Researchers in Australia have developed a strategy they hope can help repair damaged hearts following a heart attack.
Within about three days of a heart attack, heart cells can die due to lack of oxygen and scar tissue begins to form, which is more stiff and less contractile than the muscle it has replaced. The adult heart cannot produce new healthy tissue after this response and the scarring remains. The heart wall ultimately thickens and stiffens, and this increases the stress on the heart and heightens the risk of future heart failure.
The new strategy could potentially help millions of patients to live normal lives after a heart attack. While all patients receive drug treatment after a heart attack, the prognosis for heart failure remains poor, and almost half of patients die within five years.
The team from the University of Sydney have injected a soluble subunit of elastin – tropoelastin – into the outside wall of the heart in rats that had an induced heart attack (Circulation Res., doi: 10.1161/CIRCRESAHA.122.321123). Elastin is a stretchy protein that plays a role in the elasticity and tensile characteristics of tissue.
‘After heart attacks, the scarred heart becomes deleteriously rigid and tropoelastin is known to give elastic properties to skin,’ says James Chong, a heart specialist at Sydney University. ‘We hypothesised that if we could get the injured heart to incorporate and produce more tropoelastin and elastin then this would improve heart function.’
An echocardiograph evaluation showed that the tropoelastin injection significantly improved the heart function; tissue assessment subsequently showed a reduced scar in treated animals, as well as more elastin in the scar. ‘We think tropoelastin is incorporated into resident cardiac fibroblasts and this helps decrease the rigidity of the scarred heart,’ notes Chong. The mechanism is not fully understood. However, the researchers were surprised to discover some elastin is produced after a heart attack. A key question, adds Chong, is why the heart does not produce more elastin after damage, like skin does.
‘The extent of improvement of cardiac function is somewhat surprising, given that the treatment mainly targets the mechanical properties of the scar,’ comments pharmacologist Virpi Talman at the University of Helsinki, Finland. ‘A similar improvement in heart function in humans would probably allow millions of ischaemic heart disease patients to live normal lives after a myocardial infarction.’
This was a proof of concept study, however. A human heart is much larger, beats faster and is under higher pressure. Also, the rodent study was over a period of just four weeks.
‘Further studies are required to determine the long-term efficacy and safety of the treatment as well as the mechanisms by which the treatment reduced the scar size,’ notes Talman. ‘Studies in larger animals, such as pigs or non-human primates, whose hearts resemble human hearts more closely, are needed.’
One unknown is what happens if an injured heart becomes too elastic. ‘Potentially the newly produced elastic may have unforeseen electrophysiological effects that may adversely impact the human heart after repair,’ Chong notes.
‘Interestingly, tropoelastin is known to be expressed quite strongly in the developing embryo but in adults this protein is generally only produced in response to some injury settings,’ adds Chong. ‘To our knowledge, there has been no research prior to our study on tropoelastin and heart repair.’