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

3 Citations (Scopus)

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)
JournalCardiovascular Drugs and Therapy
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Adipose Tissue
Atherosclerosis
Tissue Transplantation
Abdominal Aorta
Obesity
High Fat Diet
Thoracic Aorta
Vascular Diseases
Blood Vessels
Insulin Resistance
Myography
Body Weight
Tissue Expansion
Inflammation
Lipids
Glucose
Adventitia
Adipokines
Intra-Abdominal Fat
LDL Receptors

Keywords

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

ASJC Scopus subject areas

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

Cite this

Horimatsu, T., Patel, A. S., Prasad, R., Reid, L. E., Benson, T. W., Zarzour, A., ... Weintraub, N. L. (Accepted/In press). Remote Effects of Transplanted Perivascular Adipose Tissue on Endothelial Function and Atherosclerosis. Cardiovascular Drugs and Therapy. https://doi.org/10.1007/s10557-018-6821-y

Remote Effects of Transplanted Perivascular Adipose Tissue on Endothelial Function and Atherosclerosis. / Horimatsu, Tetsuo; Patel, Aaron S.; Prasad, Rosaria; Reid, Lauren E.; Benson, Tyler W.; Zarzour, Abdalrahman; Ogbi, Mourad; Bruder do Nascimento, Thiago; Belin de Chantemele, Eric; Stansfield, Brian K.; Lu, Xin Yun; Kim, Ha Won; Weintraub, Neal L.

In: Cardiovascular Drugs and Therapy, 01.01.2018.

Research output: Contribution to journalArticle

Horimatsu, T, Patel, AS, Prasad, R, Reid, LE, Benson, TW, Zarzour, A, Ogbi, M, Bruder do Nascimento, T, Belin de Chantemele, E, Stansfield, BK, Lu, XY, Kim, HW & Weintraub, NL 2018, 'Remote Effects of Transplanted Perivascular Adipose Tissue on Endothelial Function and Atherosclerosis', Cardiovascular Drugs and Therapy. https://doi.org/10.1007/s10557-018-6821-y
Horimatsu, Tetsuo ; Patel, Aaron S. ; Prasad, Rosaria ; Reid, Lauren E. ; Benson, Tyler W. ; Zarzour, Abdalrahman ; Ogbi, Mourad ; Bruder do Nascimento, Thiago ; Belin de Chantemele, Eric ; Stansfield, Brian K. ; Lu, Xin Yun ; Kim, Ha Won ; Weintraub, Neal L. / Remote Effects of Transplanted Perivascular Adipose Tissue on Endothelial Function and Atherosclerosis. In: Cardiovascular Drugs and Therapy. 2018.
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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.",
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T1 - Remote Effects of Transplanted Perivascular Adipose Tissue on Endothelial Function and Atherosclerosis

AU - Horimatsu, Tetsuo

AU - Patel, Aaron S.

AU - Prasad, Rosaria

AU - Reid, Lauren E.

AU - Benson, Tyler W.

AU - Zarzour, Abdalrahman

AU - Ogbi, Mourad

AU - Bruder do Nascimento, Thiago

AU - Belin de Chantemele, Eric

AU - Stansfield, Brian K.

AU - Lu, Xin Yun

AU - Kim, Ha Won

AU - Weintraub, Neal L.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Atherosclerosis

KW - Endothelial dysfunction

KW - Fat transplantation

KW - Inflammation

KW - Perivascular adipose tissue

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SN - 0920-3206

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