and circumferential deformations. We demonstrated a simple and reliable approach to quantify the circumferential strain and deformations to ensure optimal mechanical stimulation of the cultured TEBVs under pulsatile perfusion. Based on the results, we were able to dynamically culture dense cellularized small-diameter TEBVs. This study highlights the importance of mechanical stimulation in vascular tissue engineering. Impact statement: This study demonstrated a direct and noncontact data acquisition system for quantifying the strain on the supporting silicone medium during three-dimensional tissue-engineered blood vessel culture, which can help optimize the mechanical parameters for vascular tissue engineering.

Objective: Hypertrophic obstructive cardiomyopathy (HOCM) is one of the main reasons for sudden cardiac death (SCD) of young people. Researches have revealed that immune-related genes are closely relevant with HOCM. Therefore, it is important to explore the key immune regulatory mechanisms and biomarkers of HOCM.Methods: We used many bioinformatics methods, including linear models for microarray analysis (LIMMA), protein-protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes pathway (KEGG), and CIBERSORT to assess the key pathway and hub genes involved in HOCM. Furthermore, expression levels of hub genes were validated in human tissue.Results: Our results showed that the degree of infiltration of five immune cells were linked to HOCM, including monocytes, macrophages M2, NK cell resting, B cells native, and T cells regulatory (Tregs). A total of 7 hub genes (CCL2, CXCL8, FOS, MAP2K1, NFKBIA, STAT3, and TNFRSF1A) were identified and validated by qt-PCR. The core genes including CCL2, MAP2K1, NFKBIA, STAT3, and TNFRSF1A are closely related to monocytes infiltration in HOCM.Conclusion: Taken together, our research will provide useful information to explore the immune mechanisms underlying HOCM and the potential targets for therapy. The candidate genes CCL2, MAP2K1, NFKBIA, STAT3, and TNFRSF1A were involved in the regulation of monocytes tissue infiltration, which is closely related to the HOCM.