title: Slow and sustained nitric oxide releasing compounds inhibit multipotent vascular stem cell proliferation and differentiation without causing cell death.
abstract: 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.
authors.affiliation: Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859, USA.
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Curtis
authors.affiliation: Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859, USA.
authors.forename: Kyle Alexander
authors.initials: KA
authors.lastname: Leix
authors.affiliation: Department of Biomedical Science and Medicine, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Biology, Central Michigan University, Mount Pleasant, MI 48859, USA.
authors.forename: Richard Samuel Elliot
authors.initials: RS
authors.lastname: Glaves
authors.affiliation: Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Ash
authors.affiliation: Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859, USA. Electronic address: Mohan1dk@cmich.edu.
authors.forename: Dillip K
authors.initials: DK
authors.lastname: Mohanty
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats
chemical_list: D003692:Delayed-Action Preparations; D020030:Nitric Oxide Donors
keywords: Mesenchymal-like stem cells; Multipotent vascular stem cells; Slow and sustained nitric oxide donor; Smooth muscle cells; Stem cell proliferation and differentiation