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'Two-hit' model helps solve greatest unmet need in cardiology


In a new study, the researchers have found that combining a high-fat diet with a drug that raises blood pressure gave them a 'two-hit' model, like a one-two punch to the

The study published in the journal Nature, reveals that nearly half of the hospital admissions for are caused by a type of the with no treatment options.

"There are two types of One is called HFrEF, for which we have a number of therapies, including medications, devices, and transplants. The other - HFpEF - has zero options," said Chief of the and Professor of Internal and Molecular Biology Dr

"HFpEF is the single greatest unmet need in cardiology. Finding a new way to examine it represents a significant advance, as it provides a necessary to develop and test therapies that could save lives worldwide," said Dr Hill, who holds the James T. Willerson, M.D. Distinguished in and the Frank M. Ryburn, Jr. in Heart Research.

The Centers for Control and Prevention estimates that 5.7 million people have in the U.S.

Heart failure with preserved ejection fraction (HFpEF) is a for which there are no effective clinical therapies. The heart muscle becomes too stiff to pump blood efficiently. Most HFpEF patients are obese, have diabetes, and have

Heart failure with reduced ejection fraction (HFrEF) functions differently. In HFrEF, also known as systolic HF, the heart muscle is not able to contract adequately and, therefore, expels less oxygen-rich blood into the body. Previous heart failure models of HFpEF focused on raising the levels of an enzyme called NO, or nitric oxide synthase.

However, in HFpEF, there is actually too much of the NO enzyme. A strike on this target - with a medical inhibitor, for example - would solve the problem. According to Dr Hill, there are already FDA-approved drugs that inhibit this NO-synthesize enzyme, which could facilitate developing new treatments rapidly.

The two-hit model

Dr Hill's team looked at current, ineffective models of HFpEF and concluded that none of them correctly mirrors the realities they see clinically in human patients. They found that combining a high-fat diet with a drug that raises blood pressure gave them a "two-hit" model, like a one-two punch to the disease.

Next, the team examined the results of their at the cellular level and compared them with human cells. They found that they had replicated the human condition, thereby providing scientists with an accurate biological picture that can greatly advance the development of new treatments.

"A recognized research gap in the HFpEF field is the lack of relevant experimental models that adequately represent the progression of this This study is an example of how advances in HFpEF models can lead to a better understanding of the disease pathophysiology and new ideas for therapeutic strategies," said Dr Bishow Adhikari, a for the study.

Millions of people worldwide have both and The research team believed that these two conditions would lead to HFpEF - a hypothesis they confirmed by duplicating the disease conditions and examining changes at the molecular level.

"Heart failure is one of only two forms of that is increasing. It's exploding around the world. We dance around the edges of it, treating patients' diabetes, blood pressure, and other conditions. With this model, we'll be able to get to the underlying cause so we can get to the root of the problem," Dr Hill said.

The researchers are currently taking steps toward moving into human clinical trials based on findings in their preclinical two-hit With time, they expect that all heart failure patients will have treatment options.

(This story has not been edited by Business Standard staff and is auto-generated from a syndicated feed.)

First Published: Fri, April 12 2019. 12:58 IST