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

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)503-510
Number of pages8
JournalCardiovascular Drugs and Therapy
Volume32
Issue number5
DOIs
StatePublished - Oct 1 2018

Keywords

  • Atherosclerosis
  • Endothelial dysfunction
  • Fat transplantation
  • Inflammation
  • Perivascular adipose tissue

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

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    Horimatsu, T., Patel, A. S., Prasad, R., Reid, L. E., Benson, T. W., Zarzour, A., Ogbi, M., Bruder do Nascimento, T., Belin de Chantemele, E., Stansfield, B. K., Lu, X. Y., Kim, H. W., & Weintraub, N. L. (2018). Remote Effects of Transplanted Perivascular Adipose Tissue on Endothelial Function and Atherosclerosis. Cardiovascular Drugs and Therapy, 32(5), 503-510. https://doi.org/10.1007/s10557-018-6821-y