Navigation Links
Doubling down on heart failure: Researchers discover new route to disease, and drugs to match

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
University of Rochester Medical Center

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:
(Date:6/25/2016)... , ... June 25, 2016 , ... First Choice ... States, named Dr. Sesan Ogunleye, as the Medical Director of its new Mesquite-Samuell Farm ... Medical Director of our new Mesquite location,” said Dr. James M. Muzzarelli, Executive Medical ...
(Date:6/25/2016)... City, Oklahoma (PRWEB) , ... June 25, 2016 ... ... helping both athletes and non-athletes recover from injury. Recently, he has implemented orthobiologic ... the Oklahoma City area —Johnson is one of the first doctors to perform ...
(Date:6/25/2016)... Canada (PRWEB) , ... June 25, 2016 , ... Conventional ... pursuit of success. In terms of the latter, setting the bar too high can ... risk more than just slow progress toward their goal. , Research from ...
(Date:6/24/2016)... Marne, Michigan (PRWEB) , ... June 24, 2016 , ... ... To deal with these feelings, many turn to unhealthy avenues, such as drug or ... Center of Marne, Michigan, has released tools for healthy coping following a traumatic event. ...
(Date:6/24/2016)... ... ... in a crisis. Her son James, eight, was out of control. Prone to extreme mood ... something upset him, he couldn’t control his emotions,” remembers Marcy. “If there was a ... children and say he was going to kill them. If we were driving on ...
Breaking Medicine News(10 mins):
(Date:6/26/2016)... June 27, 2016  VMS Rehab Systems, Inc. ( ... take whatever measures required to build a strong and ... is currently listed on the OTC Markets-pink current trading ... and CEO, "We are seeing an anomaly in market ... not only by the Company, but shareholders and market ...
(Date:6/24/2016)... , June 24, 2016  Global Blood Therapeutics, ... company developing novel therapeutics for the treatment of ... announced the closing of its previously announced underwritten ... at the public offering price of $18.75 per ... were offered by GBT. GBT estimates net proceeds ...
(Date:6/24/2016)... ALEXANDRIA, Va. , June 24, 2016 ... a set of recommendations that would allow ... information (HCEI) with entities that make formulary and coverage ... determine the "value" of new medicines. The ... that does not appear on the drug label, a ...
Breaking Medicine Technology: