DNA from heart's own cells plays role in heart failure by mistakenly activating immune system

DNA from the heart's own cells plays a role in heart failure by mistakenly activating the body's immune system, according to a study by British and Japanese researchers, co-funded by the British Heart Foundation (BHF). Scientists from King's College London and Osaka University Medical School in Japan showed that during heart failure – a debilitating condition affecting 750,000 people in the UK – this 'rogue DNA' can kick start the body's natural response to infection, contributing to the process of heart failure.

During immune cells invade the heart, a process called inflammation. The process makes heart muscle less efficient, reducing its ability to pump blood around the body. Inflammation is usually only activated when the body is facing a threat, such as an infection by a bacteria or virus.

The study, to be published today in the journal Nature, shows in mice that inflammation in the heart can be caused by the body's own DNA. The DNA escapes when a natural process to break down damaged cell components, called autophagy, becomes less efficient. Autophagy can stop working correctly when cells are under stress, such as during heart failure.

The problem DNA comes from energy-generating structures in heart cells, called mitochondria. Mitochondrial DNA triggers inflammation because it resembles DNA from bacteria, triggering a receptor in immune cells called Toll-like Receptor 9 (TLR9).

Mitochondria fascinate scientists because they seem to have evolved from bacteria more than 1.5 billion years ago, when primitive forms of life recruited bacteria to help them produce their energy. Although this pact with bacteria is one of evolution's success stories, this study shows that the human immune system still recognises the bacterial fingerprint in mitochondrial DNA, triggering a response from the immune system.

Professor Kinya Otsu, recently announced as BHF Professor of Cardiology at King's College London, who led the study, said: 'When mitochondria are damaged by stress, such as during heart failure, they become a problem because their DNA still retains an ancient bacterial fingerprint that mobilises the body's defences.

'We previously showed that damaged mitochondria build-up during heart failure, when the natural processes of cell breakdown become less effective. Now we've shown that the DNA fingerprint that we retain in our mitochondria causes our own immune system to turn against us.'

Dr Shannon Amoils, Research Advisor at the BHF, said: 'This intriguing discovery is an important breakthrough in our understanding of why, during heart failure, the becomes activated without the presence of any obvious external threat. This inflammation in the heart plays an important role in the disease process.

'Heart are packed with mitochondria, which provide the power the heart needs to pump blood around the body, and this study shows that, during heart failure, from these mitochondria at least partly causes the problem. This research points towards new avenues of exploration that could hopefully lead to treatments for heart failure in the future.'

Professor Kinya Otsu was recently awarded more than £3 million by the BHF to carry out his pioneering work.

More information: Takafumi Oka et al (2012). Nature. Mitochondrial DNA That Escapes from Autophagy Causes Inflammation and Heart Failure. doi:10.1038/nature10992

Related Stories

Scientists identify genetic link for a 'heavy heart'

Oct 05, 2011

(Medical Xpress) -- An international research team led by Imperial College London has for the first time pinpointed a single gene associated with one of the leading causes of heart thickening and failure.

Heart failure's effects in cells can be reversed with a rest

Apr 02, 2012

Structural changes in heart muscle cells after heart failure can be reversed by allowing the heart to rest, according to research at Imperial College London. Findings from a study in rats published today in the European Jo ...

New heart failure device is tested

Oct 17, 2006

Physicians at 50 U.S. medical facilities are taking part in a multinational clinical trial of a device designed to help heart failure victims.

Recommended for you

Researchers discover neuroprotective role of immune cell

16 hours ago

A type of immune cell widely believed to exacerbate chronic adult brain diseases, such as Alzheimer's disease and multiple sclerosis (MS), can actually protect the brain from traumatic brain injury (TBI) and may slow the ...

User comments