Stay current with NHLBI Lab e-Notes, an e-newsletter highlighting research supported by the National Heart, Lung, and Blood Institute of the NIH.

In This Issue

• A Message from the NHLBI Director
  
• Fruit Flies Provide Clues to Heart Development
  
• Designer Rats Aid Search for Heart Disease Genes
  
• New Method Corrects Sickle-Cell Disease in Laboratory Model
  
• Hybrid Protein Protects Damaged Heart Cells
  
• Cellular Transformation Spurs Excess Mucus Production

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A Message from the NHLBI Director

Dear Colleague,

Welcome to the debut issue of NHLBI Lab e-Notes, an e-newsletter published by the National Heart, Lung, and Blood Institute highlighting some of the recent discoveries made by NHLBI-supported scientists in laboratories across the country.

The NHLBI has a long history of bringing to you the latest news on the diagnosis, prevention, and treatment of disease. We’re trying something different with NHLBI Lab e-Notes by focusing on basic science discoveries, the research behind the health and medicine headlines. In doing so, we hope to convey the excitement and promise of the entire spectrum of biomedical research—from bench to bedside. After all, it is the basic research advances that pave the way for breakthroughs in health and medicine.

NHLBI Lab e-Notes is designed to be a quick read, but we encourage you to follow the links to learn more. And, we aim to reach a broad audience—from the research and medical community to educators, students, and the public—so spread the word!

The NHLBI is always interested in receiving comments and suggestions from our readers, and research updates from NHLBI-supported scientists. Please, send an email to let us know what you think about NHLBI Lab e-Notes and what topics you would like to learn more about in future issues at: NHLBI_ResearchNews@nhlbi.nih.gov.

Regards,

Elizabeth G. Nabel, M.D. and Susan Shurin, M.D.
Director, NHLBI                      Deputy Director, NHLBI

Fruit Flies Provide Clues to Heart Development

Microscope image of the fly heart tube. Slit (green) aligns between heart cells (red). Image courtesy of Rolf Bodmer and Li Qian.

The tiny fruit fly Drosophila melanogaster is yielding big clues about early heart development and the causes of congenital heart defects.  According to Burnham Institute for Medicine researchers, two proteins, called Slit and Robo, are required for proper heart formation in flies and a malfunction of either alters the heart's structure, causing heart defects. As the heart develops, Slit and Robo accumulate in a very specific pattern within the heart tube—a primitive version of the heart that forms before its cells start beating. When the researchers altered the distribution of either protein, the heart tube assembled incorrectly. Scientists think the lessons learned could apply to people because genetically speaking, humans and Drosophila are strikingly similar.  In fact, humans also produce Slit and Robo, but more research is needed to link either protein to heart defects in children.

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PubMed Abstract

Designer Rats Aid Search for Heart Disease Genes

	Designer lab rats could help scientists pinpoint the genetic basis of cardiovascular disease.

New designer lab rats could help scientists pinpoint the genetic basis of cardiovascular disease, according to a report published in Nature Genetics . The strains bred by scientists from the Medical College of Wisconsin were specifically engineered to uncover genes that influence high blood pressure. Collaborators at The Institute for Genomic Research (TIGR) used DNA microarrays—or DNA chips—to see which genes were turned on or off in the designer rats compared with healthy and hypertensive strains. By studying the genetic profiles and physical characteristics of the different rats, the team identified candidate genes that may contribute to cardiovascular disease—including some not previously linked to the condition. Researchers can mine TREX, an online database of results from the study, free of charge at: http://pga.tigr.org .

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PubMed Abstract
Wisconsin PhysGen

New Method Corrects Sickle Cell Disease in Laboratory Model

Faulty hemoglobin transforms normally round red blood cells into a sickle-like shape, as shown above.

Using a combined approach of gene therapy and a technique called RNA interference, or RNAi, researchers have reversed sickle cell disease in cultured human cells. In sickle cell anemia patients, a gene mutation causes red blood cells to produce an abnormal version of the oxygen carrying protein hemoglobin. The faulty hemoglobin aggregates, transforming the normally round blood cells into narrow, crescent shaped ones with limited ability to flow through small blood vessels and deliver oxygen to tissues. Scientists at the Memorial Sloan-Kettering Cancer developed a new gene therapy method to introduce a healthy version of the hemoglobin gene into blood-producing stem cells isolated from sickle cell patients. They simultaneously shut down production of the abnormal hemoglobin using RNAi. In theory, the treated stem cells could be transplanted back into the patients they were obtained from, offering a superior alternative to the only cure available today—transplantation of compatible donor stem cells, a risky procedure available to very few patients.

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PubMed Abstract
Sickle Cell Disease Information

Hybrid Protein Protects Damaged Heart Cells

	Model of the three-dimensional structure of troponin (colored ribbons) bound to calcium molecules ( gray spheres). Illustration obtained from PDB database (troponin acquisition number 1LA0).

A fetal-like version of troponin, a protein that mediates the heart's response to calcium, may help improve function in damaged hearts according to researchers at the University of Michigan. Normally, heart muscle contracts when cellular calcium levels rise, and relaxes as calcium levels decline with each heart beat. But when acid accumulates due to decreased blood flow, such as after a heart attack, troponin's sensitivity to calcium is reduced. In turn, heart cells beat less efficiently-in adults at least. A fetal version of troponin found in very young hearts responds to calcium more effectively than the adult form under acidic conditions. This fetal protein is replaced during the late stages of heart development by an adult troponin that is better equipped to respond to hormones during stress and exercise. By changing a single amino acid in the adult troponin to the one found in the fetal version, researchers created a hybrid with the best of both worlds. The modified troponin dramatically improved cardiac function in damaged human heart cells, and mice subjected to conditions that mimic heart attack or heart failure. The researchers believe their work could someday lead to gene or cell-based therapies for heart failure patients.

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PubMed Abstract

Cellular Transformation Spurs Excess Mucus Production

Electron microscope image of hair-like cilia surrounding rounded goblet cells in the airway. Credit: © Dr. Kessel & Dr. Kardon, Visuals Unlimited.

Researchers have discovered that a transformation of some lung cells from one type to another leads to a serious complication of asthma and other chronic lung diseases—excess mucus production. While a certain amount of the sticky stuff is required to trap inhaled particles, bacteria, and other foreign invaders, extra mucus can clog airways causing coughing and shortness of breath. Researchers at the Washington University School of Medicine observed that the lungs of mice with an experimentally induced asthma-like condition make excessive numbers of mucus producing cells—called goblet cells. Further experiments showed that two cellular mechanisms contribute to the goblet cell build-up. The first mechanism prolongs the lives of specialized cells that sweep debris out of airways using tiny “hairs” called cilia. The second helps transform the long-lived ciliated cells into goblet cells. The team successfully blocked both mechanisms using two different drugs, opening up new possibilities for the treatment of excess mucus production in chronic lung disease patients.

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PubMed Abstract