Heart failure

Dominant form of heart failure caused by metabolic-immune interaction, review article suggests – ScienceDaily

The dominant form of heart failure worldwide appears to be caused by a strong two-way interaction between the body’s response to metabolic stress and the immune system, according to a review article by researchers and colleagues at UT Southwestern. The article, published in Nature Cardiovascular Researchpleads for more research on this root cause in order to develop truly effective treatments.

“Heart failure with preserved ejection fraction affects millions of people worldwide, but we currently have little to offer these patients because the underlying mechanisms are unknown. It is called the greatest unmet need for cardiovascular medicine,” the editor said. author Joseph Hill, MD, Ph.D., professor of internal medicine and molecular biology and chief of cardiology at UT Southwestern. “We now have insight into this condition that we didn’t even have five years ago, observations that could lead to viable clinical targets.”

Dr Hill explained that heart failure – the inability of the heart to pump blood efficiently – comes in two main types: heart failure with reduced ejection fraction (HFrEF), in which the amount of blood that leaves the heart with each beat decreases, and heart failure with preserved ejection fraction (HFpEF), in which the heart is unable to fill with blood to full capacity. While HFrEF has long been the most common form, HFpEF – which is associated with obesity, diabetes, and other components of the metabolic syndrome – has increased in prevalence in recent decades and has overtaken HFrEF as the most common form. more common.

Many treatments exist for different types of HFrEF, but these interventions have no discernible effect on HFpEF. Indeed, the two conditions are caused by different underlying mechanisms, said Dr. Hill, a subject his lab has studied for years. Although HFpEF can be improved through weight loss, weight loss is something many people struggle with, he added, which requires treatment.

In the review article, Hill and colleagues describe findings made in recent years that indicate metabolic and immune joint dysfunction are the root cause of HFpEF. For example, adipose tissue secretes inflammatory molecules that migrate to the heart, recruiting immune cells evident in cardiac biopsy specimens from individuals with HFpEF. At the same time, cardiac toxicity caused by the overconsumption of fatty acids for fuel in people with metabolic syndrome appears to stimulate an immune response, leading to a vicious cycle.

Crosstalk between fatty tissue, the immune system, and the heart appears to amplify both immune and metabolic stress, ultimately causing heart failure over time. But how this crosstalk happens, what effects it produces, and how to block them remains unclear, Dr. Hill said. Research in this new area of ​​immunometabolism sheds some light on these questions, but further research will be needed to produce effective interventions for patients with HFpEF, he added.

“Research from our lab and others raises possibilities for therapeutic targets that need to be investigated,” Dr. Hill said. “There is a reasonable chance that we could have therapies available for this incurable disease within the next decade.”

US news and world report ranks UT Southwestern as the #1 hospital in Texas for Cardiology and Cardiac Surgery and #11 in the nation.

Dr. Hill holds the James T. Willerson, MD, Chair of Excellence in Cardiovascular Diseases and the Frank M. Ryburn Jr. Chair in Cardiac Research.

Thomas G. Gillette, Ph.D., associate professor of internal medicine at UT Southwestern, contributed to the review article.

This work was supported by grants from DZHK (German Center for Cardiovascular Research); the Deutsche Forschungsgemeinschaft (German Research Foundation, SFB-1470-A02), IMI2-CARDIATEAM (no. 821508); Dutch Cardiovascular Research Initiative, Dutch Cardiovascular Alliance CVON2016-Early HFPEF, 2015-10, CVON She-PREDICTS, no. 2017-21; National Institutes of Health (HL144477, HL122309, HL126012, HL128215, HL120732, HL147933 and HL155765) and the American Heart Association (19TPA34910006).