Miller School Researchers Present Findings At AHA Scientific Sessions

Main Category: Heart Disease
Also Included In: Cardiovascular / Cardiology
Article Date: 20 Nov 2009 - 1:00 PDT

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A multidisciplinary team of clinical and basic science researchers in the Vascular Biology Institute at the University of Miami Miller School of Medicine has discovered a possible molecular signature of coronary artery disease in bone marrow stem cells. The dramatic findings were presented on November 16 at the American Heart Association's Scientific Sessions in Orlando.

Coronary artery disease remains the number one killer in the United States and much of the Western world. It is characterized by a buildup of plaque that narrows blood vessels leading to and from the heart, but how the disease develops is still poorly understood. One long-held hypothesis is that the ability of the bone marrow to continuously release cells that repair vascular damage, preventing plaque buildup, somehow goes awry in people with coronary artery disease.

To test this hypothesis, the Miller School team isolated putative endothelial repair stem cells (called CD34+/Lin- cells) from bone marrow of patients with coronary artery disease, from patients undergoing cardiothoracic surgery for non-coronary artery related conditions, and from healthy volunteers. Using microarray technology, researchers profiled the isolated stem cells from five patients in each group for gene and micro-ribonucleic acid (RNA) expression and found a dramatic up-regulation of 14 micro-RNAs in the cells from patients with coronary artery disease. Micro-RNAs are a newly discovered class of molecules in eukaryotic cells that are thought to regulate upwards of 40 percent of genes in the human genome and may provide mechanisms for the global coordination and integration of complex pathways involved in development and disease.

Keith Webster, Ph.D., director of the Vascular Biology Institute and Walter G. Ross Distinguished Chair of Vascular Biology at the Miller School, says the up-regulation may cause the stem cells to lose their reparative function.

"What's so remarkable about the findings is that five of the 14 micro-RNA's targeted genes essential for stem cell survival, self renewal, proliferation and the induction of angiogenesis (vascular repair and growth) were affected,'' Webster says. "This probably leaves these cells 'functionally crippled" and unable to perform the ongoing vascular repair for which they are responsible."

The scientists say the results provide a unique insight into the molecular etiology of coronary artery disease. The findings also offer a major boost and new hope for stem cell technology for the treatment of coronary artery disease and related peripheral artery disease.

"Moving forward, our research team will try to determine if the function and reparative properties of the CD34+/Lin-cells can be recovered through medication or even by direct manipulation of the micro-RNAs through gene therapy," Webster says. "If so we will be able to develop vastly improved stem cell therapy for patients with acute myocardial infarction, and we will be a step closer to a mechanistic understanding, and perhaps an equivalent stem cell therapy for coronary artery disease, that will preempt acute MI."

The study, which has been submitted for publication in The New England Journal of Medicine, involved researchers and scientists from the Department of Molecular and Cellular Pharmacology, the Cardiovascular Division., the Division of Cardiothoracic Surgery, the Division of Transplantation, the angioplasty lab and organ procurement.

Source
University of Miami Miller School of Medicine

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