The big news from the American College of Cardiology meeting today is about PCSK9 inhibitors, which were known to be effective at lowering LDL cholesterol, and how much they really prevent heart attacks and save lives.
Lab Land went looking off the beaten path for individual stories of Emory cardiologists saving lives and was pleased to find several. We highlight here three remarkable case reports that are being presented at the ACC meeting. We look forward to learning more about these cases.
Refractory electrical storm
Electrical storm is life threatening and refers to a recurrent arrhythmia. The arrhythmia did not respond to drug treatment, so anesthesiologists were brought in to perform left stellate ganglion block, an injection of medication into a nerve bundle in the neck, allowing diagnosis and further treatment. It turns out the arrhythmia was caused by sarcoidosis, a rare intrusion of immune cells into the heart. [Saturday morning: Michael Lloyd, Boris Spektor]
Hormone-producing tumor + cardiomyopathy
A 30-year old woman came to doctors with drastically impaired heart function, although she did not have a blockage of her coronary arteries or signs of damage to the heart muscle. Doctors discovered a tumor near her spine that was producing heart-distorting hormones such as epinephrine. She underwent surgery to remove the tumor. [Saturday afternoon: Stamatios Lerakis]
Giving birth unveils birth defects
Ten days after giving birth, a woman came to a hospital with chest pain. Upon cardiac catheterization, a rearrangement of her coronary arteries was discovered. It appears that the congenital defect had gone undetected until the stress of giving birth. Under medical treatment, she is asymptomatic, but she will need future monitoring and possibly a procedure to correct the artery problems. [Sunday morning: Camden Hebson]
Thanks to biomedical engineer Mike Davis for writing an explanation of “Exosomes: what do we love so much about them?” for Circulation Research, a companion to his lab’s November 2016 publication analyzing exosomes secreted by human cardiac progenitor cells.
We can think of exosomes as tiny packages that cells send each other. They’re secreted bubbles containing proteins and regulatory RNAs. Thus, they may be a way to harvest the regenerative capacity of pediatric heart tissue without delivering the cells themselves.
Davis’ lab studied cardiac tissue derived from children of different ages undergoing surgery for congenital heart defects. The scientists isolated exosomes from the cardiac progenitor cells, and tested their regenerative activity in rats with injured hearts.
They found that exosomes derived from older children’s cells were only reparative if they were subjected to hypoxic conditions (lack of oxygen), while exosomes from newborns’ cells improved rats’ cardiac function with or without hypoxia. Read more
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
On Friday, researchers from Emory Clinical Cardiovascular Research Institute demonstrated a test for how much blood vessels adjust to changes in blood flow. This test is known as “flow-mediated dilation” or FMD. A blood pressure measurement cuff is tightened on the arm for five minutes, restricting blood flow.
ECCRI investigator Salman Sher, MD demonstrates flow-mediated dilation
When the cuff is released, blood flow increases, but how much the arm’s main artery expands depends on the endothelium – the lining of the artery — and its ability to respond to nitric oxide, which is induced by the increased flow. Researchers monitor the artery’s expansion by ultrasound.
ECCRI co-director Arshed Quyyumi and his colleagues at Emory have extensive experience using the FMD test. Impaired endothelial function is an early stage in the process of atherosclerosis.
The FMD test is relatively non-invasive, in that no catheter probe is necessary. However, practitioners need practice and careful study design to ensure accuracy, ECCRI investigator Salman Sher explained. Posture, time of day and whether the patient has eaten can all affect the results.
Lab Land asked Sher (seated in the photo) whether the effect was similar to the common experience of sleeping on an arm and having it turn numb, followed by “pins and needles” when the pressure is relieved. This feeling actually comes from nerve compression. Read more
Clinical research presentations at 2016 American Heart Association Scientific Sessions: telomeres + circulating progenitor cells, food deserts, and troponin as risk marker for atrial fibrillation.
Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes Nov. 13, 4:45 pm, Room 346-347
Aging, in general, depletes our bodies’ regenerative capacities. Arshed Quyyumi, MD and colleagues at Emory Clinical Cardiovascular Research Institute have shown how circulating progenitor cells or CPCs, which regenerate blood vessels and correlate with outcomes in cardiovascular disease, are a finite resource.
Working with Quyyumi, research fellow Muhammad Hammadah, MD is presenting data on how telomere length interacts with the levels of CPCs, in a study of mental stress ischemia in 566 patients with stable coronary artery disease. Telomeres tend to shorten with ageing and cellular stress, and their length has been a widely studied biomarker.
Hammadah concludes that low leukocyte telomere length is associated with decreased regenerative capacity, independently of age and cardiovascular risk factors. However, telomere length and CPC levels are independent and additive predictors of adverse cardiovascular outcomes (such as death, heart attack, stroke, or hospitalization for heart failure), he finds. Hammadah is a finalist for the Elizabeth Barrett-Connor Research Award for Young Investigators in Training. Read more
Basic research presentations at 2016 American Heart Association Scientific Sessions: cell therapy for heart attack (mesenchymal stem cells) in animal models and role of CD73, gradual release drug for atrial fibrillation, how particles from stored blood affects blood vessels.
Mesenchymal Stem Cells Require CD73 Activity to Reduce Leukocyte Associated Inflammation Following Myocardial Ischemia-Reperfusion Injury
Nov.13, 1:30 pm, Science and Technology Hall- Basic Science Theater
Cell therapy, using the patient’s own cells to reduce damage to the heart after a heart attack, has been a hot topic. Mesenchymal stem cells are derived from the bone marrow and can’t replace heart muscle. But they do exert anti-inflammatory and anti-oxidative effects, Eric Shin, MD, Rebecca Levit, MD and colleagues show in a rat model of heart attack.
The researchers use the gel material alginate to encapsulate the cells, in a way previously described by Levit. They say this is the first study to demonstrate that mesenchymal stem cells reduce reactive oxygen species production in the heart. and that the molecule CD73, which degrades ATP/ADP into adenosine, is needed for the anti-inflammatory effect. CD73 is also a cancer immunotherapy target. Read more
For Halloween, Lab Land welcomes a guest post from Neuroscience graduate student Amielle Moreno, former editor of the Central Sulcus newsletter.
While recent studies have found evidence for the healing properties of blood from younger individuals, the fascination with “young blood” has been a part of the human condition for centuries.
In ancient Greece, Hippocrates introduced the concept that our health and temperament was controlled by the four humors, proposing that blood was the one responsible for courage, playfulness as well as hope. From the 16th century story of Countess Elizabeth Báthory de Ecsed of Hungary, the idea of “blood baths” acquired decidedly more sinister connotations.
The “Blood Countess” holds the Guinness World Record as the most prolific female murderer. With 80 confirmed kills, Báthory might have lured up to 650 peasant girls to her castle with the promise of work as maidservants or courtly training. Instead of etiquette lessons, they were burned, beaten, frozen or starved for the Countess’ sadistic pleasure. Folk stories told how she would bathe in the blood of virgins to preserve her youth and beauty.
Portrait if Elizabeth Bathory, via Wikimedia
Humors remained a staple of traditional western medicine until the 1800s when medical research and our modern concept of medicine emerged. In this more enlightened age, people started sewing animals together to see what would happen.
In the mid-1800s, a French zoologist named Paul Bert first experimented with the creation of parabionts: the surgical joining of two animals, usually two rodents of the same species, in order to study the effect of one’s blood on the other. Read more