Researchers to Discuss Hormonal and Sodium-related Factors of Cardiovascular Disease at APS Conference

Rockville, Md. (September 25, 2019)—International physiologists and researchers studying the kidney, high blood pressure and related medical conditions will convene next week at the American Physiological Society (APS) Aldosterone and ENaC in Health and Disease: The Kidney and Beyond Conference in Estes Park, Colo.

The number of people with obesity, age-related high blood pressure and heart failure is steadily increasing. The rise in these chronic health conditions highlights the importance of understanding the drivers of heart disease, including aldosterone—a mineralocorticoid hormone produced by the adrenal glands—and its relationship with the epithelial sodium channel (ENaC) and mineralocorticoid receptor (MR). ENaC is an ion channel located on cell membranes that forms a pathway for sodium reabsorption in the kidneys. MR is a protein that binds to aldosterone, an important regulator of ENaC. Together, they regulate the body’s balance of salt and water.

“Elevated aldosterone and activation of mineralocorticoid receptors is increasingly common in growing populations with heart failure, high blood pressure and obesity. In these populations, elevated aldosterone is associated with increased risk of heart attack, stroke and cardiovascular death,” said conference co-organizer Iris Jaffe, MD, PhD, of Tufts Medical Center in Boston. “This conference summarizes state-of-the-art understanding of the mechanisms driving inappropriate aldosterone release and [its] impact on the heart, lung, kidneys, blood vessels and [other organs],” Jaffe said.

“It brings together scientists from two complementary fields (aldosterone/MR and ENaC) and from across the spectrum of basic to clinical research. In this way, the conference facilitates synergies and new interactions that advance the research in these fields,” added conference co-organizer Peter Snyder, MD, of the University of Iowa.

Topics “will cover new and exciting discoveries in ENaC [such as] the recently solved three-dimension structure of ENaC and the development of mini kidneys (kidney organoids) for clinical research” said conference co-organizer Daniela Rotin, PhD, of the Hospital for Sick Children and University of Toronto in Canada.

Conference goals include learning more about the basic biology of these molecules, their role in kidney function and blood pressure, and the patients who would benefit most from emerging treatments. The program will include research-based sessions, abstract-driven presentations and poster sessions.

Program Highlights

Wednesday, October 2

Keynote Lecture: Human kidney organoids

Chair: Daniela Rotin, PhDHospital for Sick Children and University of Toronto, Canada

Speaker: Joseph Bonventre, MD, PhDHarvard University, Cambridge, Mass.

 

Thursday, October 3

Symposium 1A: Aldosterone and mineralocorticoid receptors in the kidney and hypertension

Chairs: David Calhoun, MDUniversity of Alabama, Birmingham; Celso Gomez-Sanchez, MDUniversity of Mississippi

Speakers:

“MR activation by Rac1 in kidney disease”

Toshiro Fujita, MD, PhDUniversity of Tokyo, Japan

 

“The expanding spectrum of primary aldosteronism”

Anand Vaidya, MDBrigham and Women’s Hospital and Harvard Medical School, Boston

 

“The intercalated cell mineralocorticoid receptor regulates pendrin directly and regulates principal cell ENaC indirectly over a wide range in serum K+”

Susan Wall, MDEmory University, Atlanta

 

“Kir5.1-mediated changes in renin-angiotensin-aldosterone system balance in salt sensitive hypertension”

Anna Manis, Medical College of Wisconsin

 

“A proof-of-principle study of sodium loading in prehypertension”

J. Brian Byrd, MDUniversity of Michigan Medical School

 

Symposium 1B: Metabolic and sex differences in aldosterone responses

Chairs: Massi Caprio, MD, PhDIstituto di Ricerca e Cura a Catterere Scientifico (IRCCS), ItalyJames Luther, MDVanderbilt University, Nashville, Tenn.

 

Speakers:

“Biological sex-specific differences in the aldosterone responses to angiotensin II in humans and rodents”

Jose Romero, PhDBrigham and Women’s Hospital and Harvard Medical School, Boston

 

“The Leptin-aldosterone-mineralocorticoid receptor axis: a major contributor to cardiovascular disease in obese females”

Eric Belin de Chantemèle, PhDAugusta University, Georgia

 

“Hypersensitivity of renal ENaC to aldosterone is a sex-specific determinant of blood pressure control in females”

Mykola Mamenko, PhDAugusta University, Georgia

 

“Female mice exhibit higher increases in aldosterone synthase expression and aldosterone production than males in response to low-salt diet”

