Archive for November, 2011

ENVIRONMENT AND DIET LEAVE THEIR PRINTS ON THE HEART

Tuesday, November 29th, 2011

Cambridge, UK,
A University of Cambridge study, which set out to investigate DNA methylation in the human heart and the ‘missing link’ between our lifestyle and our health, has now mapped the link in detail across the entire human genome.

Dr. Roger Foo
Dr. Roger Foo
BHF Intermediate
Research Fellow
Cambridge University;
Hospitals NHS
Foundation Trust
Photo:cam.ac.uk

The new data collected greatly benefits a field that is still in its scientific infancy and is a significant leap ahead of where the researchers were, even 18 months ago. Researcher Roger Foo explains: “By going wider and scanning the genome in greater detail this time - we now have a clear picture of the ‘fingerprint’ of the missing link, where and how epigenetics in heart failure may be changed and the parts of the genome where diet or environment or other external factors may affect outcomes.”

The study originally began investigating the differences in DNA methylation found in the human heart. Researchers compared data from a small number of people with end stage cardiomyopathy who were undergoing heart transplantation, and the healthy hearts of age-matched victims of road traffic accidents.

DNA methylation leaves indicators, or “marks”, on the genome and there is evidence that these “marks” are strongly influenced by external factors such as the environment and diet. The researchers have found that this process is different in diseased and normal hearts. Linking all these things together suggest this may be the “missing link” between environmental factors and heart failure.

The findings deepen our understanding of the genetic changes that can lead to heart disease and how these can be influenced by our diet and our environment. The findings can potentially open new ways of identifying, managing and treating heart disease.

The DNA that makes up our genes is made up of four “bases” or nucleotides - cytosine, guanine, adenine and thymie, often abbreviated to C, G, A and T. DNA methylation is the addition of a methyl group (CH3) to cytosine.

When added to cytosine, the methyl group looks different and is recognised differently by proteins, altering how the gene is expressed i.e. turned on or off.

DNA methylation is a crucial part of normal development, allowing different cells to become different tissues despite having the same genes. As well as happening during development, DNA methylation continues throughout our lives in a response to environmental and dietary changes which can lead to disease.

As a result of the study, Foo likens DNA methylation to a fifth nucleotide: “We often think of DNA as being composed of four nucleotides. Now, we are beginning to think there is a fifth - the methylated C.”

Foo also alludes to what the future holds for the study: “…and more recent basic studies now show us that our genome has even got 6th, 7th and 8th nucleotides… in the form of further modifications of cytosines. These are hydroxy-methyl-Cytosine, formylCytosine and carboxylCytosine = hmC, fC and caC! These make up an amazing shift in the paradigm…”

As in most studies, as one question is resolved, another series of mysteries form in its place. The study shows that we are still on the frontier of Epigenetics and only just beginning to understand the link between the life we lead and the body we have.

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FETAL STEM CELLS FROM PLACENTA MAY HELP MATERNAL HEART RECOVER FROM INJURY

Monday, November 14th, 2011

Orlando, Florida

Hina Chaudhry
Hina Chaudhry
Cardiovascular Disease
MD, Harvard Medical School
Photo:mountsinai.org

Researchers from Mount Sinai School of Medicine have discovered the therapeutic benefit of fetal stem cells in helping the maternal heart recover after heart attack or other injury. The research, which marks a significant advancement in cardiac regenerative medicine, was presented today at the American Heart Association’s (AHA) Scientific Sessions 2011 in Orlando, Florida, and is also published in the current issue of Circulation Research, a journal of the AHA. In the first study of its kind, the Mount Sinai researchers found that fetal stem cells from the placenta migrate to the heart of the mother and home to the site where an injury, such as a heart attack, occurred. The stem cells then reprogram themselves as beating heart stem cells to aid in its repair. The scientists also mimicked this reprogramming in vitro, showing that the fetal cells became spontaneously beating heart cells in cell culture, which has broad reaching implications in treating heart disease.

Previous studies have documented a phenomenon in which half of women with a type of heart failure called peripartum cardiomyopathy saw their condition spontaneously recover in the months following pregnancy. Based on this evidence, the Mount Sinai team wanted to determine whether fetal stem cells played a role in maternal recovery.

They evaluated the hearts of pregnant female mice that underwent mid gestation heart injury and survived. Using green fluorescent protein in the fetuses to tag the fetal stem cells derived from the placenta, they found that the green fluorescent stem cells homed to the injured hearts of their mothers, grafted onto the damaged tissue, and differentiated into smooth muscle cells, blood vessel cells, or another type of heart cell called cardiomyocytes.

“Our research shows that fetal stem cells play an important role in inducing maternal cardiac repair,” said Hina Chaudhry, MD, Director of Cardiovascular Regenerative Medicine at Mount Sinai School of Medicine, and principal investigator of the study. “This is an exciting development that has far reaching therapeutic potential.”

With a broader understanding of the role of fetal stem cells, Dr. Chaudhry and her team then isolated the fetal cells that had grafted onto the maternal hearts and recreated the environment in vitro. They found that the cells spontaneously differentiated into cardiac cells in cell culture as well.

Until now, researchers have had limited success in discovering the regenerative potential of stem cells in heart disease. The use of bone marrow cells in cardiac regeneration has largely failed as well. Dr. Chaudhry’s research team has found that fetal cells may potentially be a viable therapeutic agent, both through in vivo and in vitro studies.

“Identifying an ideal stem cell type for cardiac regeneration has been a major challenge in heart disease research,” said Dr. Chaudhry. “Embryonic stem cells have shown potential but come with ethical concerns. We’ve shown that fetal stem cells derived from the placenta, which is discarded postpartum, have significant promise. This marks a significant step forward in cardiac regenerative medicine.”

These findings have implications beyond cardiovascular disease. The fetal stem cells traveled only to the injury site on the damaged heart, and not to other undamaged organs, meaning research on the benefit of these cells on organs damaged by other diseases would be beneficial. Importantly, a significant percentage of the fetal cells isolated from maternal hearts express a protein called Cdx2, which indicates that the cells may not have developed mature immune recognition molecules and therefore are unlikely to cause a negative immune response, which occurs in organ transplant.

“Our study shows the promise of these cells beyond just cardiovascular disease,” said Dr. Chaudhry. “Additionally, this breakthrough greatly underscores the importance of translational research. As a clinician who also has a basic science laboratory, I am in the unique position to assess the needs of my patients, evaluate how they respond to treatment and recover from illness, and bring that anecdotal knowledge to the experiments in my lab.”

>>>>>Read all the latest in our HeartVigor.com News Page.