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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 proteinsthat plays a major role in the development of the disease. Thesecond but equally powerful hit: Drugs that interfere with thisaxis already exist. Though still in its infancy, the combination is just the type ofresearch the scientific community is looking for in its efforts tospeed up the development of the next generation of treatments forthe nation's biggest killers, of which heart disease is the long-reigning champ. Burns C. Blaxall, Ph.D., FAHA, of the University of RochesterMedical Center, led the research team to the discovery, whichrevolves around adrenaline, the hormone that regulates rate andstrength of the heart and causes our hearts to beat furiously in acrisis. Adrenaline levels are constantly ramped in people withheart failure - the body's attempt to recharge a weakened heart.While decades of research have established a connection betweenelevated adrenaline and heart failure, there is still much to learnabout how it contributes to the disease. In a mouse model of heart failure, Blaxall's team found thatchronically high levels of adrenaline spur a bad actor - a proteincalled PAR1 - into gear. Several years ago, collaborative work inBlaxall's laboratory showed that over-stimulating PAR1 in cardiacmuscle cells leads to heart failure, while blocking it protectsagainst the disease. But, like most processes in the body, adrenaline doesn't drive PAR1on its own; the team discovered it tags a middleman - anotherprotein, called MMP-13 - which then prompts activation of PAR1 towreak havoc in the heart. "This research is very exciting because we've identified acompletely new pathway activated by adrenaline that contributes toheart failure," said Blaxall, an associate professor at the AabCardiovascular Research Institute at the Medical Center. Even more exciting, the team demonstrated that targeting eitherprotein in the pathway - removing PAR1 or inhibiting MMP-13 -prevented cardiac dysfunction in mice, suggesting that drugsdirected at either may hold promise for the treatment of heartdisease. "Our idea going forward is that in addition to blocking the effectsof adrenaline, which is what beta blockers were designed to do, it may be wise to also inhibit MMP-13, orPAR1, or both, to help patients with heart failure," noted Blaxall. Potential drug candidates are already available. Inhibitors ofMMP-13 are currently under evaluation, mostly as a potentialtreatment for rheumatoid arthritis and osteoarthritis, where MMP-13 has been shown to play a role inthe development of each condition. Additionally, drugs that blockPAR1 have been tested as antiplatelet agents - drugs that stopblood clots from forming - in large-scale clinical trials. Blaxall says that in the future he plans to test drugs like thesein animal models of heart failure. This strategy is in line with work being done by the NationalCenter for Advancing Translational Sciences (NCATS) at the NationalInstitutes of Health, established in 2011 to address the gapbetween basic research findings and new treatments for patients.The center is encouraging researchers to focus on compounds thathave already cleared key steps in the development process,including safety testing, as they work to develop new therapies. Additional References Citations. We are high quality suppliers, our products such as Hydraulic Pressure Valve , Hydraulic Axial Pump for oversee buyer. To know more, please visits Kayaba Pumps.
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