Diabetes impairs the vascular recruitment of normal stem cells by oxidant damage, reversed by increases in pAMPK, Heme Oxygenase-1, and Adiponectin

Glanmario Sambuceti, Silvia Morbelli, Luca Vanella, Claudia Kusmic, Cecilia Marini, Michela Massollo, Carla Augerl, Mirko Corselli, Chiara Ghersl, Barbara Chiavarina, Luigi F. Rodella, Antonio L'abbate, George Drummond, Nader G. Abraham, Francesco Frassoni

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Background. Atherosclerosis progression is accelerated in diabetes mellitus (DM) by either direct endothelial damage or reduced availability and function of endothelial progenitor cells (EPCs). Both alterations are related to increased oxidant damage. Aim. We examined if DM specifically impairs vascular signaling, thereby reducing the recruitment of normal EPCs, and if increases in antioxidant levels by induction of heme oxygenase-1 (HO-1) can reverse this condition. Methods. Control and diabetic rats were treated with the HO-1 inducer cobalt protoporphyrin (CoPP) once a week for 3 weeks. Eight weeks after the development of diabetes, EPCs harvested from the aorta of syngenic inbred normal rats and labeled with technetium-99m-exametazime were infused via the femoral vein to estimate their blood clearance and aortic recruitment. Circulating endothelial cells (CECs) and the aortic expression of thrombomodulin (TM), CD31, and endothelial nitric oxide synthase (eNOS) were used to measure endothelial damage. Results. DM reduced blood clearance and aortic recruitment of EPCs. Both parameters were returned to control levels by CoPP treatment without affecting EPC kinetics in normal animals. These abnormalities of EPCs in DM were paralleled by reduced serum adiponectin levels, increased numbers of CECs, reduced endothelial expression of phos-phorylated eNOS, and reduced levels of TM, CD31, and phosphorylated AMP-activated protein kinase (pAMPK). CoPP treatment restored all of these parameters to normal levels. Conclusion. Type II DM and its related oxidant damage hamper the interaction between the vascular wall and normal EPCs by mechanisms that are, at least partially, reversed by the induction of HO-1 gene expression, adiponee- tin, and pAMPK levels.STEM CELLS 2009;27:399-407

Original languageEnglish
Pages (from-to)399-407
Number of pages9
JournalStem Cells
Volume27
Issue number2
DOIs
Publication statusPublished - Feb 2009

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AMP-Activated Protein Kinases
Heme Oxygenase-1
Adiponectin
Oxidants
Blood Vessels
Stem Cells
Diabetes Mellitus
Thrombomodulin
Nitric Oxide Synthase Type III
Endothelial Cells
Scanning Transmission Electron Microscopy
Femoral Vein
Tin
Technetium
Endothelial Progenitor Cells
Type 2 Diabetes Mellitus
Aorta
Atherosclerosis
Antioxidants
Gene Expression

Keywords

  • CD31
  • Endothelial progenitor cells
  • HO-1
  • NO
  • pAMPK
  • Vascular repair

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Diabetes impairs the vascular recruitment of normal stem cells by oxidant damage, reversed by increases in pAMPK, Heme Oxygenase-1, and Adiponectin. / Sambuceti, Glanmario; Morbelli, Silvia; Vanella, Luca; Kusmic, Claudia; Marini, Cecilia; Massollo, Michela; Augerl, Carla; Corselli, Mirko; Ghersl, Chiara; Chiavarina, Barbara; Rodella, Luigi F.; L'abbate, Antonio; Drummond, George; Abraham, Nader G.; Frassoni, Francesco.

In: Stem Cells, Vol. 27, No. 2, 02.2009, p. 399-407.

Research output: Contribution to journalArticle

Sambuceti, G, Morbelli, S, Vanella, L, Kusmic, C, Marini, C, Massollo, M, Augerl, C, Corselli, M, Ghersl, C, Chiavarina, B, Rodella, LF, L'abbate, A, Drummond, G, Abraham, NG & Frassoni, F 2009, 'Diabetes impairs the vascular recruitment of normal stem cells by oxidant damage, reversed by increases in pAMPK, Heme Oxygenase-1, and Adiponectin', Stem Cells, vol. 27, no. 2, pp. 399-407. https://doi.org/10.1634/stemcells.2008-0800
Sambuceti, Glanmario ; Morbelli, Silvia ; Vanella, Luca ; Kusmic, Claudia ; Marini, Cecilia ; Massollo, Michela ; Augerl, Carla ; Corselli, Mirko ; Ghersl, Chiara ; Chiavarina, Barbara ; Rodella, Luigi F. ; L'abbate, Antonio ; Drummond, George ; Abraham, Nader G. ; Frassoni, Francesco. / Diabetes impairs the vascular recruitment of normal stem cells by oxidant damage, reversed by increases in pAMPK, Heme Oxygenase-1, and Adiponectin. In: Stem Cells. 2009 ; Vol. 27, No. 2. pp. 399-407.
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AU - Sambuceti, Glanmario

