Blood pressure (BP) is determined by several physiological factors that are regulated by a range ... more Blood pressure (BP) is determined by several physiological factors that are regulated by a range of complex neural, endocrine, and paracrine mechanisms. This study examined a collection of 198 human genes related to BP regulation, in the biological processes and functional prisms, as well as gene expression in organs and tissues. This was made in conjunction with an orthology analysis performed in 19 target organisms along the phylogenetic tree. We have demonstrated that transport and signaling, as well as homeostasis in general, are the most prevalent biological processes associated with BP gene orthologs across the examined species. We showed that these genes and their orthologs are expressed primarily in the kidney and adrenals of complex organisms (e.g., high order vertebrates) and in the nervous system of low complexity organisms (e.g., flies, nematodes). Furthermore, we have determined that basic functions such as ion transport are ancient and appear in all organisms, while mo...
It is well known that a myriad of medications and substances can induce side effects that are rel... more It is well known that a myriad of medications and substances can induce side effects that are related to blood pressure (BP) regulation. This study aims to investigate why certain drugs tend to cause iatrogenic hypertension (HTN) and focus on drug targets that are implicated in these conditions.Databases and resources such as SIDER, DrugBank, and Genomatix were utilized in order to bioinformatically investigate HTN-associated drug target-genes for which HTN is a side effect. A tree-like map was created, representing interactions between 198 human genes that relate to the blood pressure system. 72 HTN indicated drugs and 160 HTN-inducing drugs were investigated. HTN-associated genes affected by these drugs were identified. HTN indicated drugs, which target nearly all branches of the interaction tree, were shown to exert an effect on most functional sub-systems of the BP regulatory system; and specifically, for the adrenergic and dopaminergic receptor pathways. High prevalence (25 genes) of shared targets between the HTN indicated and HTN-inducing drug categories was demonstrated. We focus on six drug families which are not indicated for HTN treatment, yet are reported as a major cause for blood pressure side effects. We show the molecular mechanisms that may lead to this iatrogenic effect. Such an analysis may have clinical implications that could allow for the development of tailored medicine with fewer side effects.
The goal of this study was to investigate genes associated with essential hypertension from a sys... more The goal of this study was to investigate genes associated with essential hypertension from a system perspective, making use of bioinformatic tools to gain insights that are not evident when focusing at a detail-based resolution. Using various databases (pathways, Genome Wide Association Studies, knockouts etc.), we compiled a set of about 200 genes that play a major role in hypertension and identified the interactions between them. This enabled us to create a protein-protein interaction network graph, from which we identified key elements, based on graph centrality analysis. Enriched gene regulatory elements (transcription factors and microRNAs) were extracted by motif finding techniques and knowledge-based tools. We found that the network is composed of modules associated with functions such as water retention, endothelial vasoconstriction, sympathetic activity and others. We identified the transcription factor SP1 and the two microRNAs miR27 (a and b) and miR548c-3p that seem to ...
Blood pressure (BP) is determined by several physiological factors that are regulated by a range ... more Blood pressure (BP) is determined by several physiological factors that are regulated by a range of complex neural, endocrine, and paracrine mechanisms. This study examined a collection of 198 human genes related to BP regulation, in the biological processes and functional prisms, as well as gene expression in organs and tissues. This was made in conjunction with an orthology analysis performed in 19 target organisms along the phylogenetic tree. We have demonstrated that transport and signaling, as well as homeostasis in general, are the most prevalent biological processes associated with BP gene orthologs across the examined species. We showed that these genes and their orthologs are expressed primarily in the kidney and adrenals of complex organisms (e.g., high order vertebrates) and in the nervous system of low complexity organisms (e.g., flies, nematodes). Furthermore, we have determined that basic functions such as ion transport are ancient and appear in all organisms, while mo...
It is well known that a myriad of medications and substances can induce side effects that are rel... more It is well known that a myriad of medications and substances can induce side effects that are related to blood pressure (BP) regulation. This study aims to investigate why certain drugs tend to cause iatrogenic hypertension (HTN) and focus on drug targets that are implicated in these conditions.Databases and resources such as SIDER, DrugBank, and Genomatix were utilized in order to bioinformatically investigate HTN-associated drug target-genes for which HTN is a side effect. A tree-like map was created, representing interactions between 198 human genes that relate to the blood pressure system. 72 HTN indicated drugs and 160 HTN-inducing drugs were investigated. HTN-associated genes affected by these drugs were identified. HTN indicated drugs, which target nearly all branches of the interaction tree, were shown to exert an effect on most functional sub-systems of the BP regulatory system; and specifically, for the adrenergic and dopaminergic receptor pathways. High prevalence (25 genes) of shared targets between the HTN indicated and HTN-inducing drug categories was demonstrated. We focus on six drug families which are not indicated for HTN treatment, yet are reported as a major cause for blood pressure side effects. We show the molecular mechanisms that may lead to this iatrogenic effect. Such an analysis may have clinical implications that could allow for the development of tailored medicine with fewer side effects.
The goal of this study was to investigate genes associated with essential hypertension from a sys... more The goal of this study was to investigate genes associated with essential hypertension from a system perspective, making use of bioinformatic tools to gain insights that are not evident when focusing at a detail-based resolution. Using various databases (pathways, Genome Wide Association Studies, knockouts etc.), we compiled a set of about 200 genes that play a major role in hypertension and identified the interactions between them. This enabled us to create a protein-protein interaction network graph, from which we identified key elements, based on graph centrality analysis. Enriched gene regulatory elements (transcription factors and microRNAs) were extracted by motif finding techniques and knowledge-based tools. We found that the network is composed of modules associated with functions such as water retention, endothelial vasoconstriction, sympathetic activity and others. We identified the transcription factor SP1 and the two microRNAs miR27 (a and b) and miR548c-3p that seem to ...
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Papers by Alon Botzer