TY - JOUR
T1 - Small extracellular vesicles from pregnant women with maternal supraphysiological hypercholesterolemia impair endothelial cell function in vitro
AU - Contreras-Duarte, Susana
AU - Escalona-Rivano, Rodrigo
AU - Cantin, Claudette
AU - Valdivia, Pascuala
AU - Zapata, David
AU - Carvajal, Lorena
AU - Brito, Roberto
AU - Cerda, Álvaro
AU - Illanes, Sebastián
AU - Gutiérrez, Jaime
AU - Leiva, Andrea
N1 - Funding Information:
We thank the personnel at the Clínica Dávila labor ward for their support in supplying placentas, to Amparo Pacheco for technical assistance, to Centro de Biología Celular y Biomedicina (CEBICEM) for the access to the ultracentrifuge and to Dr. Cristian Carvajal from Department of Endocrinology UC for the access to the ultracentrifuge and NTA. This work was supported by programs from the Agencia Nacional de Investigacion y Desarrollo, Chile (ANID): Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT 1221362, 1190250 and 1230527), Subvencion a la Instalacion en la Academia SA77210098 and Basal Funding for Scientific and Technological Center of Excelence, IMPACT, FB210024. All the authors have read the journal's policy on disclosure of potential conflicts of interest. All the authors have disclosed any financial or personal relationship with organizations that could potentially be perceived as influencing the described research.
Funding Information:
We thank the personnel at the Clínica Dávila labor ward for their support in supplying placentas, to Amparo Pacheco for technical assistance, to Centro de Biología Celular y Biomedicina (CEBICEM) for the access to the ultracentrifuge and to Dr. Cristian Carvajal from Department of Endocrinology UC for the access to the ultracentrifuge and NTA. This work was supported by programs from the Agencia Nacional de Investigacion y Desarrollo, Chile (ANID): Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT 1221362, 1190250 and 1230527), Subvencion a la Instalacion en la Academia SA77210098 and Basal Funding for Scientific and Technological Center of Excelence, IMPACT, FB210024. All the authors have read the journal's policy on disclosure of potential conflicts of interest. All the authors have disclosed any financial or personal relationship with organizations that could potentially be perceived as influencing the described research.
Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2023/6
Y1 - 2023/6
N2 - Maternal physiological hypercholesterolemia MPH, maternal total cholesterol (TC) levels at term of pregnancy ≤280 mg/dL) occurs to assure fetal development. Maternal supraphysiological hypercholesterolemia (MSPH, TC levels >280 mg/dL) is a pathological condition associated with maternal, placental, and fetal endothelial dysfunction and early neonatal atherosclerosis development. Small extracellular vesicles (sEVs) are delivered to the extracellular space by different cells, where they modulate cell functions by transporting active signaling molecules, including proteins and miRNA. Aim: To determine whether sEVs from MSPH women could alter the function of endothelial cells (angiogenesis, endothelial activation and nitric oxide synthesis capacity). Methods: This study included 24 Chilean women (12 MPH and 12 MSPH). sEVs were isolated from maternal plasma and characterized by sEV markers (CD9, Alix and HSP70), nanoparticle tracking analysis, transmission electron microscopy, and protein and cholesterol content. The endothelial cell line HMEC-1 was used to determine the uptake of labeled sEVs and the effects of sEVs on cell viability, endothelial tube formation, endothelial cell activation, and endothelial nitric oxide expression and function. Results: In MSPH women, the plasma concentration of sEVs was increased compared to that in MPH women. MSPH-sEVs were highly taken up by HMEC-1 cells and reduced angiogenic capacity and the expression and activity of eNOS without changing cell viability or endothelial activation compared to MPH-sEVs. Conclusion: sEVs from MSPH women impair angiogenesis and nitric oxide synthesis in endothelial cells, which could contribute to MSPH-associated endothelial dysfunction.
AB - Maternal physiological hypercholesterolemia MPH, maternal total cholesterol (TC) levels at term of pregnancy ≤280 mg/dL) occurs to assure fetal development. Maternal supraphysiological hypercholesterolemia (MSPH, TC levels >280 mg/dL) is a pathological condition associated with maternal, placental, and fetal endothelial dysfunction and early neonatal atherosclerosis development. Small extracellular vesicles (sEVs) are delivered to the extracellular space by different cells, where they modulate cell functions by transporting active signaling molecules, including proteins and miRNA. Aim: To determine whether sEVs from MSPH women could alter the function of endothelial cells (angiogenesis, endothelial activation and nitric oxide synthesis capacity). Methods: This study included 24 Chilean women (12 MPH and 12 MSPH). sEVs were isolated from maternal plasma and characterized by sEV markers (CD9, Alix and HSP70), nanoparticle tracking analysis, transmission electron microscopy, and protein and cholesterol content. The endothelial cell line HMEC-1 was used to determine the uptake of labeled sEVs and the effects of sEVs on cell viability, endothelial tube formation, endothelial cell activation, and endothelial nitric oxide expression and function. Results: In MSPH women, the plasma concentration of sEVs was increased compared to that in MPH women. MSPH-sEVs were highly taken up by HMEC-1 cells and reduced angiogenic capacity and the expression and activity of eNOS without changing cell viability or endothelial activation compared to MPH-sEVs. Conclusion: sEVs from MSPH women impair angiogenesis and nitric oxide synthesis in endothelial cells, which could contribute to MSPH-associated endothelial dysfunction.
KW - Angiogenesis
KW - Cholesterol
KW - Endothelial function
KW - Nitric oxide
KW - Pregnancy
KW - Small extracellular vesicles
UR - http://www.scopus.com/inward/record.url?scp=85158023695&partnerID=8YFLogxK
U2 - 10.1016/j.vph.2023.107174
DO - 10.1016/j.vph.2023.107174
M3 - Article
C2 - 37105374
AN - SCOPUS:85158023695
SN - 1537-1891
VL - 150
JO - Vascular Pharmacology
JF - Vascular Pharmacology
M1 - 107174
ER -