More than 6.7 million people in the U.S. are living with heart failure, a condition where the heart cannot pump enough blood and oxygen to support the body.
That number is expected to reach 8.5 million by 2030. A specific type of heart failure, called HFpEF (Heart Failure with preserved Ejection Fraction), is becoming more common, but remains difficult to treat.
In a new study published in the journal *JACC: Basic to Translational Science*, researchers from Temple University and Cedars-Sinai used a systems-biology approach to better understand this challenging condition. Their focus was to uncover how changes in metabolism and mitochondrial function contribute to HFpEF.
Unlike another type of heart failure (HFrEF), which responds better to drugs, HFpEF lacks effective treatment options. That’s partly because scientists still don’t fully understand what causes it. The National Heart, Lung and Blood Institute has identified HFpEF as the biggest unmet need in cardiovascular medicine today.
“HFpEF was not even well-recognized until about 10 years ago,” said study leader Professor John Elrod. “We still don’t fully understand what’s driving the disease. That’s why we took a deep dive into how cells in the heart change at a molecular level.”
Elrod’s team analyzed heart cells using high-tech methods like RNA sequencing and electron microscopy. They looked at changes in gene activity and closely studied mitochondria, the energy powerhouses inside cells.
These mitochondria were found to change shape and structure during HFpEF progression and had trouble functioning properly.
The researchers found that adding obesity to existing health issues like high blood pressure and blood vessel problems caused more severe HFpEF. The team created a model showing how heart cell function changes over time, linking changes in genes to changes in how the cells produce energy.
One major discovery was how the mitochondria become “remodeled” and lose their ability to make energy efficiently. The team also discovered that mitochondria no longer interact well with other cell structures, which makes the disease worse.
This work could help identify new targets for future drugs. The researchers aim to find out if changing how certain genes work or using medications to support mitochondrial function might stop or slow down the disease.
“This is a discovery-based study, and those are the most exciting because we go in without assumptions,” said Elrod. “We’re just looking for the hidden signs, the key pieces of the puzzle. Once we find them, we can test new ways to treat this disease.”
The team hopes their findings will lead to the development of new treatments for HFpEF patients—treatments that address the underlying problems with metabolism and energy production at the cellular level.
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The study is published in JACC: Basic to Translational Science.
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