Human Cardiotrophin 1 Protein Improves Heart Function in Rats with PAH, Study Shows

Human cardiotrophin 1 protein (hCT1) stimulates heart muscle growth in rats with induced right heart failure (RHF) due to severe pulmonary arterial hypertension, leading to improved heart function, a new study shows. The results suggest that hCT1 could be beneficial for patients with an intractable form of heart failure.

The study, “Cardiotrophin 1 stimulates beneficial myogenic and vascular remodeling of the heart,” was published online in the journal Cell Research this month.

Pulmonary arterial hypertension (PAH) leads to RHF, which is the inability of the right ventricle of the heart to pump blood to the lungs, where oxygen is taken up.

There are two kinds of cardiac hypertrophy: physiologic, which is beneficial, and pathologic, which leads to heart failure. The study found that hCT1 caused physiologic cardiac hypertrophy, or heart muscle growth, in laboratory rats with PAH.

“Physiologic cardiac hypertrophy is a form of beneficial remodeling, characterized by a modest increase in heart mass with improved contractile function that is reversible,” the researchers noted. Physiologic cardiac hypertrophy improves heart performance in both healthy and diseased individuals.

Early treatment of PAH rats with hCT1 protein, before RHF had developed, prevented RHF from occurring. The researchers suggest that hCT1 improved heart function by inducing remodeling events specifically in the heart.

After PAH and RHF were induced in laboratory rats, they were then continuously pumped with hCT1 protein for two weeks. Following that period, cardiac output improved and new small blood vessels grew in the hCT1-treated rats’ hearts, which was not seen in control rats. Overall, hCT1 treatment reversed RHF in the rats.

The protein caused heart muscle cells to grow in a healthy way and induced the production of new blood vessels, increasing the heart’s ability to pump blood.

“The myocardial and vascular remodeling capacity of CT1 implies that it may be effective in combating myopathies and ischemic heart disease in general,” the researchers concluded. “Here, we demonstrate that human CT1 protein (hCT1) engages a fully reversible form of myocardial growth, and that hCT1 attenuates the ongoing pathology and loss-of-function in an aggressive and unremitting model of right heart failure (RHF).”