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Review
. 2017 May;19(5):530-533.
doi: 10.1111/jch.12978. Epub 2017 Feb 21.

The concept of crosstalk-directed embryological target mining and its application to essential hypertension treatment failures

Alan Alper Sag  1 , Oguzhan Sal  2 , Yagmur Kilic  2 , Emine Meltem Onal  2 , Mehmet Kanbay  3
Affiliations
Review

The concept of crosstalk-directed embryological target mining and its application to essential hypertension treatment failures

Alan Alper Sag et al. J Clin Hypertens (Greenwich). 2017 May.

Abstract

This review aims to introduce the novel concept of embryological target mining applied to interorgan crosstalk network genesis, and applies embryological target mining to multidrug-resistant essential hypertension (a prototype, complex, undertreated, multiorgan systemic syndrome) to uncover new treatment targets and critique why existing strategies fail. Briefly, interorgan crosstalk pathways represent the next frontier for target mining in molecular medicine. This is because stereotyped stepwise organogenesis presents a unique opportunity to infer interorgan crosstalk pathways that may be crucial to discovering novel treatment targets. Insights gained from this review will be applied to patient management in a clinician-directed fashion.

Keywords: denervation; hypertension resistant to conventional therapy; hypertension, essential; radiology, interventional.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Crosstalk‐direct embryological target mining (CTD‐ETM) analysis in the development of hypertension by the retinoic acid crosstalk zone and dopaminergic tone crosstalk zone. Embryologically, the “ureteric bud” ultimately forms both the glomerulus and renal tubules (afferent arteriole [aA], efferent arteriole [eA], and proximal distal convoluted tubule [pDCT]) in utero. In addition, retinoic acid upregulates renin‐angiotensin‐aldosterone system gene expression. Specifically, embryologically and into adulthood, the kidney has a self‐contained dopamine system that can communicate with the body whereby “paracrine” effects are comodulated with intrarenal sodium balance. Therefore, renal dopaminergic tone (via D1 and D2 receptors) may be a culprit for thiazide resistance and a treatment target for patients with resistant essential hypertension
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References

    1. Sarafidis PA, Georgianos P, Bakris GL. Resistant hypertension–its identification and epidemiology. Nat Rev Nephrol. 2013;9:51–58. - PubMed
    1. Patlola RS. Resurrecting renal denervation research after the device industry gold rush. Cath Lab Digest. 2014;22.
    1. Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment. Circulation. 2008;117:e510. - PubMed
    1. Vert G, Chory J. Crosstalk in cellular signaling: background noise or the real thing? Dev Cell. 2011;21:985–991. - PMC - PubMed
    1. Guyton AC, Coleman TG. Long‐term regulation of the circulation: interrelationships with body fluid volumes. In: Reeve EB, Guyton AC, eds. Physical Bases of Circulatory Transport Regulation and Exchange. Philadelphia, PA: Saunders; 1967:179–201.

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