Global Expression Profiling Identifies a Novel Hyaluronan Synthases 2 Gene in the Pathogenesis of Lower Extremity Varicose Veins

Abstract

Lower extremities varicose veins (VV) are among the most easily recognized venous abnormalities. The genetic mechanism of VV is largely unknown. In this study, we sought to explore the global expressional change of VV and identify novel genes that might play a role in VV. We used next-generation ribonucleic acid (RNA) sequence (RNA seq) technology to study the global messenger RNA expressional change in the venous samples of five diseased and five control patients. We identified several differentially expressed genes, which were further confirmed by conventional reverse transcription polymerase chain reaction (RT-PCR). Using these significant genes we performed in silico pathway analyses and found distinct transcriptional networks, such as angiogenesis, cell adhesion, vascular injury, and carbohydrate metabolisms that might be involved in the mechanism of VV. Among these significant genes, we also found hyaluronan synthases 2 gene (HAS2) played a pivotal role and governed all these pathways. We further confirmed that HAS2 expression was decreased in the venous samples of patients with VV. Finally, we used a zebrafish model with fluorescence emitting vasculature and red blood cells to see the morphological changes of the venous system and blood flow. We found that HAS2 knockdown in zebrafish resulted in dilated venous structural with static venous flow. HAS2 may modulate the transcriptional networks of angiogenesis, cell adhesion, vascular injury, and carbohydrate metabolisms in venous tissues and downregulation of HAS2 may underlie the mechanism of VV.

Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease

“…Some studies indicated altered expression of genes in veins obtained from patients with CVD and venous ulcers [57][58][59][60] but none of the genes indicated in abovementioned research were found in our study. These differences could be related to the biological material type, inclusion criteria and methodological approach.…”

Real-world evidence and optimization of vocal dysfunction in end-stage renal disease patients with secondary hyperparathyroidism

“…For Part I of this study, we compared the comorbidities and demographic characteristics of the study and comparison cohorts; here, we used Pearson’s chi-square test and an unpaired Student t test to compare categorical and continuous variables, respectively 31 . Next, we included control variables such as sex, age, income level, urbanization level, and comorbidities as covariates in our univariate model to perform a univariate analysis 32 . The variables with p < 0.1 in the univariate analysis were included in the multivariate analysis.…”

Dissecting the role of hyaluronan synthases in the tumor microenvironment

“…Notably, some of the cardiac defects can be rescued in explants from Has2 À/À mice by exogenous HA [65,66]. Interestingly, knockdown of Has2 in zebrafish leads to abnormal blood vessels with static venous flow, suggesting that HAS2 might be involved in the pathogenesis of venous disease as well [67].…”