An often overlooked protein actually a potent regulator of cardiac hypertrophy

November 16, 2009

(PHILADELPHIA) A protein long thought to be a secondary regulator in the heart's response to stressors like hypertension actually appears to be a primary regulator according to researchers from the Center for Translational Medicine at Thomas Jefferson University. The data will be presented in the Late Breaking Science session at the American Heart Associations Scientific Sessions in Orlando, Fla.

According to Thomas Force, M.D., the James C. Wilson Professor of Medicine at Jefferson Medical College of Thomas Jefferson University, glycogen synthase kinase-3 (GSK-3) proteins include the isoforms GSK-3beta and GSK-3alpha. GSK-3beta has always been thought to be the regulator of cardiac hypertrophy, and GSK-3alpha has been largely ignored. But the ignored isoform is actually quite powerful.

"We found that knocking out GSK-3beta did not do much at all, but knocking out of GSK-3alpha caused a huge increase in hypertrophy," said Dr. Force, who led the study. "The standard theory was that beta is more potent than alpha, but alpha was far more important at regulating this process."

Hypertrophy is the heart's response to stressors such as hypertension. In hypertrophy, the heart muscle cells get larger, as does the heart itself. This process is a predictor of heart failure and death. The concept, according to Dr. Force, is to understand the pathways through which this happens, which would allow physicians to intervene and possibly prevent the heart failure.

In addition to regulating hypertrophy, the researchers also found that GSK-3alpha is a potent positive regulator of the beta-adrenergic system, which allows the heart to respond to stresses and helps failing hearts pump better. But when GSK-3alpha was knocked out in the mice models, the heart systems simply failed and were not able to stand up to the pressure of stressors like hypertension.

GSK-3 is targeted by a number of drugs in development for several diseases, including bipolar disorder, Alzheimer's disease and diabetes.

"If these inhibitors make it to clinical trials, patients being treated with them would need to be closely watched, especially if they have diseases like hypertension or underlying heart disease," Dr. Force said. "They could run into trouble if their hearts are unable to respond to stressors due to the inhibition of GSK-3alpha."

Lastly, the researchers also found that when GSK-3beta was knocked out, the heart progenitor cells started to proliferate. This could potentially serve as the basis for a regenerative therapy approach for patients with heart failure, according to Dr. Force. Inhibiting GSK-3beta increased the proliferation of myocytes in the heart by five- to 10-fold.
-end-


Thomas Jefferson University

Related Heart Failure Articles from Brightsurf:

Top Science Tip Sheet on heart failure, heart muscle cells, heart attack and atrial fibrillation results
Newly discovered pathway may have potential for treating heart failure - New research model helps predict heart muscle cells' impact on heart function after injury - New mass spectrometry approach generates libraries of glycans in human heart tissue - Understanding heart damage after heart attack and treatment may provide clues for prevention - Understanding atrial fibrillation's effects on heart cells may help find treatments - New research may lead to therapy for heart failure caused by ICI cancer medication

Machining the heart: New predictor for helping to beat chronic heart failure
Researchers from Kanazawa University have used machine learning to predict which classes of chronic heart failure patients are most likely to experience heart failure death, and which are most likely to develop an arrhythmic death or sudden cardiac death.

Heart attacks, heart failure, stroke: COVID-19's dangerous cardiovascular complications
A new guide from emergency medicine doctors details the potentially deadly cardiovascular complications COVID-19 can cause.

Autoimmunity-associated heart dilation tied to heart-failure risk in type 1 diabetes
In people with type 1 diabetes without known cardiovascular disease, the presence of autoantibodies against heart muscle proteins was associated with cardiac magnetic resonance (CMR) imaging evidence of increased volume of the left ventricle (the heart's main pumping chamber), increased muscle mass, and reduced pumping function (ejection fraction), features that are associated with higher risk of failure in the general population

Transcendental Meditation prevents abnormal enlargement of the heart, reduces chronic heart failure
A randomized controlled study recently published in the Hypertension issue of Ethnicity & Disease found the Transcendental Meditation (TM) technique helps prevent abnormal enlargement of the heart compared to health education (HE) controls.

Beta blocker use identified as hospitalization risk factor in 'stiff heart' heart failure
A new study links the use of beta-blockers to heart failure hospitalizations among those with the common 'stiff heart' heart failure subtype.

Type 2 diabetes may affect heart structure and increase complications and death among heart failure patients of Asian ethnicity
The combination of heart failure and Type 2 diabetes can lead to structural changes in the heart, poorer quality of life and increased risk of death, according to a multi-country study in Asia.

Preventive drug therapy may increase right-sided heart failure risk in patients who receive heart devices
Patients treated preemptively with drugs to reduce the risk of right-sided heart failure after heart device implantation may experience the opposite effect and develop heart failure and post-operative bleeding more often than patients not receiving the drugs.

How the enzyme lipoxygenase drives heart failure after heart attacks
Heart failure after a heart attack is a global epidemic leading to heart failure pathology.

Novel heart pump shows superior outcomes in advanced heart failure
Severely ill patients with advanced heart failure who received a novel heart pump -- the HeartMate 3 left ventricular assist device (LVAD) -- suffered significantly fewer strokes, pump-related blood clots and bleeding episodes after two years, compared with similar patients who received an older, more established pump, according to research presented at the American College of Cardiology's 68th Annual Scientific Session.

Read More: Heart Failure News and Heart Failure 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.