TY - JOUR

T1 - CD73 rather than CD39 is mainly involved in controlling purinergic signaling in calcified aortic valve disease

AU - Kudryavtsev, Igor V.

AU - Serebriakova, Mariia

AU - Zhiduleva, Ekaterine

AU - Murtazalieva, Patimat

AU - Titov, Vladislav

AU - Malashicheva, Anna

AU - Shishkova, Anastasya

AU - Semenova, Daria

AU - Irtyuga, Olga

AU - Isakov, Dmitry

AU - Moiseeva, Olga

AU - Golovkin, Alexey

N1 - Kudryavtsev I, Serebriakova M, Zhiduleva E, Murtazalieva P, Titov V, Malashicheva A, Shishkova A, Semenova D, Irtyuga O, Isakov D, Mitrofanova L, Moiseeva O and Golovkin A (2019) CD73 Rather Than CD39 Is Mainly Involved in Controlling Purinergic Signaling in Calcified Aortic Valve Disease. Front. Genet. 10:604. doi: 10.3389/fgene.2019.00604

PY - 2019/7/25

Y1 - 2019/7/25

N2 - The study aimed to compare composition of peripheral blood T-cell subsets and assess their surface expression of CD39 and CD73 ectonucleotidases in patients with severe and moderate aortic stenosis (AS) as well as to evaluate involvement of T-cell-mediated immune processes in valve calcification. The study was performed with 38 patients suffering from severe calcified aortic stenosis (SAS), 33 patients with MAS, and 30 apparently healthy volunteers (HVs). The relative distribution and percentage of T-cell subsets expressing CD39 and CD73 were evaluated by flow cytometry. T helper (Th) and cytotoxic T-cell subsets (Tcyt) were identified by using CD3, CD4, and CD8 antibodies. Regulatory T cells (Tregs) were characterized by the expression of CD3, CD4, and high IL-2R alpha chain (CD25high) levels. CD45R0 and CD62L were used to assess differentiation stage of Th, Tcyt, and Treg subsets. It was found that MAS and SAS patients differed in terms of relative distribution of Tcyt and absolute number of Treg. Moreover, the absolute number of Tcyt and terminally differentiated CD45RA-positive effector T-cells (TEMRA) subset was significantly higher in SAS vs. MAS patients and HVs. However, the absolute and relative number of naïve Th and the absolute number of Treg were significantly higher in MAS vs. SAS patients; the relative number of naïve Tregs was significantly (p < 0.01) decreased in SAS patients. It was shown that CD73 expression was significantly higher in SAS vs. MAS patients noted in all EM, CM, TEMRA, and naïve Th cell subsets. However, only the latter were significantly increased (p = 0.003) in patients compared with HVs. SAS vs. MAS patients were noted to have significantly higher percentage of CD73+ EM Tcyt (p = 0.006) and CD73+ CM Tcyt (p = 0.002). The expression of CD73 in patients significantly differed in all three Treg populations such as EM (p = 0.049), CM (p = 0.044), and naïve (p < 0.001). No significant differences in CD39 expression level was found in MAS and SAS patients compared with the HV group. Overall, the data obtained demonstrated that purinergic signaling was involved in the pathogenesis of aortic stenosis and calcification potentially acting via various cell types, wherein among enzymes, degrading extracellular ATP CD73 rather than CD39 played a prominent role.

AB - The study aimed to compare composition of peripheral blood T-cell subsets and assess their surface expression of CD39 and CD73 ectonucleotidases in patients with severe and moderate aortic stenosis (AS) as well as to evaluate involvement of T-cell-mediated immune processes in valve calcification. The study was performed with 38 patients suffering from severe calcified aortic stenosis (SAS), 33 patients with MAS, and 30 apparently healthy volunteers (HVs). The relative distribution and percentage of T-cell subsets expressing CD39 and CD73 were evaluated by flow cytometry. T helper (Th) and cytotoxic T-cell subsets (Tcyt) were identified by using CD3, CD4, and CD8 antibodies. Regulatory T cells (Tregs) were characterized by the expression of CD3, CD4, and high IL-2R alpha chain (CD25high) levels. CD45R0 and CD62L were used to assess differentiation stage of Th, Tcyt, and Treg subsets. It was found that MAS and SAS patients differed in terms of relative distribution of Tcyt and absolute number of Treg. Moreover, the absolute number of Tcyt and terminally differentiated CD45RA-positive effector T-cells (TEMRA) subset was significantly higher in SAS vs. MAS patients and HVs. However, the absolute and relative number of naïve Th and the absolute number of Treg were significantly higher in MAS vs. SAS patients; the relative number of naïve Tregs was significantly (p < 0.01) decreased in SAS patients. It was shown that CD73 expression was significantly higher in SAS vs. MAS patients noted in all EM, CM, TEMRA, and naïve Th cell subsets. However, only the latter were significantly increased (p = 0.003) in patients compared with HVs. SAS vs. MAS patients were noted to have significantly higher percentage of CD73+ EM Tcyt (p = 0.006) and CD73+ CM Tcyt (p = 0.002). The expression of CD73 in patients significantly differed in all three Treg populations such as EM (p = 0.049), CM (p = 0.044), and naïve (p < 0.001). No significant differences in CD39 expression level was found in MAS and SAS patients compared with the HV group. Overall, the data obtained demonstrated that purinergic signaling was involved in the pathogenesis of aortic stenosis and calcification potentially acting via various cell types, wherein among enzymes, degrading extracellular ATP CD73 rather than CD39 played a prominent role.

KW - Calcification

KW - Calcified aortic stenosis

KW - CD39 and CD73 expression

KW - Purinergic signaling

KW - T-Cells (or lymphocytes)

KW - calcified aortic stenos T-cells (or lymphocytes)

KW - EXTRACELLULAR ATP

KW - purinergic signaling

KW - ACTIVATION

KW - ADENOSINE

KW - RECEPTOR

KW - TREG CELLS

KW - REGULATORY T-CELLS

KW - TRIPHOSPHATE

KW - GENERATION

KW - calcification

KW - DIFFERENTIATION

KW - EXPRESSION

UR - http://www.scopus.com/inward/record.url?scp=85069051372&partnerID=8YFLogxK

U2 - 10.3389/fgene.2019.00604

DO - 10.3389/fgene.2019.00604

M3 - Comment/debate

AN - SCOPUS:85069051372

VL - 10

JO - Frontiers in Genetics

JF - Frontiers in Genetics

SN - 1664-8021

M1 - 604

ER -