Transplanted perivascular adipose tissue accelerates injury-induced neointimal hyperplasia: Role of monocyte chemoattractant protein-1

David Manka, Tapan K. Chatterjee, Lynn L. Stoll, Joshua E. Basford, Eddy S. Konaniah, Ramprasad Srinivasan, Vladimir Y. Bogdanov, Yaoliang Tang, Andra L. Blomkalns, David Y. Hui, Neal L. Weintraub

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Objective - Perivascular adipose tissue (PVAT) expands during obesity, is highly inflamed, and correlates with coronary plaque burden and increased cardiovascular risk. We tested the hypothesis that PVAT contributes to the vascular response to wire injury and investigated the underlying mechanisms. Approach And Results - We transplanted thoracic aortic PVAT from donor mice fed a high-fat diet to the carotid arteries of recipient high-fat diet-fed low-density lipoprotein receptor knockout mice. Two weeks after transplantation, wire injury was performed, and animals were euthanized 2 weeks later. Immunohistochemistry was performed to quantify adventitial macrophage infiltration and neovascularization and neointimal lesion composition and size. Transplanted PVAT accelerated neointimal hyperplasia, adventitial macrophage infiltration, and adventitial angiogenesis. The majority of neointimal cells in PVAT-transplanted animals expressed α-smooth muscle actin, consistent with smooth muscle phenotype. Deletion of monocyte chemoattractant protein-1 in PVAT substantially attenuated the effects of fat transplantation on neointimal hyperplasia and adventitial angiogenesis, but not adventitial macrophage infiltration. Conditioned medium from perivascular adipocytes induced potent monocyte chemotaxis in vitro and angiogenic responses in cultured endothelial cells. Conclusions - These findings indicate that PVAT contributes to the vascular response to wire injury, in part through monocyte chemoattractant protein-1-dependent mechanisms.

Original languageEnglish (US)
Pages (from-to)1723-1730
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume34
Issue number8
DOIs
StatePublished - Aug 2014

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Chemokine CCL2
Adventitia
Hyperplasia
Adipose Tissue
Wounds and Injuries
Macrophages
High Fat Diet
Smooth Muscle
Blood Vessels
Transplantation
LDL Receptors
Chemotaxis
Conditioned Culture Medium
Carotid Arteries
Adipocytes
Knockout Mice
Actins
Monocytes
Cultured Cells
Thorax

Keywords

  • Adipose tissue
  • Hyperplasia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Transplanted perivascular adipose tissue accelerates injury-induced neointimal hyperplasia : Role of monocyte chemoattractant protein-1. / Manka, David; Chatterjee, Tapan K.; Stoll, Lynn L.; Basford, Joshua E.; Konaniah, Eddy S.; Srinivasan, Ramprasad; Bogdanov, Vladimir Y.; Tang, Yaoliang; Blomkalns, Andra L.; Hui, David Y.; Weintraub, Neal L.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 34, No. 8, 08.2014, p. 1723-1730.

Research output: Contribution to journalArticle

Manka, David ; Chatterjee, Tapan K. ; Stoll, Lynn L. ; Basford, Joshua E. ; Konaniah, Eddy S. ; Srinivasan, Ramprasad ; Bogdanov, Vladimir Y. ; Tang, Yaoliang ; Blomkalns, Andra L. ; Hui, David Y. ; Weintraub, Neal L. / Transplanted perivascular adipose tissue accelerates injury-induced neointimal hyperplasia : Role of monocyte chemoattractant protein-1. In: Arteriosclerosis, thrombosis, and vascular biology. 2014 ; Vol. 34, No. 8. pp. 1723-1730.
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AB - Objective - Perivascular adipose tissue (PVAT) expands during obesity, is highly inflamed, and correlates with coronary plaque burden and increased cardiovascular risk. We tested the hypothesis that PVAT contributes to the vascular response to wire injury and investigated the underlying mechanisms. Approach And Results - We transplanted thoracic aortic PVAT from donor mice fed a high-fat diet to the carotid arteries of recipient high-fat diet-fed low-density lipoprotein receptor knockout mice. Two weeks after transplantation, wire injury was performed, and animals were euthanized 2 weeks later. Immunohistochemistry was performed to quantify adventitial macrophage infiltration and neovascularization and neointimal lesion composition and size. Transplanted PVAT accelerated neointimal hyperplasia, adventitial macrophage infiltration, and adventitial angiogenesis. The majority of neointimal cells in PVAT-transplanted animals expressed α-smooth muscle actin, consistent with smooth muscle phenotype. Deletion of monocyte chemoattractant protein-1 in PVAT substantially attenuated the effects of fat transplantation on neointimal hyperplasia and adventitial angiogenesis, but not adventitial macrophage infiltration. Conditioned medium from perivascular adipocytes induced potent monocyte chemotaxis in vitro and angiogenic responses in cultured endothelial cells. Conclusions - These findings indicate that PVAT contributes to the vascular response to wire injury, in part through monocyte chemoattractant protein-1-dependent mechanisms.

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