New insights into the development of heart disease therapeutics

June 1, 2018, University of Helsinki
Researchers Daria Blokhina, Esko Kankuri, Päivi Lakkisto, Maciej Lalowski, Rabah Soliymani, and Eero Mervaala. Credit: University of Helsinki

The heart of a neonatal mouse is capable of self-repair after tissue damage. However, this ability disappears during the first week of life. Researchers at the University of Helsinki investigate the molecular mechanisms underlying myocardial regenerative ability. Advantages within the field could be of benefit, for example, in the development of novel treatments for patients to regain heart function after myocardial infarction.

During the first days of life, the heart of a newborn mouse adapts to entirely new physiological conditions, larger volume loads and an increased energy demand. As a result, fundamental changes occur in the heart. Studies have shown that the heart of neonate mouse retains its ability to effectively repair . This ability of the cardiac muscle to regenerate, however, gradually disappears during the first week of life.

One major problem in the treatment of heart disease is the inability of adult myocardial cells to regenerate. Thus, tissue damaged by, for example, is not revived. New approaches for developing novel treatments are being sought to help patients regain after myocardial infarction.

A research collaboration at Meilahti campus investigates the underlying myocardial regenerative ability. Research groups from the Medical Faculty at the University of Helsinki, the Institute of Molecular Medicine Finland (FIMM) and the Minerva Foundation Institute for Medical Research have recently published an analysis that combined three different systems-level methods on mechanisms associated with the loss of regenerative ability of the heart soon after birth.

The researchers used a large scale analytical platforms approach combining RNA sequencing, quantitative proteomics and metabolomics as well as bioinformatics to characterize the events initiated in the hearts of newborn mice during the first week after birth.

"We used a combination of different systems-level techniques and utilized the tools of transcriptomics, proteomics, metabolomics and bioinformatics. Co-operating with the top experts from different groups at the Meilahti campus, we were able to get a very comprehensive view of how the heart's metabolism is re-programmed within the first postnatal week," says Docent Esko Kankuri.

"Utilizing a 'multiomics' approach, we identified several cellular message pathways and processes that affect the re-programming of heart metabolism after birth. We discovered core molecular level events behind the regenerative capacity of the heart. Through our research, 1 937 proteins, 612 metabolites and 2 586 gene loci were associated with these processes," Kankuri adds.

Fructose-induced glycolysis was a key factor for myocardial regenerative ability, an activity associated with an increased proliferation of cells during the first days after birth.

"These results also help us to understand the mechanisms of the human disease and what molecular factors affect myocardial regeneration. Understanding these mechanisms can open up possibilities for developing new types of treatments," says Docent Maciej Lalowski.

Explore further: Macrophage population activates repair in murine heart attack model

More information: Maciej M. Lalowski et al. Characterizing the Key Metabolic Pathways of the Neonatal Mouse Heart Using a Quantitative Combinatorial Omics Approach, Frontiers in Physiology (2018). DOI: 10.3389/fphys.2018.00365

Related Stories

Macrophage population activates repair in murine heart attack model

May 3, 2016
Following a heart attack, successful repair of damaged tissue can prevent cardiac rupture and other adverse outcomes. The ability to repair myocardial tissue depends on the activation of fibroblasts, which stimulate the formation ...

Mammalian heart regenerative capacity depends on severity of injury

January 22, 2015
A new study by researchers at Children's Hospital Los Angeles has shown that neonatal mouse hearts have varying regenerative capacities depending upon the severity of injury. Using cryoinjury - damaging the heart through ...

Scientists describe the mechanism of heart regeneration in the zebrafish

February 12, 2018
Some animals, including the zebrafish, have a high capacity to regenerate tissues, allowing them to recovery fully after cardiac injury. During this process, the heart muscle cells divide to replace the damaged tissue. However, ...

Blood cancer gene could be key to preventing heart failure

October 16, 2017
A new study, published today in Circulation, shows that the gene Runx1 increases in damaged heart muscle after a heart attack. An international collaboration led by researchers from the University of Glasgow, found that mice ...

A pathway controlling inflammatory responses aids recovery after heart attack

February 6, 2017
After a heart attack, or myocardial infarction, a patient's long-term prognosis depends on the ability of the heart tissue to heal and remodel. Immune system activation and inflammatory responses that occur in the aftermath ...

Research pinpoints key gene for regenerating cells after heart attack

December 20, 2012
UT Southwestern Medical Center researchers have pinpointed a molecular mechanism needed to unleash the heart's ability to regenerate, a critical step toward developing eventual therapies for damage suffered following a heart ...

Recommended for you

New cellular pathway helps explain how inflammation leads to artery disease

June 21, 2018
Investigators have identified a new cellular pathway that may help explain how arterial inflammation develops into atherosclerosis—deposits of cholesterol, fats and other substances that create plaque, clog arteries and ...

'Smart stent' detects narrowing of arteries

June 19, 2018
For every three individuals who have had a stent implanted to keep clogged arteries open and prevent a heart attack, at least one will experience restenosis—the renewed narrowing of the artery due to plaque buildup or scarring—which ...

Marriage may protect against heart disease / stroke and associated risk of death

June 18, 2018
Marriage may protect against the development of heart disease/stroke as well as influencing who is more likely to die of it, suggests a pooled analysis of the available data, published online in the journal Heart.

Deaths from cardiac arrest are misclassified, overestimated

June 18, 2018
Forty percent of deaths attributed to cardiac arrest are not sudden or unexpected, and nearly half of the remainder are not arrhythmic—the only situation in which CPR and defibrillators are effective—according to an analysis ...

Tick-borne meat sensitivity linked to heart disease

June 15, 2018
University of Virginia School of Medicine researchers have linked sensitivity to an allergen in red meat—a sensitivity spread by tick bites—with a buildup of fatty plaque in the arteries of the heart. This buildup may ...

The molecules that energize babies' hearts

June 14, 2018
A metabolic process that provides heart muscle with energy fails to mature in newborns with thickened heart walls, according to a Japan–Canada research team.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.