TY - JOUR

T1 - Extracellular vesicles of the liver fluke Opisthorchis felineus stimulate the angiogenesis of human umbilical vein endothelial cells

AU - Ponomarev, Dmitry V

AU - Lishai, Ekaterina A

AU - Kovner, Anna V

AU - Kharkova, Maria V

AU - Zaparina, Oxana

AU - Kapuschak, Yaroslav K

AU - Mordvinov, Viatcheslav A

AU - Pakharukova, Maria Y

N1 - We are thankful to Natalya V. Gubanova for the valuable technical assistance. We are also very grateful to Pavel P. Laktionov for help with reagents. The microscopic analysis was conducted at the Microscopy Center of the ICG SB RAS (No. FWNR-2022-0021; FWNR-2022-0007). The English language was corrected by shevchuk-editing.com. Real-time PCR analysis was conducted at the Center for Collective Use “Proteomic Analysis”, supported by funding from the Ministry of Science and Higher Education of the Russian Federation (agreement No. 075-15-2021-691). © 2023 The Authors.

PY - 2023/1

Y1 - 2023/1

N2 - The liver fluke Opisthorchis felineus is a clinically important food-borne parasite of humans. Infection with O. felineus in mammals is associated with liver morbidities such as periductal fibrosis, bile duct neoplasia, and chronic inflammation. Previously we have shown that excretory-secretory products (ESP) can stimulate the healing of skin wounds in mice, which may be due to stimulated angiogenesis and extracellular matrix remodeling. However, there are no studies analyzing the angiogenic character of O. felineus, and its effects on angiogenesis, vascularity, and vascular endothelium. The aim of this study was to evaluate the capacity of ESP and extracellular vesicles (EVs) of O. felineus to stimulate angiogenesis and the formation of pseudo-capillaries in vitro. We also aimed at the assessment of the angiogenesis during the infection in vivo, and estimation of the endothelial cell type abundances from heterogeneous bulk liver transcriptome between uninfected and infected animals with single-cell information. The study revealed significant alterations in vascularity in the hamster liver and significant involvement of portal endothelial cells at the transcriptome level. We also demonstrated that the ESP and EVs of O. felineus have the capacity to stimulate the formation of pseudo-capillaries in vitro. Both ESP and EVs appeared to have similar effects on all four parameters, increasing node formation and total master segments length, and significantly decreasing total isolated branches length and number of isolated segments of pseudo-capillaries. The liver flukes manipulate the host's angiogenic response, a fact that has been related to the pathogenesis caused by these parasites. Understanding these pathogenic mechanisms may uncover new therapeutic targets to relieve or prevent the most severe complications of opisthorchiasis.

AB - The liver fluke Opisthorchis felineus is a clinically important food-borne parasite of humans. Infection with O. felineus in mammals is associated with liver morbidities such as periductal fibrosis, bile duct neoplasia, and chronic inflammation. Previously we have shown that excretory-secretory products (ESP) can stimulate the healing of skin wounds in mice, which may be due to stimulated angiogenesis and extracellular matrix remodeling. However, there are no studies analyzing the angiogenic character of O. felineus, and its effects on angiogenesis, vascularity, and vascular endothelium. The aim of this study was to evaluate the capacity of ESP and extracellular vesicles (EVs) of O. felineus to stimulate angiogenesis and the formation of pseudo-capillaries in vitro. We also aimed at the assessment of the angiogenesis during the infection in vivo, and estimation of the endothelial cell type abundances from heterogeneous bulk liver transcriptome between uninfected and infected animals with single-cell information. The study revealed significant alterations in vascularity in the hamster liver and significant involvement of portal endothelial cells at the transcriptome level. We also demonstrated that the ESP and EVs of O. felineus have the capacity to stimulate the formation of pseudo-capillaries in vitro. Both ESP and EVs appeared to have similar effects on all four parameters, increasing node formation and total master segments length, and significantly decreasing total isolated branches length and number of isolated segments of pseudo-capillaries. The liver flukes manipulate the host's angiogenic response, a fact that has been related to the pathogenesis caused by these parasites. Understanding these pathogenic mechanisms may uncover new therapeutic targets to relieve or prevent the most severe complications of opisthorchiasis.

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85178900299&origin=inward&txGid=add9d9ffca0326e3c2df38501731cb31

UR - https://www.mendeley.com/catalogue/c575cdef-9100-35b1-b047-412467486b5f/

U2 - 10.1016/j.crpvbd.2023.100153

DO - 10.1016/j.crpvbd.2023.100153

M3 - Article

C2 - 38045538

VL - 4

JO - Current research in parasitology & vector-borne diseases

JF - Current research in parasitology & vector-borne diseases

SN - 2667-114X

M1 - 100153

ER -