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Remote Effects of Transplanted Perivascular Adipose Tissue on Endothelial Function and Atherosclerosis

  • Tetsuo Horimatsu
  • Aaron S. Patel
  • Rosaria Prasad
  • Lauren E. Reid
  • Tyler W. Benson
  • Abdalrahman Zarzour
  • Mourad Ogbi
  • Thiago Bruder do Nascimento
  • Eric Belin de Chantemele
  • Brian K. Stansfield
  • Xin-Yun Lu
  • Ha Won Kim
  • Neal L. Weintraub
ORIGINAL ARTICLE
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Abstract

Purpose

Perivascular adipose tissue (PVAT) surrounds the arterial adventitia and plays an important role in vascular homeostasis. PVAT expands in obesity, and inflamed PVAT can locally promote endothelial dysfunction and atherosclerosis. Here, using adipose tissue transplantation, we tested the hypothesis that expansion of PVAT can also remotely exacerbate vascular disease.

Methods

Fifty milligrams of abdominal aortic PVAT was isolated from high-fat diet (HFD)-fed wild-type mice and transplanted onto the abdominal aorta of lean LDL receptor knockout mice. Subcutaneous and visceral adipose tissues were used as controls. After HFD feeding for 10 weeks, body weight, glucose/insulin sensitivity, and lipid levels were measured. Adipocytokine gene expression was assessed in the transplanted adipose tissues, and the thoracic aorta was harvested to quantify atherosclerotic lesions by Oil-Red O staining and to assess vasorelaxation by wire myography.

Results

PVAT transplantation did not influence body weight, fat composition, lipid levels, or glucose/insulin sensitivity. However, as compared with controls, transplantation of PVAT onto the abdominal aorta increased thoracic aortic atherosclerosis. Furthermore, PVAT transplantation onto the abdominal aorta inhibited endothelium-dependent relaxation in the thoracic aorta. MCP-1 and TNF-α expression was elevated, while adiponectin expression was reduced, in the transplanted PVAT tissue, suggesting augmented inflammation as a potential mechanism for the remote vascular effects of transplanted PVAT.

Conclusions

These data suggest that PVAT expansion and inflammation in obesity can remotely induce endothelial dysfunction and augment atherosclerosis. Identifying the underlying mechanisms may lead to novel approaches for risk assessment and treatment of obesity-related vascular disease.

Keywords

Perivascular adipose tissue Fat transplantation Endothelial dysfunction Atherosclerosis Inflammation 

Notes

Funding

This study was funded by grants HL124097, HL126949, HL134354, and AR070029 from the National Institutes of Health (N.L.W).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants.

Supplementary material

10557_2018_6821_MOESM1_ESM.docx (13 kb)
Supplemental Table 1 (DOCX 12 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Tetsuo Horimatsu
    • 1
  • Aaron S. Patel
    • 1
  • Rosaria Prasad
    • 1
  • Lauren E. Reid
    • 1
  • Tyler W. Benson
    • 1
  • Abdalrahman Zarzour
    • 1
  • Mourad Ogbi
    • 1
  • Thiago Bruder do Nascimento
    • 1
  • Eric Belin de Chantemele
    • 1
  • Brian K. Stansfield
    • 2
  • Xin-Yun Lu
    • 3
  • Ha Won Kim
    • 1
  • Neal L. Weintraub
    • 1
  1. 1.Department of Medicine, Cardiology Division, Vascular Biology CenterMedical College of Georgia at Augusta UniversityAugustaUSA
  2. 2.Pediatrics and Vascular Biology CenterMedical College of Georgia at Augusta UniversityAugustaUSA
  3. 3.Department of Neuroscience and Regenerative MedicineMedical College of Georgia at Augusta UniversityAugustaUSA

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