title: Bone marrow mononuclear cell angiogenic competency is suppressed by a high-salt diet.
abstract: Autologous bone marrow-derived mononuclear cell (BM-MNC) transplantation is a potential therapy for inducing revascularization in ischemic tissues providing the underlying disease process had not negatively affected BM-MNC function. Previously, we have shown that skeletal muscle angiogenesis induced by electrical stimulation is impaired by a high-salt diet (HSD; 4% NaCl) in Sprague-Dawley (SD) rats. In this study we tested the hypothesis that BM-MNC angiogenic function is impaired by an elevated dietary sodium intake. Following 1 wk on HSD, either vehicle or BM-MNCs derived from SD donor rats on HSD or normal salt diet (NSD; 0.4% NaCl) were injected into male SD rats undergoing hindlimb stimulation. Administration of BM-MNCs (intramuscular or intravenous) from NSD donors, but not HSD donors, restored the angiogenic response in HSD recipients. Angiotensin II (3 ng · kg(-1) · min(-1)) infusion of HSD donor rats restored angiogenic capacity of BM-MNCs, and treatment of NSD donor rats with losartan, an angiotensin II receptor-1 antagonist, inhibited BM-MNC angiogenic competency. HSD BM-MNCs and NSD losartan BM-MNCs exhibited increased apoptosis in vitro following an acute 6-h hypoxic stimulus. HSD BM-MNCs also had increased apoptosis following injection into skeletal muscle. This study suggests that BM-MNC transplantation can restore skeletal muscle angiogenesis and that HSD impairs the angiogenic competency of BM-MNCs due to suppression of the renin-angiotensin system causing increased apoptosis.
authors.affiliation: Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, Wisconsin; and.
authors.forename: Jamie R
authors.initials: JR
authors.lastname: Karcher
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Greene
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002478:Cells, Cultured; D004558:Electric Stimulation / Q000379:methods; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D017673:Sodium Chloride, Dietary
keywords: angiogenesis; bone marrow mononuclear cells; high-salt diet; renin-angiotensin system