Haploinsufficiency of the insulin-like growth factor-1 receptor enhances endothelial repair and favorably modifies angiogenic progenitor cell phenotype

Nadira Y. Yuldasheva, Sheikh Tawqeer Rashid, Natalie J. Haywood, Paul Cordell, Romana Mughal, Hema Viswambharan, Helen Imrie, Piruthivi Sukumar, Richard M. Cubbon, Amir Aziz, Matthew Gage, Kamatamu Amanda Mbonye, Jessica Smith, Stacey Galloway, Anna Skromna, D. Julian A. Scott, Mark T. Kearney, Stephen B. Wheatcroft

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

OBJECTIVES - Defective endothelial regeneration predisposes to adverse arterial remodeling and is thought to contribute to cardiovascular disease in type 2 diabetes mellitus. We recently demonstrated that the type 1 insulin-like growth factor receptor (IGF1R) is a negative regulator of insulin sensitivity and nitric oxide bioavailability. In this report, we examined partial deletion of the IGF1R as a potential strategy to enhance endothelial repair. APPROACH AND RESULTS - We assessed endothelial regeneration after wire injury in mice and abundance and function of angiogenic progenitor cells in mice with haploinsufficiency of the IGF1R (IGF1R). Endothelial regeneration after arterial injury was accelerated in IGF1R mice. Although the yield of angiogenic progenitor cells was lower in IGF1R mice, these angiogenic progenitor cells displayed enhanced adhesion, increased secretion of insulin-like growth factor-1, and enhanced angiogenic capacity. To examine the relevance of IGF1R manipulation to cell-based therapy, we transfused IGF1R bone marrow-derived CD117 cells into wild-type mice. IGF1R cells accelerated endothelial regeneration after arterial injury compared with wild-type cells and did not alter atherosclerotic lesion formation. CONCLUSIONS - Haploinsufficiency of the IGF1R is associated with accelerated endothelial regeneration in vivo and enhanced tube forming and adhesive potential of angiogenic progenitor cells in vitro. Partial deletion of IGF1R in transfused bone marrow-derived CD117 cells enhanced their capacity to promote endothelial regeneration without altering atherosclerosis. Our data suggest that manipulation of the IGF1R could be exploited as novel therapeutic approach to enhance repair of the arterial wall after injury.

LanguageEnglish
Pages2051-2058
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume34
Issue number9
Early online date10 Jul 2014
DOIs
Publication statusPublished - 1 Sep 2014
Externally publishedYes

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Somatomedin Receptors
Haploinsufficiency
Regeneration
Stem Cells
Phenotype
Wounds and Injuries
Bone Marrow
IGF Type 1 Receptor
Somatomedins
Cell- and Tissue-Based Therapy
Adhesives
Type 2 Diabetes Mellitus
Biological Availability
Insulin Resistance
Atherosclerosis
Nitric Oxide
Cardiovascular Diseases
Endothelial Cells

