Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein Overexpression at Heart of Heart Failure

14.03.2007
Chronic heart failure resulting from dilated cardiomyopathy is rapidly emerging as a disease of epidemic proportions.1 Molecular mechanisms are being studied and advances have been made in a minority of cases, e.g.: the familial forms.

Intracellular [Ca2+]i homeostasis is essential for normal cardiac function and integrity, and dysregulation of [Ca2+]i is a hallmark of advanced heart failure.2 The primary trigger for cardiac [Ca2+]i transients is calcium entry through the pore subunit of the voltage-dependent L-type channels (L-VDCC), but their role in heart failure is still controversial. Electrophysiological studies on individual L-VDCCs from failing human heart have revealed an increased single-channel activity but the mechanism for this biophysical phenotype has remained unknown.3,4

In a paper in this week’s PLoS ONE, Roger Hullin of the Swiss Heart Center Bern, Jan Matthes of University of Cologne, Germany, and collaborators in both Germany and the USA demonstrate an up-regulation of expression of an accessory subunit of the L-VDCC complex (beta 2-subunit) that is responsible for the altered channel behavior in human heart failure. Similar changes of both beta 2-subunit expression and single-channel behavior were also observed in a mouse model of heart failure with cardiac overexpression of the human L-type Ca2+-channel pore. The causal role of the increased beta 2-subunit expression for the “heart failure type” of single L-VDCC characteristics was proven when the authors developed a novel, cardiac-specific, drug-inducible beta 2a subunit overexpression transgenic mouse which was crossbred with the channel pore overexpressing mouse when still nonfailing (“Adaptive phase”). In the nonfailing double transgenics, the induction of beta 2a protein expression increased the activity of single ventricular L-VDCC, rendering these channels phenotypically identical to human and mouse heart failure.

The authors conclude that electrical remodeling of the L-VDCC, based on gene expression changes, is an early step in a cascade ultimately induced in heart failure. This provides a rational framework for novel therapeutic intervention in heart failure.

... more about:
»L-VDCC »L-type »beta »heart failure
REFERENCES
1.Kannel WB (2000) Incidence and epidemiology of heart failure. Heart Fail Rev 5: 167-73.
2.Sjaastad I et al. (2003) Heart failure - a challenge to our current concepts of excitation-contraction coupling. J Physiol 546: 33-47.
3.Schroeder F et al. (1998) Increased availability and open probability of single L-type calcium channels from failing compared with nonfailing human ventricle. Circulation 98: 969-76.

4.Bodi I et al. (2005) The L-type calcium channel in the heart: the beat goes on. J Clin Invest 115: 3306-17.

Andrew Hyde | alfa
Further information:
http://www.plosone.org
http://dx.doi.org/10.1371/journal.pone.0000292

Further reports about: L-VDCC L-type beta heart failure

More articles from Life Sciences:

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

Quantum optical sensor for the first time tested in space – with a laser system from Berlin

23.01.2017 | Physics and Astronomy

The interactome of infected neural cells reveals new therapeutic targets for Zika

23.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>