Heart disease insights point to potential therapy

Scientists have taken a step towards understanding a common heart condition affecting dogs and people.

Studies of cells from dogs with moderate myxomatous mitral valve degeneration – a form of heart disease – have revealed key biological factors influencing the condition, and the processes involved. 

Their discovery presents a path towards identifying drugs to manage the condition in canines and in people, whose heart valve anatomy is similar.

Researchers from the Roslin Institute studied cells in tissue from dogs affected by mitral valve degeneration, and compared these with tissue from healthy dogs, to better understand the disease in detail.

Their studies, which focused on key proteins known to be linked with disease, found that a process known as autophagy, a form of cellular housekeeping which removes damaged or unwanted material, is central to the disease.

The team discovered that autophagy is impaired in the ageing cells that are a feature of the disease.

Their research shows that autophagy regulates cell ageing, a feature of the disease, by degradation of two key proteins. The team also discovered the process by which this occurs and introduced a new term, senophagy, to describe this specific type of autophagy.

Previous studies had suggested a link between autophagy and activity in these proteins, but the latest study is the first to demonstrate the connection and the process underpinning it.

The team also discovered a biological pathway that could be targeted by drugs to prevent or manage the condition, and identified an existing class of drugs, known as MTOR inhibitors, that could potentially be used to regulate autophagy.

Scientists suggest their insights may also be relevant to neurodegenerative diseases such as dementia, because the diseases share characteristics such as impaired autophagy, the ageing of cells, and aggregation of cellular waste materials.

The team’s approach of studying the condition in dogs confers benefits compared with traditional scientific studies in mice, because heart valves in dogs are more similar to those of humans compared with mice. 

In addition, dogs exhibit similar disease traits compared to humans, allowing studies of the condition during onset and development by studying affected dogs. The availability of affected tissues from humans, by contrast, is typically limited to late-stage disease.

The study was published in Autophagy.