The longevity gene mammalian Indy (mINDY) is involved in blood pressure regulation

January 26, 2021

Authors from the German Center for Diabetes Research (DZD) presented data showing that the longevity gene mammalian Indy (mINDY) is involved in blood pressure regulation in the Journal of Clinical Investigation (JCI) insight. Reduced expression of mINDY, which is known to extend life span in lower organisms and to prevent from diet induced obesity, fatty liver and insulin resistance in mice, has now been shown to lower blood pressure and heart rate in rodents. The authors provided mechanistic insights for the underlying physiological mechanism based on in vivo data in a genetic knock out model as well as microarray and in vitro studies. Furthermore, the hypothesis is supported by confirming critical effects in vitro using a small molecule inhibitor of mINDY. The authors conclude that deletion of mIndy recapitulates beneficial cardiovascular and metabolic responses to caloric restriction, making it an attractive therapeutic target.

Andreas Birkenfeld and colleagues provide a comprehensive study showing that mIndy deletion attenuates sympathoadrenal support of blood pressure and reduced arterial blood pressure and heart rate in a muine knockout model. Blood pressure was assessed invasively using intra-arterial pressure probes over several days. Urinary analysis for catecholamines and metanephrines as well as unbiased transcriptomic analysis of adrenal glands identified the affected biosynthetic pathways. Indeed, catecholamine biosynthesis was attenuated in mINDY-KO adrenals, whereas plasma steroids and steroid hormone synthesis were unaffected.

In vitro studies on an adrenal cell line supported this hypothesis. mIndy codes for a is a carboxylic acid transporter protein expressed in plasma membrane. Citrate, the main substrate of the mINDY transporter, increased catecholamine content, while pharmacological inhibition of mINDY by a small molecule inhibitor blunted the effect.

The study provided further insights into the physiological mechanisms of the beneficial effects of reducing mINDY activity which is known to protect from diet and aging induced metabolic diseases by mechanisms akin to caloric restriction. Therefore, the data showed a novel mechanism contributing to a cardiometabolic cross talk and further supporting mINDY as a promising target for the whole spectrum of metabolic syndrome components, including increased blood pressure.
-end-
The study was published from the Institute of Diabetes Research and Metabolic Disorders (IDM) of the Helmholtz Center Munich at the University Tübingen and the Clinic of Diabetes, Endocrinology and Nephrology of the University Hospital Tübingen.

Publication:
Willmes DM, Daniels MA, Kurzbach A, Lieske S, Bechmann N, Schumann T, Henke C, El-Agroudy N, Da Costa Goncalves AC, Peitzsch M, Hofmann A, Kanczkowski W, Kräker K, Mu?ller DN, Morawietz H, Deussen A, Wagner M, El-Armouche A, Helfand SL, Bornstein SR, de Cabo R, Bernier M, Eisenhofer G, Tank J, Jordan J, Birkenfeld AL. The longevity gene mIndy (I'm Not Dead, Yet) affects blood pressure through sympathoadrenal mechanisms. JCI Insight. 2021, https://doi.org/10.1172/jci.insight.136083.

Contact:

Prof. Andreas L. Birkenfeld
German Center for Diabetes Research
Department of Internal Medicine IV
Tübingen University Hospital
Otfried-Müller-Str. 10, 72076 Tübingen, Germany
Phone: +49 (0)7071 29-82735
Email: andreas.birkenfeld@med.uni-tuebingen.de

The German Center for Diabetes Research (DZD) is one of six German Centers for Health Research. It brings together experts in the field of diabetes research and integrates basic research, epidemiology, and clinical applications. By adopting an innovative, integrative approach to research, the DZD aims to make a substantial contribution to the successful personalized prevention, diagnosis and treatment of diabetes mellitus. The members of the DZD are Helmholtz Zentrum München - German Research Center for Environmental Health, the German Diabetes Center (DDZ) in Düsseldorf, the German Institute of Human Nutrition (DIfE) in Potsdam-Rehbrücke, the Institute of Diabetes Research and Metabolic Diseases of Helmholtz Zentrum München at the University of Tübingen, the Paul Langerhans Institute Dresden of Helmholtz Zentrum München at the Carl Gustav Carus University Hospital of TU Dresden, associated partners at the universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich, and other project partners. http://www.dzd-ev.de/en

Deutsches Zentrum fuer Diabetesforschung DZD

Related Blood Pressure Articles from Brightsurf:

Children who take steroids at increased risk for diabetes, high blood pressure, blood clots
Children who take oral steroids to treat asthma or autoimmune diseases have an increased risk of diabetes, high blood pressure, and blood clots, according to Rutgers researchers.

High blood pressure treatment linked to less risk for drop in blood pressure upon standing
Treatment to lower blood pressure did not increase and may decrease the risk of extreme drops in blood pressure upon standing from a sitting position.

Changes in blood pressure control over 2 decades among US adults with high blood pressure
National survey data were used to examine how blood pressure control changed overall among U.S. adults with high blood pressure between 1999-2000 and 2017-2018 and by age, race, insurance type and access to health care.

Transient increase in blood pressure promotes some blood vessel growth
Blood vessels are the body's transportation system, carrying oxygen and nutrients to cells and whisking away waste.

Effect of reducing blood pressure medications on blood pressure control in older adults
Whether the amount of blood pressure medications taken by older adults could be reduced safely and without a significant change in short-term blood pressure control was the objective of this randomized clinical trial that included 534 adults 80 and older.

Brain blood flow sensor discovery could aid treatments for high blood pressure & dementia
A study led by researchers at UCL has discovered the mechanism that allows the brain to monitor its own blood supply, a finding in rats which may help to find new treatments for human conditions including hypertension (high blood pressure) and dementia.

Here's something that will raise your blood pressure
The apelin receptor (APJ) has been presumed to play an important role in the contraction of blood vessels involved in blood pressure regulation.

New strategy for treating high blood pressure
The key to treating blood pressure might lie in people who are 'resistant' to developing high blood pressure even when they eat high salt diets, shows new research published today in Experimental Physiology.

Arm cuff blood pressure measurements may fall short for predicting heart disease risk in some people with resistant high blood pressure
A measurement of central blood pressure in people with difficult-to-treat high blood pressure could help reduce risk of heart disease better than traditional arm cuff readings for some patients, according to preliminary research presented at the American Heart Association's Hypertension 2019 Scientific Sessions.

Heating pads may lower blood pressure in people with high blood pressure when lying down
In people with supine hypertension due to autonomic failure, a condition that increases blood pressure when lying down, overnight heat therapy significantly decreased systolic blood pressure compared to a placebo.

Read More: Blood Pressure News and Blood Pressure Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.