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

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.

Effect of Transcriptional Regulator ID3 on Pulmonary Arterial Hypertension and Hereditary Hemorrhagic Telangiectasia.

Pulmonary arterial hypertension (PAH) can be discovered in patients who have a loss of function mutation of activin A receptor-like type 1 (ACVRL1) gene, a bone morphogenetic protein (BMP) type 1 receptor. Additionally, ACVRL1 mutations can lead to hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, an autosomal dominant inherited disease that results in mucocutaneous telangiectasia and arteriovenous malformations (AVMs). Transcriptional regulator Inhibitor of DNA-Binding/Differentiation-3 (ID3) has been demonstrated to be involved in both PAH and HTT; however, the role of its overlapping molecular mechanistic effects has yet to be seen. This review will focus on the existing understanding of how ID3 may contribute to molecular involvement and perturbations thus altering both PAH and HHT outcomes. Improved understanding of how ID3 mediates these pathways will likely provide knowledge in the inhibition and regulation of these diseases through targeted therapies.

Inhibitor of DNA-Binding/Differentiation Proteins and Environmental Toxicants: Genomic Impact on the Onset of Depressive Dysfunction.

The ongoing growth of the international occurrence of depression and its ability to co-occur with other serious medical disorders, such as heart disease, cancer, diabetes, and Parkinson's disease, is a current public health problem. Inhibitor of DNA-Binding/Differentiation (ID) proteins are part of a group of transcriptional factors that have shown involvement in neurocognitive disorders and, therefore, may have influence on depressive disorders. Previously, it has been established that exposure to environmental estrogenic endocrine disruptors (EEDs), such as polychlorinated biphenyls (PCBs) and bisphenol A (BPA), have played an important role in the modulation of depressive disorders. Hence, based on many studies, we consider the impact of these environmental pollutants on the group of ID proteins and how they impact depressive outcomes. Improved knowledge of how ID proteins interact with depressive disorders, through EED exposure, will contribute essential evidence that can further benefit our public health community with innovative knowledge to prevent these types of mental illnesses.

Contribution of Inhibitor of Differentiation and Estrogenic Endocrine Disruptors to Neurocognitive Disorders.

The devastating growth in the worldwide frequency of neurocognitive disorders and its allied difficulties, such as decline in memory, spatial competency, and ability to focus, poses a significant psychological public health problem. Inhibitor of differentiation (ID) proteins are members of a family of helix-loop-helix (HLH) transcription factors. ID proteins have been demonstrated to be involved in neurodevelopmental and depressive diseases and, thus, may influence neurocognitive deficiencies due to environmental exposure. Previously, it has been demonstrated that environmental factors, such as estrogenic endocrine disruptors (EEDs), have played an essential role in the influence of various neurocognitive disorders such as Alzheimer's, dementia, and Parkinson's disease. Based on this increasing number of reports, we consider the impact of these environmental pollutants on ID proteins. Better understanding of how these ID proteins by which EED exposure can affect neurocognitive disorders in populations will prospectively deliver valuable information in the impediment and regulation of these diseases linked with environmental factor exposure.

Inhibitor of Differentiation-3 and Estrogenic Endocrine Disruptors: Implications for Susceptibility to Obesity and Metabolic Disorders.

The rising global incidence of obesity cannot be fully explained within the context of traditional risk factors such as an unhealthy diet, physical inactivity, aging, or genetics. Adipose tissue is an endocrine as well as a metabolic organ that may be susceptible to disruption by environmental estrogenic chemicals. Since some of the endocrine disruptors are lipophilic chemicals with long half-lives, they tend to bioaccumulate in the adipose tissue of exposed populations. Elevated exposure to these chemicals may predispose susceptible individuals to weight gain by increasing the number and size of fat cells. Genetic studies have demonstrated that the transcriptional regulator inhibitor of differentiation-3 (ID3) promotes high fat diet-induced obesity in vivo. We have shown previously that PCB153 and natural estrogen 17ß-estradiol increase ID3 expression. Based on our findings, we postulate that ID3 is a molecular target of estrogenic endocrine disruptors (EEDs) in the adipose tissue and a better understanding of this relationship may help to explain how EEDs can lead to the transcriptional programming of deviant fat cells. This review will discuss the current understanding of ID3 in excess fat accumulation and the potential for EEDs to influence susceptibility to obesity or metabolic disorders via ID3 signaling.

Contribution of Inhibitor of DNA Binding/Differentiation-3 and Endocrine Disrupting Chemicals to Pathophysiological Aspects of Chronic Disease.

The overwhelming increase in the global incidence of obesity and its associated complications such as insulin resistance, atherosclerosis, pulmonary disease, and degenerative disorders including dementia constitutes a serious public health problem. The Inhibitor of DNA Binding/Differentiation-3 (ID3), a member of the ID family of transcriptional regulators, has been shown to play a role in adipogenesis and therefore ID3 may influence obesity and metabolic health in response to environmental factors. This review will highlight the current understanding of how ID3 may contribute to complex chronic diseases via metabolic perturbations. Based on the increasing number of reports that suggest chronic exposure to and accumulation of endocrine disrupting chemicals (EDCs) within the human body are associated with metabolic disorders, we will also consider the impact of these chemicals on ID3. Improved understanding of the ID3 pathways by which exposure to EDCs can potentiate complex chronic diseases in populations with metabolic disorders (obesity, metabolic syndrome, and glucose intolerance) will likely provide useful knowledge in the prevention and control of complex chronic diseases associated with exposure to environmental pollutants.