Researchers Discover Protein That Can Prevent Pulmonary Hypertension-Related Heart Failure

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Heart Failure

Heart FailureRegeneRx Biopharmaceuticals, Inc. announced a recent study where company’s scientists demonstrated that Thymosin beta 4 (TB4) can reduce or even prevent heart failure in a pulmonary hypertension mouse model. The study, entitled “Thymosin Beta 4 protects mice from monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy,” was published in the journal Plos One.

Pulmonary hypertension (PH) is characterized by increased blood pressure in lungs’ vasculature. Thus, so that blood flow can progress, the heart makes an extra effort to pump the blood to the lungs. As a consequence, the extra workload performed by the heart induces hypertrophy in the heart’s right ventricle, causing right heart failure. Standard therapeutics to reverse vascular remodeling and thereby prevent the risk of heart failure are currently limited. In this study, the authors aimed to determine the effect of Thymosin beta-4 (Tβ4), a 43-amino acid actin-binding protein with multiple-therapeutic protective effects, including cardiac repair in PH. They showed using monocrotaline (MCT)-induced PH mouse model, when administered with Tβ4 exhibited a significant reduction in systolic pressure and right ventricular hypertrophy, when compared to control mice.

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The researchers performed further studies, and identified that Tβ4 targets specific genes – Notch3, Col 3a and CTGF – and protects both lungs and heart from the damage induced by monocrotaline (MCT) administration.

Dr. Sudhirajan Gupta, the senior author and researcher in the Division of Molecular Cardiology, Department of Medicine at Texas A&M Health Science Center in Temple, Texas commented, “Our data revealed for the first time that TB4 selectively targets the Notch3-Col 3A-CTGF gene axis in preventing plant alkaloid-induced pulmonary hypertension and right ventricular hypertrophy. Our data revealed that inflammatory molecules which were triggered by the toxic plant alkaloid treatment were significantly reduced by TB4. Besides the anti-inflammatory effect, we demonstrated that TB4 also reversed the lung damage. Furthermore, the presence of significant fibrotic areas in the lungs of MCT-treated mice were observed in the untreated mice and significantly reduced in the TB4-treated mice. Together, our data underscore that treatment of TB4 attenuates inflammatory responses, reduces lung damage, and eventually restores the right ventricular pressure.”

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Allan L. Goldstein, Ph.D., RegeneRx’s chairman and chief scientific advisor added, “The study provides additional evidence that TB4 could be used as a vasculoprotective agent for the treatment of pulmonary hypertension-induced heart failure and confirms other independent studies showing the reduction of damage and improvement of function in both acute and sub-chronic cardiac models.”