Regulation of CD73 in the development of lower limb atherosclerosis.
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.
Department of Vascular Surgery, Turku University Hospital, Hämeenkatu 11, 20521, Turku, Finland. juho.jalkanen@utu.fi.
Juho
0000-0002-1693-8293
J
Jalkanen
MediCity Research Laboratory, Department of Microbiology and Immunology, University of Turku, Tykistönkatu 6A, 20520, Turku, Finland.
Maija
M
Hollmén
MediCity Research Laboratory, Department of Microbiology and Immunology, University of Turku, Tykistönkatu 6A, 20520, Turku, Finland.
Sirpa
S
Jalkanen
Department of Vascular Surgery, Turku University Hospital, Hämeenkatu 11, 20521, Turku, Finland.
Harri
H
Hakovirta
D015720:5'-Nucleotidase / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D035002:Lower Extremity; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000378:metabolism*; D015398:Signal Transduction
D015720:5'-Nucleotidase
Atherosclerosis; CD73; Peripheral artery disease; Purinergic signaling; Vasa vasorum