Navigation Links
Doubling down on heart failure: Researchers discover new route to disease, and drugs to match
Date:6/7/2012

A new study in the journal Circulation packs a powerful one-two punch in the fight against heart failure. The leading blow: Identification of a unique alliance of proteins that plays a major role in the development of the disease. The second but equally powerful hit: Drugs that interfere with this axis already exist.

Though still in its infancy, the combination is just the type of research the scientific community is looking for in its efforts to speed up the development of the next generation of treatments for the nation's biggest killers, of which heart disease is the long-reigning champ.

Burns C. Blaxall, Ph.D., FAHA, of the University of Rochester Medical Center, led the research team to the discovery, which revolves around adrenaline, the hormone that regulates rate and strength of the heart and causes our hearts to beat furiously in a crisis. Adrenaline levels are constantly ramped in people with heart failure the body's attempt to recharge a weakened heart. While decades of research have established a connection between elevated adrenaline and heart failure, there is still much to learn about how it contributes to the disease.

In a mouse model of heart failure, Blaxall's team found that chronically high levels of adrenaline spur a bad actor a protein called PAR1 into gear. Several years ago, collaborative work in Blaxall's laboratory showed that over-stimulating PAR1 in cardiac muscle cells leads to heart failure, while blocking it protects against the disease.

But, like most processes in the body, adrenaline doesn't drive PAR1 on its own; the team discovered it tags a middleman another protein, called MMP-13 which then prompts activation of PAR1 to wreak havoc in the heart.

"This research is very exciting because we've identified a completely new pathway activated by adrenaline that contributes to heart failure," said Blaxall, an associate professor at the Aab Cardiovascular Research Institute at the Medical Center.

Even more exciting, the team demonstrated that targeting either protein in the pathway removing PAR1 or inhibiting MMP-13 prevented cardiac dysfunction in mice, suggesting that drugs directed at either may hold promise for the treatment of heart disease.

"Our idea going forward is that in addition to blocking the effects of adrenaline, which is what beta blockers were designed to do, it may be wise to also inhibit MMP13, or PAR1, or both, to help patients with heart failure," noted Blaxall.

Potential drug candidates are already available. Inhibitors of MMP-13 are currently under evaluation, mostly as a potential treatment for rheumatoid arthritis and osteoarthritis, where MMP-13 has been shown to play a role in the development of each condition. Additionally, drugs that block PAR1 have been tested as antiplatelet agents drugs that stop blood clots from forming in large-scale clinical trials.

Blaxall says that in the future he plans to test drugs like these in animal models of heart failure.

This strategy is in line with work being done by the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health, established in 2011 to address the gap between basic research findings and new treatments for patients. The center is encouraging researchers to focus on compounds that have already cleared key steps in the development process, including safety testing, as they work to develop new therapies.


'/>"/>
Contact: Emily Boynton
emily_boynton@urmc.rochester.edu
585-273-1757
University of Rochester Medical Center
Source:Eurekalert

Related medicine news :

1. Witnessing, Experiencing Traumatic Events May Worsen Heart Disease
2. Risk of suicide and fatal heart attack immediately following a cancer diagnosis
3. Cancer Diagnosis May Raise Odds for Suicide, Heart Attack Death
4. In children born with severe heart defect, surgical management has little effect on neuro outcomes
5. Invasive heart test being dramatically overused, Stanford study shows
6. Heart failure patients with diabetes may benefit from higher glucose levels
7. Omega-3 Supplements No Help Against Repeat Heart Trouble: Review
8. EKG Heart Test May Predict Risk in Older Adults
9. Common Blood Pressure Drug Safe for Heart Failure: Study
10. Spouses of Cancer Patients May Have Raised Risk of Heart Disease, Stroke
11. SMART heart eases heart ache, targets cardiac patients emotional well-being
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/12/2016)... ... February 12, 2016 , ... Young Asset Protection, a ... beginning of the latest charity campaign in their community enrichment program. Art Expression ... this worthy cause are currently being accepted at: http://artexpressioninc.org/ . , Art ...
(Date:2/12/2016)... ... February 12, 2016 , ... For Coast Dental dentist Everet Lake, ... and dental assistant Terrell Moore shortly before 7 a.m. to volunteer at Friday’s Dentistry ... donating their time and skills to help hundreds of uninsured and underinsured people receive ...
(Date:2/12/2016)... ... February 12, 2016 , ... ... choices that promote eye health. These articles generally list between five and 15 ... advocate Sharon Kleyne endorses every one of these lists and believes that nutritious ...
(Date:2/12/2016)... ... February 12, 2016 , ... US Sport Camps is pleased to announce the ... in Norwalk, serves as the host site and directing the camps is PGA Professional ... had successful camps in recent years around Des Moines and are fortunate to have ...
(Date:2/12/2016)... Calif. (PRWEB) , ... February 12, 2016 , ... The Central Coast Autism Spectrum Center ... dance is to provide a night of fun for teens with and without special needs ... feel welcomed and included at the event. The dance will take place on Saturday, Feb. ...
Breaking Medicine News(10 mins):
(Date:2/12/2016)... /PRNewswire/ - Demers Ambulances announces its first delivery in the state ... County Emergency Medical Services (EMS) consisting of four ... van. Quality Emergency Vehicles in Lecanto, FL ... This is the latest in Demers, ongoing expansion of sales.  ... Demers. --> Benoit LaFortune , Executive Vice President ...
(Date:2/12/2016)... 12, 2016 ... http://www.sedar.com ) und der ... abrufbar.    --> http://www.sedar.com ) ... http://www.telestatherapeutics.com abrufbar.    --> ... seinen Konzernabschluss des zweiten Quartals und ...
(Date:2/12/2016)... , Feb. 12, 2016   HeartWare International, ... conference call and webcast to discuss its financial results ... 2015, on Thursday, February 25, 2016 at 8:00 a.m. ... prior to the conference call and webcast.  On the ... financial results, highlights from the fourth quarter and business ...
Breaking Medicine Technology: