Molecular evidence for arterial repair in atherosclerosis
Ravi Karra *, Sreekanth Vemullapalli *, Chunming Dong *, Edward E. Herderick , Xiaohua Song *, Kathy Slosek *, Joseph R. Nevins , , Mike West , ¶, Pascal J. Goldschmidt-Clermont *, and David Seo *
*Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC 27705; Biomedical Engineering, Ohio State University, Columbus, OH 43210; and Institutes for Genome Sciences and Policy and ¶Statistics and Decision Sciences and Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27705
Communicated by Robert J. Lefkowitz, Duke University Medical Center, Durham, NC, September 3, 2005 (received for review April 19, 2005)
Atherosclerosis is a chronic inflammatory process and progresses through characteristic morphologic stages. We have shown previously that chronically injecting bone-marrow-derived vascular progenitor cells can effect arterial repair. This repair capacity depends on the age of the injected marrow cells, suggesting a progressive decline in progenitor cell function. We hypothesized that the progression of atherosclerosis coincides with the deteriorating repair capacity of the bone marrow. Here, we ascribe patterns of gene expression that accurately and reproducibly identify specific disease states in murine atherosclerosis. We then use these expression patterns to determine the point in the disease process at which the repair of arteries by competent bone marrow cells ceases to be efficient. We show that the loss of the molecular signature for competent repair is concurrent with the initiation of atherosclerotic lesions. This work provides a previously unreported comprehensive molecular data set using broad-based analysis that links the loss of successful repair with the progression of a chronic illness. |