Cite this

Yuldasheva, Nadira Y. ; Rashid, Sheikh Tawqeer ; Haywood, Natalie J. ; Cordell, Paul ; Mughal, Romana ; Viswambharan, Hema ; Imrie, Helen ; Sukumar, Piruthivi ; Cubbon, Richard M. ; Aziz, Amir ; Gage, Matthew ; Mbonye, Kamatamu Amanda ; Smith, Jessica ; Galloway, Stacey ; Skromna, Anna ; Scott, D. Julian A. ; Kearney, Mark T. ; Wheatcroft, Stephen B. / Haploinsufficiency of the insulin-like growth factor-1 receptor enhances endothelial repair and favorably modifies angiogenic progenitor cell phenotype. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2014 ; Vol. 34, No. 9. pp. 2051-2058.
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abstract = "OBJECTIVES - Defective endothelial regeneration predisposes to adverse arterial remodeling and is thought to contribute to cardiovascular disease in type 2 diabetes mellitus. We recently demonstrated that the type 1 insulin-like growth factor receptor (IGF1R) is a negative regulator of insulin sensitivity and nitric oxide bioavailability. In this report, we examined partial deletion of the IGF1R as a potential strategy to enhance endothelial repair. APPROACH AND RESULTS - We assessed endothelial regeneration after wire injury in mice and abundance and function of angiogenic progenitor cells in mice with haploinsufficiency of the IGF1R (IGF1R). Endothelial regeneration after arterial injury was accelerated in IGF1R mice. Although the yield of angiogenic progenitor cells was lower in IGF1R mice, these angiogenic progenitor cells displayed enhanced adhesion, increased secretion of insulin-like growth factor-1, and enhanced angiogenic capacity. To examine the relevance of IGF1R manipulation to cell-based therapy, we transfused IGF1R bone marrow-derived CD117 cells into wild-type mice. IGF1R cells accelerated endothelial regeneration after arterial injury compared with wild-type cells and did not alter atherosclerotic lesion formation. CONCLUSIONS - Haploinsufficiency of the IGF1R is associated with accelerated endothelial regeneration in vivo and enhanced tube forming and adhesive potential of angiogenic progenitor cells in vitro. Partial deletion of IGF1R in transfused bone marrow-derived CD117 cells enhanced their capacity to promote endothelial regeneration without altering atherosclerosis. Our data suggest that manipulation of the IGF1R could be exploited as novel therapeutic approach to enhance repair of the arterial wall after injury.",
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author = "Yuldasheva, {Nadira Y.} and Rashid, {Sheikh Tawqeer} and Haywood, {Natalie J.} and Paul Cordell and Romana Mughal and Hema Viswambharan and Helen Imrie and Piruthivi Sukumar and Cubbon, {Richard M.} and Amir Aziz and Matthew Gage and Mbonye, {Kamatamu Amanda} and Jessica Smith and Stacey Galloway and Anna Skromna and Scott, {D. Julian A.} and Kearney, {Mark T.} and Wheatcroft, {Stephen B.}",
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Yuldasheva, NY, Rashid, ST, Haywood, NJ, Cordell, P, Mughal, R, Viswambharan, H, Imrie, H, Sukumar, P, Cubbon, RM, Aziz, A, Gage, M, Mbonye, KA, Smith, J, Galloway, S, Skromna, A, Scott, DJA, Kearney, MT & Wheatcroft, SB 2014, 'Haploinsufficiency of the insulin-like growth factor-1 receptor enhances endothelial repair and favorably modifies angiogenic progenitor cell phenotype', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 34, no. 9, pp. 2051-2058. https://doi.org/10.1161/ATVBAHA.114.304121

Haploinsufficiency of the insulin-like growth factor-1 receptor enhances endothelial repair and favorably modifies angiogenic progenitor cell phenotype. / Yuldasheva, Nadira Y.; Rashid, Sheikh Tawqeer; Haywood, Natalie J.; Cordell, Paul; Mughal, Romana; Viswambharan, Hema; Imrie, Helen; Sukumar, Piruthivi; Cubbon, Richard M.; Aziz, Amir; Gage, Matthew; Mbonye, Kamatamu Amanda; Smith, Jessica; Galloway, Stacey; Skromna, Anna; Scott, D. Julian A.; Kearney, Mark T.; Wheatcroft, Stephen B.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 34, No. 9, 01.09.2014, p. 2051-2058.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Haploinsufficiency of the insulin-like growth factor-1 receptor enhances endothelial repair and favorably modifies angiogenic progenitor cell phenotype

AU - Yuldasheva, Nadira Y.

AU - Rashid, Sheikh Tawqeer

AU - Haywood, Natalie J.

AU - Cordell, Paul

AU - Mughal, Romana

AU - Viswambharan, Hema

AU - Imrie, Helen

AU - Sukumar, Piruthivi

AU - Cubbon, Richard M.

