Integrative Bioinformatics–Gene Network Approach Reveals Linkage between Estrogenic Endocrine Disruptors and Vascular Remodeling in Peripheral Arterial Disease

Abstract

Vascular diseases, including peripheral arterial disease (PAD), pulmonary arterial hypertension, and atherosclerosis, significantly impact global health due to their intricate relationship with vascular remodeling. This process, characterized by structural alterations in resistance vessels, is a hallmark of heightened vascular resistance seen in these disorders. The influence of environmental estrogenic endocrine disruptors (EEDs) on the vasculature suggests a potential exacerbation of these alterations. Our study employs an integrative approach, combining data mining with bioinformatics, to unravel the interactions between EEDs and vascular remodeling genes in the context of PAD. We explore the molecular dynamics by which EED exposure may alter vascular function in PAD patients. The investigation highlights the profound effect of EEDs on pivotal genes such as ID3, LY6E, FOS, PTP4A1, NAMPT, GADD45A, PDGF-BB, and NFKB, all of which play significant roles in PAD pathophysiology. The insights gained from our study enhance the understanding of genomic alterations induced by EEDs in vascular remodeling processes. Such knowledge is invaluable for developing strategies to prevent and manage vascular diseases, potentially mitigating the impact of harmful environmental pollutants like EEDs on conditions such as PAD.

Gene Interactions in Cerebral Cavernous Malformations: A Brief Report

“…This has provided valuable insight into the complex molecular and mechanistic processes involved in CCM. Previously, it has been demonstrated that ID3 has interactions with various vascular/blood vessel diseases [5][6][7][8][9][10][11][12][13][14][15]22,23] however; this new information can help to build the foundation for additional research within the focus of gene expression networks, bioinformatics, and data analytics. The small sample size in the GEO study for our analysis of DEGs might restrict statistical power, which increases the risk of type II errors and bias.…”

“…Inhibitor of DNA Binding/Differentiation -3 (ID3), which is part of a group of genes (ID1, ID2, ID3, and ID4), has been known to be expressed in endothelial cells and important for endothelial cell activation and embryonic vasculogesis [5][6][7][8]. While known as a transcriptional regulator that prevents stem cell differentiation, ID3 has been identified to show overlapping functions such as gene knockout dependent on cellular context and can be activated from external environmental exposure [8][9][10][11][12][13][14][15][16]. While ID3 has been associated with vascular malformations such as Hereditary Hemorrhagic Telangiectasia [6,7], little is known about the association between ID3 and cerebral cavernous malformation.…”

Molecular Biomarkers in Lymphangioleiomyomatosis (LAM)

“…Estrogen regulated gene transcription may modulate signaling to activate mTOR. Various studies have shown that estrogen and estrogen disruptors may promote various transcriptional regulators such as ID proteins to be involved in various molecular activities such as vascular remodeling, stem cell differentiation, and pulmonary dysfunction [3][4][5][6][7][8][9][10][11]. While genes such as TSC1 and TSC2 are known to be involved with LAM development [1][2][3][4][5], very little is known about other genes that are associated with the disorder.…”