Jessica Faulkner, PhDMedical College of Georgia at Augusta University

 

Symposium 2A: Structure function of ENaC and related transporters

Chairs: Peter Snyder, MDUniversity of Iowa; Bernard Rossier, MD, University of Lausanne, Switzerland

 

Speakers:

“ENaC structure by cryo-electron microscopy”

Isabelle Baconguis, PhDOregon Health and Science University

 

“ENaC gating regulation by biliary factors”

Ossama Kashlan, PhDUniversity of Pittsburgh

 

“ENaC subunit N-glycans have different roles for the ability of the channel to respond to shear force”

Martin Fronius, PhDUniversity of Otago, New Zealand

 

“N-methyl-D-aspartate (NMDA) receptor interacts with ENaC to induce renal vasodilation in the connecting tubule”

Cesar Romero, PhDEmory University School of Medicine, Atlanta

 

“Proton block of the epithelial sodium channel”

Daniel Collier, PhDUniversity of Tennessee Health Science Center

 

Symposium 2B: ENaC function and regulation in tissues

Chairs: Lawrence Palmer, PhDCornell University, New York; Edith Hummler, PhD, University of Lausanne, Switzerland

 

Speakers:

“Regulation of ENaC by extracellular Na”

Thomas Kleyman, MD, University of Pittsburgh

 

“ENaC Regulation by aldosterone and proteases”

Christoph Korbmacher, MDFriedrich-Alexander University of Erlangen-Nürnberg, Germany

 

“Potassium sensing in the distal nephron”

David Penton Ribas, PhDUniversity of Zurich, Switzerland

 

“The hypertension pandemic: an evolutionary perspective”

Bernard Rossier, MD, University of Lausanne, Switzerland

 

Friday, October 4

Symposium 3A: Signaling and regulation of ENaC and other epithelial channels/transporters I

Chair: Doug Eaton, PhDEmory University, Atlanta

 

Speakers:

“ENaC regulation by the mTORC2-SGK1 signaling module”

David Pearce, MDUniversity of California, San Francisco

 

“Role of microRNAs in aldosterone signaling and ENaC regulation”

Michael Butterworth, PhDUniversity of Pittsburgh

 

“AMPK regulates ENaC via a tripartite inhibitory complex”

Kenneth Hallows, MD, PhDUniversity of Southern California

 

“Elevated sodium activates the NLRP3 inflammasome in antigen presenting cells through an ENaC-dependent mechanism”

Ashley Pitzer, PhDVanderbilt University Medical Center, Nashville, Tenn.

 

“Postprandial effects on ENaC-mediated sodium absorption”

Christine Klemens, PhDMedical College of Wisconsin

 

Symposium 3B: Signaling and regulation of ENaC and other epithelial channels/transporters II

Chairs: Alexander Staruschenko, PhDMedical College of WisconsinJim Stockand, PhDUniversity of Texas, San Antonio

 

Speakers:

“WNK kinases and cell volume regulation”

Arohan Subramanya, MDUniversity of Pittsburgh

 

“From SPLUNC1 to SPX-101, novel peptidomimetics to treat sodium hyperabsorption in the CF lung”

Robert Tarran, PhDUniversity of North Carolina

 

“Direct effect of potassium on ENaC regulation and potassium secretion in collecting duct cells: role of mTORC2/SGK1 signaling”

Bidisha Saha, PhDUniversity of California, San Francisco

 

“High mobility group box-1 protein regulates lung epithelial sodium channel activity via the receptor for advanced glycation end products”

Garett GrantUniversity of Utah

 

Symposium 4A: ENaC biogenesis and trafficking

Chair: Daniela Rotin, PhDHospital for Sick Children and University of Toronto, Canada

 

Speakers:

“Novel mechanisms of diuretic resistance revealed by single cell analysis”

Vivek Bhalla, MDStanford University School of Medicine, California

 

“Regulation of renal ion transport by ubiquitylation and phosphorylation networks”

Olivier Staub, PhDUniversity of Lausanne, Switzerland

 

“Regulation of ENaC by the ER lumenal, molecular chaperone, GRP170”

Teresa Buck, PhDUniversity of Pittsburgh

 

“A conserved region in the N-terminus of alpha-ENaC regulates proteolytic processing during anterograde transport”

Pradeep Kota, PhDUniversity of North Carolina at Chapel Hill

 

Saturday, October 5

Symposium 5A: MR in the vasculature

Chairs: Frederic Jaisser, MD, PhDInstitut Nationale de la Santé et de la Recherche Médicale (INSERM), France; Iris Jaffe, MD, PhDTufts Medical Center, Boston