AU - Aziz, Amir

AU - Gage, Matthew

AU - Mbonye, Kamatamu Amanda

AU - Smith, Jessica

AU - Galloway, Stacey

AU - Skromna, Anna

AU - Scott, D. Julian A.

AU - Kearney, Mark T.

AU - Wheatcroft, Stephen B.

PY - 2014/9/1

Y1 - 2014/9/1

N2 - OBJECTIVES - Defective endothelial regeneration predisposes to adverse arterial remodeling and is thought to contribute to cardiovascular disease in type 2 diabetes mellitus. We recently demonstrated that the type 1 insulin-like growth factor receptor (IGF1R) is a negative regulator of insulin sensitivity and nitric oxide bioavailability. In this report, we examined partial deletion of the IGF1R as a potential strategy to enhance endothelial repair. APPROACH AND RESULTS - We assessed endothelial regeneration after wire injury in mice and abundance and function of angiogenic progenitor cells in mice with haploinsufficiency of the IGF1R (IGF1R). Endothelial regeneration after arterial injury was accelerated in IGF1R mice. Although the yield of angiogenic progenitor cells was lower in IGF1R mice, these angiogenic progenitor cells displayed enhanced adhesion, increased secretion of insulin-like growth factor-1, and enhanced angiogenic capacity. To examine the relevance of IGF1R manipulation to cell-based therapy, we transfused IGF1R bone marrow-derived CD117 cells into wild-type mice. IGF1R cells accelerated endothelial regeneration after arterial injury compared with wild-type cells and did not alter atherosclerotic lesion formation. CONCLUSIONS - Haploinsufficiency of the IGF1R is associated with accelerated endothelial regeneration in vivo and enhanced tube forming and adhesive potential of angiogenic progenitor cells in vitro. Partial deletion of IGF1R in transfused bone marrow-derived CD117 cells enhanced their capacity to promote endothelial regeneration without altering atherosclerosis. Our data suggest that manipulation of the IGF1R could be exploited as novel therapeutic approach to enhance repair of the arterial wall after injury.

AB - OBJECTIVES - Defective endothelial regeneration predisposes to adverse arterial remodeling and is thought to contribute to cardiovascular disease in type 2 diabetes mellitus. We recently demonstrated that the type 1 insulin-like growth factor receptor (IGF1R) is a negative regulator of insulin sensitivity and nitric oxide bioavailability. In this report, we examined partial deletion of the IGF1R as a potential strategy to enhance endothelial repair. APPROACH AND RESULTS - We assessed endothelial regeneration after wire injury in mice and abundance and function of angiogenic progenitor cells in mice with haploinsufficiency of the IGF1R (IGF1R). Endothelial regeneration after arterial injury was accelerated in IGF1R mice. Although the yield of angiogenic progenitor cells was lower in IGF1R mice, these angiogenic progenitor cells displayed enhanced adhesion, increased secretion of insulin-like growth factor-1, and enhanced angiogenic capacity. To examine the relevance of IGF1R manipulation to cell-based therapy, we transfused IGF1R bone marrow-derived CD117 cells into wild-type mice. IGF1R cells accelerated endothelial regeneration after arterial injury compared with wild-type cells and did not alter atherosclerotic lesion formation. CONCLUSIONS - Haploinsufficiency of the IGF1R is associated with accelerated endothelial regeneration in vivo and enhanced tube forming and adhesive potential of angiogenic progenitor cells in vitro. Partial deletion of IGF1R in transfused bone marrow-derived CD117 cells enhanced their capacity to promote endothelial regeneration without altering atherosclerosis. Our data suggest that manipulation of the IGF1R could be exploited as novel therapeutic approach to enhance repair of the arterial wall after injury.

KW - endothelium

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U2 - 10.1161/ATVBAHA.114.304121

DO - 10.1161/ATVBAHA.114.304121

M3 - Article

VL - 34

SP - 2051

EP - 2058

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

T2 - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 9

ER -