Slow and sustained nitric oxide releasing compounds inhibit multipotent vascular stem cell proliferation and differentiation without causing cell death.
Atherosclerosis is the leading cause of cerebral and myocardial infarction. It is believed that neointimal growth common in the later stages of atherosclerosis is a result of vascular smooth muscle cell (SMC) de-differentiation in response to endothelial injury. However, the claims of the SMC de-differentiation theory have not been substantiated by monitoring the fate of mature SMCs in response to such injuries. A recent study suggests that atherosclerosis is a consequence of multipotent vascular stem cell (MVSC) differentiation. Nitric oxide (NO) is a well-known mediator against atherosclerosis, in part because of its inhibitory effect on SMC proliferation. Using three different NO-donors, we have investigated the effects of NO on MVSC proliferation. Results indicate that NO inhibits MVSC proliferation in a concentration dependent manner. A slow and sustained delivery of NO proved to inhibit proliferation without causing cell death. On the other hand, larger, single-burst NO concentrations, inhibits proliferation, with concurrent significant cell death. Furthermore, our results indicate that endogenously produced NO inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs) and subsequently to SMC as well.
['Curtis|Brandon M|BM|', 'Leix|Kyle Alexander|KA|', 'Ji|Yajing|Y|', 'Glaves|Richard Samuel Elliot|RS|', 'Ash|David E|DE|', 'Mohanty|Dillip K|DK|']
D000818:Animals D017209:Apoptosis D002454:Cell Differentiation D049109:Cell Proliferation D002478:Cells, Cultured D003692:Delayed-Action Preparations D059630:Mesenchymal Stem Cells D039902:Multipotent Stem Cells D032389:Myocytes, Smooth Muscle D020030:Nitric Oxide Donors D018384:Oxidative Stress D051381:Rats
Multipotent vascular stem cells Stem cell proliferation and differentiation Smooth muscle cells Mesenchymal-like stem cells Slow and sustained nitric oxide donor