Contact

Department

Cellular and Integrative Physiology

Elena Mironova, Ph.D.

Instructor

Personal Statement:

I am a research instructor in the Dr. Stockand laboratory at the University of Texas Health San Antonio.  I have an established history of research on the cardiovascular system, ion channels, and epithelial transport as supported by numerous awards, presentations and publications.

 

In Dr. Stockand’s laboratory, I investigate the involvement of renal sodium channels in regulating blood pressure in an attempt to improve therapy for hypertension and heart disease.  Recently, I helped develop the isolated, split-open tubule preparation in the laboratory.  This tool is instrumental in measuring channel activity in native tissue allowing me to combine such measurements with whole animal studies quantifying systemic water and sodium handling.  This broad-based approach has allowed me to ask novel questions about the cardiovascular system and the role of renal sodium transport in this system that have opened new lines of investigation. In addition, it has enabled me to elucidate the cellular mechanism and understand the consequences of these mechanisms at the level of the whole animal.  For instance, by using this approach, I obtained compelling evidence of an inhibitory paracrine purinergic signaling system that is intrinsic to the distal nephron and necessary for the normal feedback regulation of blood pressure.  As I demonstrated, increases in urine flow evoke ATP release into the urine from intercalated cells.  This ATP activates P2Y2 metabotropic purinergic receptors in principal cells to decrease the activity of ENaC.  A consequence of this is that increases in dietary sodium intake increase renal sodium excretion through this mechanism enabling renal sodium handling to compensate for changes in sodium ingestion.  This is key to normal blood pressure regulation for as I have shown, genetic ablation of the P2Y2 receptor or the conduit for ATP release from intercalated cells increases blood pressure in a sodium-dependent manner. In addition to measuring channel activity in isolated rodent split-open tubule I pioneered similar measurements in native human tissue increasing translational potential of my work.

 

Recently, I have begun investigating into the role of ADH regulation of ENaC and renal sodium excretion.  The root of this inquiry is based on the counterintuitive observation that ADH increases ENaC activity but yet this increase in ENaC activity seems to facilitate urinary concentration and dilution of plasma rather than the expected increase in plasma sodium as predicted by ENaC being an end-effector of the renin-angiotensin-aldosterone system during control of blood volume and thus, pressure. My near-term goal is to understand the consequences of ADH regulation of ENaC and how this contributes to the regulation of plasma osmolality and volume and consequently blood pressure.


Education

State Technical University. St.-Petersburg, Russia B.S., M.S., 05/2003
Institute of Evolutionary Physiology and biochemistry. St.-Petersburg, Russia, Ph.D., 04/2007

Research

  1. Discretionary control of Na+ excretion is a key component of the regulation of arterial blood pressure in mammals. Sodium excretion is fine-tuned in the aldosterone-sensitive distal nephron by the activity of the epithelial Na+ channel (ENaC). Here, ENaC functions as a final effector of the renin-angiotensin-aldosterone system (RAAS) during negative feedback control of blood pressure. My following publications directly addressed the fact that robust inhibitory purinergic signaling system intrinsic to the distal nephron dynamically regulates ENaC through paracrine ATP signaling via the metabotropic P2Y2 purinergic receptor to properly match urinary Na+ excretion to the dietary Na+ intake. This enables blood pressure to be maintained within a normal range despite broad changes in dietary Na+ consumption. Such observations identify purinergic signaling as a possible therapeutic target for the treatment of elevated blood pressure particularly that associated with salt sensitivity.
  2. In addition to the contributions described above, with a team of collaborators, I found that the activity of ENaC in the distal nephron, surprisingly, is sustained high by ADH in states of water and electrolyte imbalance associated with suppressed aldosterone levels. I showed that ADH-mediated activation of ENaC facilitates urinary concentration and dilution of plasma.Specific inhibitors of ENaC provoke osmotic diuresis because inhibition of ENaC compromises urinary concentrating ability to some degree. The present findings may have important implications for the treatment of hyponatremia associated with high AVP levels such as in decompensated heart failure, cirrhosis, and syndrome of inappropriate antidiuretic hormone secretion. In these diseases, where hyponatremia is the clinical hallmark of the nonosmotic release of ADH, inhibition of ENaC may serve to counter hyponatremia at the same time as decreasing plasma volume.

Research Support

F32 DK104572 (Mironova)              12-01-2014 – 11-30-2017          12 calendar months
NIH/NIDDK                                               $60,000/year
Regulation of renal Na + excretion by antidiuretic hormone.

Specific Aims:  1) Determine the effective concentration of ADH on ENaC in health and pathological states; 2) Quantify the contribution of ADH-stimulated ENaC to systemic Na+ and water balance; 3) Understand the contribution of ADH-stimulated ENaC to pathological states of hypo- and hypernatremia.
Role: PI

Awards & Accomplishments

2007    IBRO-PENS student travel award
2009    UTHSCSA post-doctoral fellow travel award
2009    Co-Chairman for EB2009 “Renal Section- “Renal Ion Transport”
2010    UTHSCSA post-doctoral fellow travel award
2010    UTHSCSA post-doctoral fellow travel award
2012    APS Postdoctoral Excellence in Renal Research Finalist
2013    UTHSCSA physiology research symposium, postdoctoral fellow best poster award

Affiliations

2007    IBRO-PENS student travel award
2009    UTHSCSA post-doctoral fellow travel award
2009    Co-Chairman for EB2009 “Renal Section- “Renal Ion Transport”
2010    UTHSCSA post-doctoral fellow travel award
2010    UTHSCSA post-doctoral fellow travel award
2012    APS Postdoctoral Excellence in Renal Research Finalist
2013    UTHSCSA physiology research symposium, postdoctoral fellow best poster award

Publications

Mironova E, Lynch IJ, Berman JM, Gumz ML, Stockand JD, Wingo CS. ENaC activity in the cortical collecting duct of HKα1H+, K+-ATPase knockout mice is uncoupled from Na+ intake. American journal of physiology. Renal physiology. 2017; 312(6):F1073-F1080. PubMed [journal] PMID: 28179253

Mironova E, Chen Y, Pao AC, Roos KP, Kohan DE, Bugaj V, Stockand JD. Activation of ENaC by AVP contributes to the urinary concentrating mechanism and dilution of plasma. American journal of physiology. Renal physiology. 2015; 308(3):F237-43. PubMed [journal] PMID: 25391898, PMCID: PMC4596725

Mironova E, Boiko N, Bugaj V, Kucher V, Stockand JD. Regulation of Na+ excretion and arterial blood pressure by purinergic signalling intrinsic to the distal nephron: consequences and mechanisms. Acta physiologica (Oxford, England). 2015; 213(1):213-21. PubMed [journal] PMID: 25154328

Mironova E, Bugay V, Pochynyuk O, Staruschenko A, Stockand JD. Recording ion channels in isolated, split-opened tubules. Methods in molecular biology (Clifton, N.J.). 2013; 998:341-53. NIHMSID: NIHMS630072 PubMed [journal] PMID: 23529443, PMCID: PMC4181527

Mironova E, Bugaj V, Roos KP, Kohan DE, Stockand JD. Aldosterone-independent regulation of the epithelial Na+ channel (ENaC) by vasopressin in adrenalectomized mice. Proceedings of the National Academy of Sciences of the United States of America. 2012; 109(25):10095-100. PubMed [journal] PMID: 22665796, PMCID: PMC3382497

 

Complete List of Published Work in MyBibliography:

https://www.ncbi.nlm.nih.gov/myncbi/browse/collection/48236263/?sort=date&direction=descending