 

Speakers:

“Sex-specific mechanisms of resistance vessel endothelial dysfunction in obesity”

Ana Davel, PhDUniversity of Campinas, Brazil

 

“Sex differences in the role of the smooth muscle cell mineralocorticoid receptor in cardiovascular aging”

Jennifer DuPont, PhDTufts Medical Center, Boston

 

“Role of the myeloid mineralocorticoid receptor in vascular inflammation in atherosclerosis”

Joshua ManTufts Medical Center, Boston

 

“Aldosterone and angiotensin II increase aortic stiffness and endothelial dysfunction via an action of oxidative stress on the endothelial sodium channel”

James Sowers, MDUniversity of Missouri

 

“The novel non-steroidal MR antagonist finerenone improves metabolic parameters via ATGL-mediated lipolysis of brown adipose tissue in high-fat diet fed mice”

Vincenzo Marzolla, PhDIRCCS, Italy

 

Symposium 5B: MR structure and role in the heart and lungs

Chairs: Gail Adler, MD, PhDBrigham and Women’s Hospital, Boston; Shawn Bender, PhDUniversity of Missouri

 

Speakers:

“Enhanced endothelium epithelial sodium channel signaling prompts left ventricular diastolic dysfunction in obese female mice”

Guanghong Jia, PhDUniversity of Missouri School of Medicine

 

“Structural determinants of activation of the mineralocorticoid receptor: an evolutionary perspective”

Peter Fuller, MD, PhDHudson Institute of Medical Research, Australia

 

“The quaternary structure of the mineralocorticoid receptor depends on ligand and DNA binding”

Diego Alvarez de la RosaPhDUniversidad de La Laguna, Spain

 

“Vascular cell-specific roles of mineralocorticoid receptors in pulmonary hypertension”

Ioana Preston, MDTufts Medical Center, Boston

 

Clinical Plenary Lecture

Chair: Maria-Christina Zennaro, MD, PhDParis Cardiovascular Research Center, France

 

Speaker:

“The role of non-steroidal MR antagonists and new potassium binders for the treatment of cardiovascular disease”

Bertram Pitt, MDUniversity of Michigan

 

Sunday, October 6

Symposium 6A: Normal and pathogenic regulation of aldosterone biosynthesis

Chairs: Eleanor Davies, PhDUniversity of Glasgow, Scotland; Jun Yang, PhDMonash University, Australia

 

Speakers:

“Development of an inducible mouse model of aldosteronism”

William Rainey, PhDUniversity of Michigan

 

“A gain of function mutation in CLCN2 chloride channel gene causes primary aldosteronism”

Fabio Fernandes-Rosa, PhDINSERM U970, France

 

“Circulating microRNAs as diagnostic biomarkers of primary aldosteronism”

Eleanor Davies, PhDUniversity of Glasgow, Scotland

 

“The retinoic acid receptor a contributes to the development of primary aldosteronism by regulating adrenal cortex structure through interactions with Wnt and Vegfa signaling”

Sheerazed Boulkroun, PhDINSERM U970, France

 

Symposium 6B: Integrated regulation of renal ion transport

Chairs: David Ellison, MD, Oregon Health Science University; Johannes Loffing, MDUniversity of Zurich, Switzerland

 

Speakers:

“The role of ENaC in hyperoxia-induced preterm lung injury”

My Helms, PhDUniversity of Utah

 

“Regulation of renal ion transport and blood pressure by the CRL3-WNK-SPAK pathway”

James McCormick, PhDOregon Health and Science University

 

“WNK regulation of ion transport in the malpighian tubule”

Aylin Rodan, PhDUniversity of Utah

 

“Interleukin 6 activation of the epithelial sodium channel in the distal convoluted tubule and cortical collecting duct via Rac1”

Oishi PaulEmory University, Atlanta

NOTE TO JOURNALISTS: The APS Aldosterone and ENaC in Health and Disease: The Kidney and Beyond Conference will be held October 2–6 in Estes Park, Colo. To schedule an interview with the conference organizers or presenters, contact the APS Communications Office or call 301.634.7314. Find more research highlights in the APS News Room.

Physiology is the study of how molecules, cells, tissues and organs function in health and disease. Established in 1887, the American Physiological Society (APS) was the first U.S. society in the biomedical sciences field. The Society represents more than 10,000 members and publishes 15 peer-reviewed journals with a worldwide readership.

 

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