MedicalResearch.com Interview with:
Rafael Kramann, MD, FASN
RWTH Aachen University
Division of Nephrology and Clinical Immunology
52074 Aachen, Germany
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Vascular calcification contributes centrally to the increased cardiovascular morbidity and mortality in patients with diabetes or chronic kidney disease.
Vascular calcification is of major clinical importance as it predicts cardiovascular events, affects plaque stability contributing to stroke and myocardial infarction and also contributes to chronic heart failure by stiffening of the arterial wall. However, the cellular origin of vascular calcification is incompletely understood. While it is known that resident vascular smooth muscle cells and circulating macrophages are involved the contribution of adventitial cells is controversial and partly unknown.
Our data indicates that adventitial progenitor cells marked by expression of Gli1 are key drivers of vascular calcification in athero- and arteriosclerosis. Genetic ablation of this cell population completely abolished vascular calcification in a mouse model of high lipid load and chronic kidney disease. Identification of this progenitor population might be the first step towards a cell-specific targeted therapy of vascular calcification.
MedicalResearch.com: What should readers take away from your report?
Response: That adventitial mesenchymal stem cell-like progenitors are the cellular origin of calcification in the vascular wall.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Our data suggests that Gli1 is predominantly expressed in the adventitia of non-injured human arteries, however during vascular calcification in chronic kidney disease we observed strong Gli1 expression in the calcified arteries. In future studies it will be critical to evaluate whether this increased Gli1 expression is due to a similar progenitor population that exists in human arteries. Furthermore, studying pathways that regulat recruitment, expansion and differentiation of Gli1+ adventitial progenitors will be critical to develop novel therapeutics.
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Adventitial MSC-like Cells Are Progenitors of Vascular Smooth Muscle Cells and Drive Vascular Calcification in Chronic Kidney Disease
Rafael Kramann, Claudia Goettsch, Janewit Wongboonsin, …, Sanjay Jain, Elena Aikawa, Benjamin D. Humphreys
Kramann et al., 2016, Cell Stem Cell 19, 1–15 November 3, 2016 ª 2016 Elsevier Inc. http://dx.doi.org/10.1016/j.stem.2016.08.001
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