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Rab27a Regulates Human Perivascular Adipose Progenitor Cell Differentiation

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Abstract

Purpose

Perivascular adipose tissue (PVAT) surrounds blood vessels and regulates vascular tone through paracrine secretion of cytokines. During conditions promoting cardiometabolic dysfunction, such as obesity, cytokine secretion is altered towards a proinflammatory and proatherogenic profile. Despite the clinical implications for cardiovascular disease, studies addressing the biology of human PVAT remain limited. We are interested in characterizing the resident adipose progenitor cells (APCs) because of their potential role in PVAT expansion during obesity. We also focused on proteins regulating paracrine interactions, including the small GTPase Rab27a, which regulates protein trafficking and secretion.

Methods

PVAT from the ascending aorta was collected from patients with severe cardiovascular disease undergoing coronary artery bypass grafting (CABG). Freshly-isolated PVAT was digested and APC expanded in culture for characterizing progenitor markers, evaluating adipogenic potential and assessing the function(s) of Rab27a.

Results

Using flow cytometry, RT-PCR, and immunoblot, we characterized APC from human PVAT as negative for CD45 and CD31 and expressing CD73, CD105, and CD140A. These APCs differentiate into multilocular, UCP1-producing adipocytes in vitro. Rab27a was detected in interstitial cells of human PVAT in vivo and along F-actin tracks of PVAT-APC in vitro. Knockdown of Rab27a using siRNA in PVAT-APC prior to induction resulted in a marked reduction in lipid accumulation and reduced expression of adipogenic differentiation markers.

Conclusions

PVAT-APC from CABG donors express common adipocyte progenitor markers and differentiate into UCP1-containing adipocytes. Rab27a has an endogenous role in promoting the maturation of adipocytes from human PVAT-derived APC.

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Funding

This research was supported by NIH grant R01HL141149 (L. Liaw, PI) and American Heart Association grant 17GRNT33670972 (L. Liaw, PI). JB was partially supported by a pilot project from NIH grant 5P30GM106391, which also supported the Progenitor Cell Analysis Core, which was used for flow cytometry (R. Friesel PI). This work was also supported by our Histopathology and Histomorphometry Core, which is supported by NIH grants P20GM121301 (L. Liaw, PI), P30GM106391 (R. Friesel, PI), and U54GM115516 (C. Rosen, PI).

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Authors and Affiliations

  1. Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME, 04072, USA

    Joshua M. Boucher, Michael Robich, S. Spencer Scott, Xuehui Yang, Larisa Ryzhova, Jacqueline E. Turner, Ilka Pinz & Lucy Liaw

  2. Division of Thoracic and Cardiac Surgery, Maine Medical Center, Portland, ME, 04102, USA

    Michael Robich

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  1. Joshua M. Boucher
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  2. Michael Robich
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  3. S. Spencer Scott
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  4. Xuehui Yang
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  8. Lucy Liaw
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Correspondence to Lucy Liaw.

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The authors declare that they have no conflict of interest.

Ethical Approval

This study utilized human tissue that was procured via our Maine Medical Center Biobank, which provides de-identified samples. This study was reviewed and deemed exempt by our Maine Medical Center Institutional Review Board. The BioBank protocols are in accordance with the ethical standards of our institution and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individuals for de-identified use of their samples for research purposes.

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Boucher, J.M., Robich, M., Scott, S.S. et al. Rab27a Regulates Human Perivascular Adipose Progenitor Cell Differentiation. Cardiovasc Drugs Ther 32, 519–530 (2018). https://doi.org/10.1007/s10557-018-6813-y

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