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Regulation of CD73 in the development of lower limb atherosclerosis

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Abstract

Atherosclerosis is an inflammatory process of the arterial wall. CD73 (also known as ecto-5′-nucleotidase) is a key regulator of cell signaling in response to inflammation and hypoxia, and may be important in the development of atherosclerosis. Recently, we have shown that high CD73 activity can be detected in the serum of patients with peripheral arterial disease (PAD). Using this same PAD patient cohort of 226 subjects with 38 femoral artery samples obtained during surgical endarcterectomy and control artery samples taken during autopsy, we explored the association of serum CD73 activity with overall atherosclerotic burden and the expression of CD73 in mature and developing plaques. Interestingly, we found that CD73 activity had a tendency to increase along with more severe presentation of PAD (from 249 nmol/mL/h in moderate disease to 332 nmol/mL/h in severe disease; P = 0.013) and that CD73 expression is elevated in the vasa vasorum of developing plaques, but completely lost in mature occlusive plaques removed during endarcterectomy (P < 0.001). The current findings implicate that as a result of shedding and loss of CD73 from the arterial wall, CD73 activity is elevated in the serum of patients with widespread atherosclerosis. These findings highlight the importance of a better understanding of the local role of CD73 in the development and maturation of arterial atherosclerotic plaques in man.

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Abbreviations

PAD:

Peripheral artery disease

TASC II:

The second Trans-Atlantic Inter-Society Consensus for the management of peripheral artery disease

P-AFOS:

Plasma alkaline phosphatase

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Acknowledgements

From the MediCity Research Laboratory of Turku University (Turku, Finland), we thank Sari Mäki and Teija Kanasuo for technical assistance and PhD Gennady G. Yegutkin for analyses of CD73 activity in serum samples. From the Department of Pathology of Turku University Hospital, we thank Dr. Heikki Aho and Dr. Markku Kallajoki for the supply of autopsy samples.

Authors’ contributions

Initial idea and study design by JJ. HH and JJ collected the data. JJ, MH, and SJ contributed to the analysis of data. All authors were involved in preparing the manuscript and read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Vascular Surgery, Turku University Hospital, Hämeenkatu 11, 20521, Turku, Finland

    Juho Jalkanen & Harri Hakovirta

  2. MediCity Research Laboratory, Department of Microbiology and Immunology, University of Turku, Tykistönkatu 6A, 20520, Turku, Finland

    Maija Hollmén & Sirpa Jalkanen

Authors
  1. Juho Jalkanen
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  2. Maija Hollmén
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  3. Sirpa Jalkanen
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  4. Harri Hakovirta
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Corresponding author

Correspondence to Juho Jalkanen.

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Funding

The study was supported by the Academy of Finland, the Sigrid Juselius Foundation, Orion Research Foundation, and the Clinical Research Fund (EVO) of Turku University Hospital. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.

Conflicts of interest

Juho Jalkanen declares that he/she has no conflict of interest.

Maija Hollmén declares that he/she has no conflict of interest.

Sirpa Jalkanen declares that he/she has no conflict of interest.

Harri Hakovirta declares that he/she has no conflict of interest.

Ethical approval

The study has been approved by the Ethical Committee of the Hospital District of South-West Finland and the study has been conducted according to the Decleration of Helsinki.

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Jalkanen, J., Hollmén, M., Jalkanen, S. et al. Regulation of CD73 in the development of lower limb atherosclerosis. Purinergic Signalling 13, 127–134 (2017). https://doi.org/10.1007/s11302-016-9545-0

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