Tug of war between Parkinson’s protein and growth factors

A “tug of war” situation exists between Parkinson's provocateur protein alpha-synuclein and the growth factor Read more

From stinging to soothing: fire ant venom may lead to skin treatments

Compounds derived from fire ant venom can reduce skin thickening and inflammation in a mouse model of psoriasis, Emory and Case Western scientists have Read more

Troublemaker cells predict immune rejection after kidney transplant

Evidence is accumulating that the presence of certain "troublemaker" memory T cells can predict the likelihood of belatacept-resistant immune Read more

Division of Cardiology

Direct reprogramming into endothelial cells

Direct reprogramming has become a trend in the regenerative medicine field. It means taking readily available cells, such as skin cells or blood cells, and converting them into cells that researchers want for therapeutic purposes, skipping the stem cell stage.

In a way, this approach follows in Nobel Prize winner Shinya Yamanaka’s footsteps, but it also tunnels under the mountain he climbed. Direct reprogramming has been achieved for target cell types such as neurons and insulin-producing beta cells.

Young-sup Yoon, MD, PhD

In Circulation Research, Emory stem cell biologist Young-sup Yoon, MD, PhD and colleagues recently reported converting human skin fibroblast cells into endothelial cells, which line and maintain the health of blood vessels.

Once reprogrammed, a patient’s own cells could potentially be used to treat conditions such as peripheral artery disease, or to form vascular grafts. Exactly how reprogrammed cells should be deployed clinically still needs to be worked out.

In cardiovascular disease, many clinical trials have been performed using bone marrow cells that were not reprogrammed. Emory readers may be familiar with studies conducted by Arshed Quyyumi, MD and colleagues, in which treatment was delivered after patients’ heart attacks. In those studies, sorted progenitor cells, some of which could become endothelial cells, were introduced into the heart. To provide the observed effects, the introduced cells were more likely supplying supportive growth factors.

In contrast, Yoon’s team is able to produce cells that already have endothelial character hammered into them. The authors have applied for a patent. The co-first authors were instructor Sang-Ho Lee, PhD and Changwon Park, PhD, assistant professor of pediatrics. Read more

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Oxidative stress ain’t about free radicals, it’s about sulfur

This recent paper in Circulation, from Arshed Quyyumi and colleagues at the Emory Clinical Cardiovascular Research Institute, can be seen as a culmination of, even vindication for,  Dean Jones’ ideas about redox biology.

Let’s back up a bit. Fruit juices, herbal teas, yogurts, even cookies are advertised as containing antioxidants, which could potentially fight aging. This goes back to Denham Harman and the free radical theory of aging. [I attempted to explain this several years ago in Emory Medicine.]

We now know that free radicals, in the form of reactive oxygen species, can sometimes be good, even essential for life. So antioxidants that soak up free radicals to relieve you of oxidative stress: that doesn’t seem to work.

Dean Jones, who is director of Emory’s Clinical Biomarkers laboratory, has been an advocate for a different way of looking at oxidative stress. That is, instead of seeing cells as big bags of redox-sensitive chemicals, look at cellular compartments. Look at particular antioxidant proteins and sulfur-containing antioxidant molecules such as glutathione and cysteine.

That’s what the Circulation paper does. Mining the Emory Cardiovascular Biobank, Quyyumi’s team shows that patients with coronary artery disease have a risk of mortality that is connected to the ratio of glutathione to cystine (the oxidized form of the amino acid cysteine).

How this ratio might fit in with other biomarkers of cardiovascular risk (such as CRP, suPAR, PCSK9, more complicated combinations and gene expression profiles, even more links here) and be implemented clinically are still unfolding.

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A spoonful of sugar helps infection detection

Congratulations to Kiyoko Takemiya, a postdoctoral fellow in Emory’s Division of Cardiology, working with W. Robert Taylor. At the recent American College of Cardiology meeting in Washington DC, she won first place in the competition for an ACC Foundation/ Herman K. Gold Young Investigators Award in Molecular and Cellular Cardiology.

The title of her research presentation was: A Novel Imaging Probe for the Detection of Subclinical Bacterial Infections Involving Cardiac Devices.

Takemiya, Taylor, and their colleagues (including Mark Goodman and Niren Murthy, formerly at Georgia Tech and now at UC Berkeley) developed a fluorescent probe that allows the detection of small levels of bacteria on cardiac devices. The probe was tested in rats, some of which had relatively mild local S. aureus infections. The fluorescent probe (PET is also under investigation) makes use of the properties of maltohexaose, a sugar that is taken up by bacteria but not mammalian cells.

Infection rates for implantable cardiac devices such as pacemakers have been rising, according to a 2012 paper in NEJM.

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Possible diabetes drug/stent interaction

Diabetes and heart disease often intersect. Emory cardiologist Aloke Finn and his colleagues recently had two papers in the Journal of the American College of Cardiology and in Atherosclerosis describing a possible interaction between the widely used diabetes drug metformin and drug-eluting stents, which are used to to treat coronary artery disease. Anwer Habib, MD is the first author of both papers.

The stent props the once-blocked artery open while the drugs in the stents are supposed to prevent the artery from becoming blocked again. The drugs — usually mTOR inhibitors such as http://www.magliettedacalcioit.com everolimus or the newer zotarolimus — slow down cell growth, but this cuts both ways. The drugs slow down the recovery of the lining of the blood vessel and this may contribute to blood clot formation after stent placement.

In cultured human cells and in rabbits with implanted stents, Finn and colleagues showed that metformin augmented the effect of mTOR inhibitors on regrowth of the blood vessel lining. (However — the authors acknowledge that their animal model was not diabetic or atherosclerotic.)

The findings could mean that people taking metformin would need to take medications to prevent blood clotting medications for a longer time after stent placement. The authors say that clinical studies following patients who receive drug-eluting stents should look at metformin’s effects on blood clotting events. A study examining drug eluting stents in diabetic patients is in the works at Emory.

 

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