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AU - Vanella, Luca

AU - Kusmic, Claudia

AU - Marini, Cecilia

AU - Massollo, Michela

AU - Augerl, Carla

AU - Corselli, Mirko

AU - Ghersl, Chiara

AU - Chiavarina, Barbara

AU - Rodella, Luigi F.

AU - L'abbate, Antonio

AU - Drummond, George

AU - Abraham, Nader G.

AU - Frassoni, Francesco

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N2 - Background. Atherosclerosis progression is accelerated in diabetes mellitus (DM) by either direct endothelial damage or reduced availability and function of endothelial progenitor cells (EPCs). Both alterations are related to increased oxidant damage. Aim. We examined if DM specifically impairs vascular signaling, thereby reducing the recruitment of normal EPCs, and if increases in antioxidant levels by induction of heme oxygenase-1 (HO-1) can reverse this condition. Methods. Control and diabetic rats were treated with the HO-1 inducer cobalt protoporphyrin (CoPP) once a week for 3 weeks. Eight weeks after the development of diabetes, EPCs harvested from the aorta of syngenic inbred normal rats and labeled with technetium-99m-exametazime were infused via the femoral vein to estimate their blood clearance and aortic recruitment. Circulating endothelial cells (CECs) and the aortic expression of thrombomodulin (TM), CD31, and endothelial nitric oxide synthase (eNOS) were used to measure endothelial damage. Results. DM reduced blood clearance and aortic recruitment of EPCs. Both parameters were returned to control levels by CoPP treatment without affecting EPC kinetics in normal animals. These abnormalities of EPCs in DM were paralleled by reduced serum adiponectin levels, increased numbers of CECs, reduced endothelial expression of phos-phorylated eNOS, and reduced levels of TM, CD31, and phosphorylated AMP-activated protein kinase (pAMPK). CoPP treatment restored all of these parameters to normal levels. Conclusion. Type II DM and its related oxidant damage hamper the interaction between the vascular wall and normal EPCs by mechanisms that are, at least partially, reversed by the induction of HO-1 gene expression, adiponee- tin, and pAMPK levels.STEM CELLS 2009;27:399-407

AB - Background. Atherosclerosis progression is accelerated in diabetes mellitus (DM) by either direct endothelial damage or reduced availability and function of endothelial progenitor cells (EPCs). Both alterations are related to increased oxidant damage. Aim. We examined if DM specifically impairs vascular signaling, thereby reducing the recruitment of normal EPCs, and if increases in antioxidant levels by induction of heme oxygenase-1 (HO-1) can reverse this condition. Methods. Control and diabetic rats were treated with the HO-1 inducer cobalt protoporphyrin (CoPP) once a week for 3 weeks. Eight weeks after the development of diabetes, EPCs harvested from the aorta of syngenic inbred normal rats and labeled with technetium-99m-exametazime were infused via the femoral vein to estimate their blood clearance and aortic recruitment. Circulating endothelial cells (CECs) and the aortic expression of thrombomodulin (TM), CD31, and endothelial nitric oxide synthase (eNOS) were used to measure endothelial damage. Results. DM reduced blood clearance and aortic recruitment of EPCs. Both parameters were returned to control levels by CoPP treatment without affecting EPC kinetics in normal animals. These abnormalities of EPCs in DM were paralleled by reduced serum adiponectin levels, increased numbers of CECs, reduced endothelial expression of phos-phorylated eNOS, and reduced levels of TM, CD31, and phosphorylated AMP-activated protein kinase (pAMPK). CoPP treatment restored all of these parameters to normal levels. Conclusion. Type II DM and its related oxidant damage hamper the interaction between the vascular wall and normal EPCs by mechanisms that are, at least partially, reversed by the induction of HO-1 gene expression, adiponee- tin, and pAMPK levels.STEM CELLS 2009;27:399-407

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