Morphometric and Nanomechanical Features of Platelets from Women with Early Pregnancy Loss Provide New Evidence of the Impact of Inherited Thrombophilia
Pregnancy is associated with hypercoagulation states and increased thrombotic risk, especially in women with thrombophilia. We combine atomic force microscopy (AFM) and flow cytometry to examine the morphology and nanomechanics of platelets derived from women with early pregnancy loss (EPL) and cont...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/15/7778 |
| _version_ | 1797525583172730880 |
|---|---|
| author | Tonya Andreeva Regina Komsa-Penkova Ariana Langari Sashka Krumova Georgi Golemanov Galya B. Georgieva Stefka G. Taneva Ina Giosheva Nikolina Mihaylova Andrey Tchorbanov Svetla Todinova |
| author_facet | Tonya Andreeva Regina Komsa-Penkova Ariana Langari Sashka Krumova Georgi Golemanov Galya B. Georgieva Stefka G. Taneva Ina Giosheva Nikolina Mihaylova Andrey Tchorbanov Svetla Todinova |
| author_sort | Tonya Andreeva |
| collection | DOAJ |
| description | Pregnancy is associated with hypercoagulation states and increased thrombotic risk, especially in women with thrombophilia. We combine atomic force microscopy (AFM) and flow cytometry to examine the morphology and nanomechanics of platelets derived from women with early pregnancy loss (EPL) and control pregnant (CP) and non-pregnant (CNP) women. Both control groups exhibit similar morphometric parameters (height and surface roughness) and membrane stiffness of platelets. EPL patients’ platelets, on the other hand, are more activated than the control groups, with prominent cytoskeletal rearrangement. In particular, reduced membrane roughness (22.9 ± 6 nm vs. 39.1 ± 8 nm) (<i>p</i> < 0.05) and height (692 ± 128 nm vs. 1090 ± 131 nm) (<i>p</i> < 0.05), strong alteration in the membrane Young modulus, increased production of platelets’ microparticles, and higher expression of procoagulant surface markers, as well as increased occurrence of thrombophilia (<i>FVL</i>, <i>FII20210A</i>, <i>PLA1/A2</i>, <i>MTHFR</i> <i>C677T</i> or 4G/5G <i>PAI-1</i>) polymorphisms were found. We suggest that the carriage of thrombophilic mutations triggers structural and nanomechanical abnormalities in platelets, resulting in their increased activation. The activation state of platelets can be well characterized by AFM, and the morphometric and nanomechanical characteristics might serve as a new criterion for evaluation of the cause of miscarriage and offer the prospect of an innovative approach serving for diagnostic purposes. |
| first_indexed | 2024-03-10T09:15:55Z |
| format | Article |
| id | doaj.art-6d0cc8e37560469f9825351a8ab3708e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:15:55Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6d0cc8e37560469f9825351a8ab3708e2023-11-22T05:38:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012215777810.3390/ijms22157778Morphometric and Nanomechanical Features of Platelets from Women with Early Pregnancy Loss Provide New Evidence of the Impact of Inherited ThrombophiliaTonya Andreeva0Regina Komsa-Penkova1Ariana Langari2Sashka Krumova3Georgi Golemanov4Galya B. Georgieva5Stefka G. Taneva6Ina Giosheva7Nikolina Mihaylova8Andrey Tchorbanov9Svetla Todinova10Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. Georgi Bonchev, Str. Bl. 21, 1113 Sofia, BulgariaDepartment of Biochemistry, Medical University, 1 St. Kliment Ohridski Str., 5800 Pleven, BulgariaInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. Georgi Bonchev, Str. Bl. 21, 1113 Sofia, BulgariaInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. Georgi Bonchev, Str. Bl. 21, 1113 Sofia, BulgariaDepartment of Biochemistry, Medical University, 1 St. Kliment Ohridski Str., 5800 Pleven, BulgariaDepartment of Biochemistry, Medical University, 1 St. Kliment Ohridski Str., 5800 Pleven, BulgariaInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. Georgi Bonchev, Str. Bl. 21, 1113 Sofia, BulgariaInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. Georgi Bonchev, Str. Bl. 21, 1113 Sofia, BulgariaStefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Acad. Georgi Bonchev, Str. Bl. 26, 1113 Sofia, BulgariaStefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Acad. Georgi Bonchev, Str. Bl. 26, 1113 Sofia, BulgariaInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. Georgi Bonchev, Str. Bl. 21, 1113 Sofia, BulgariaPregnancy is associated with hypercoagulation states and increased thrombotic risk, especially in women with thrombophilia. We combine atomic force microscopy (AFM) and flow cytometry to examine the morphology and nanomechanics of platelets derived from women with early pregnancy loss (EPL) and control pregnant (CP) and non-pregnant (CNP) women. Both control groups exhibit similar morphometric parameters (height and surface roughness) and membrane stiffness of platelets. EPL patients’ platelets, on the other hand, are more activated than the control groups, with prominent cytoskeletal rearrangement. In particular, reduced membrane roughness (22.9 ± 6 nm vs. 39.1 ± 8 nm) (<i>p</i> < 0.05) and height (692 ± 128 nm vs. 1090 ± 131 nm) (<i>p</i> < 0.05), strong alteration in the membrane Young modulus, increased production of platelets’ microparticles, and higher expression of procoagulant surface markers, as well as increased occurrence of thrombophilia (<i>FVL</i>, <i>FII20210A</i>, <i>PLA1/A2</i>, <i>MTHFR</i> <i>C677T</i> or 4G/5G <i>PAI-1</i>) polymorphisms were found. We suggest that the carriage of thrombophilic mutations triggers structural and nanomechanical abnormalities in platelets, resulting in their increased activation. The activation state of platelets can be well characterized by AFM, and the morphometric and nanomechanical characteristics might serve as a new criterion for evaluation of the cause of miscarriage and offer the prospect of an innovative approach serving for diagnostic purposes.https://www.mdpi.com/1422-0067/22/15/7778plateletsearly pregnancy lossatomic force microscopypolymorphisms in thrombophilia genesflow cytometry |
| spellingShingle | Tonya Andreeva Regina Komsa-Penkova Ariana Langari Sashka Krumova Georgi Golemanov Galya B. Georgieva Stefka G. Taneva Ina Giosheva Nikolina Mihaylova Andrey Tchorbanov Svetla Todinova Morphometric and Nanomechanical Features of Platelets from Women with Early Pregnancy Loss Provide New Evidence of the Impact of Inherited Thrombophilia International Journal of Molecular Sciences platelets early pregnancy loss atomic force microscopy polymorphisms in thrombophilia genes flow cytometry |
| title | Morphometric and Nanomechanical Features of Platelets from Women with Early Pregnancy Loss Provide New Evidence of the Impact of Inherited Thrombophilia |
| title_full | Morphometric and Nanomechanical Features of Platelets from Women with Early Pregnancy Loss Provide New Evidence of the Impact of Inherited Thrombophilia |
| title_fullStr | Morphometric and Nanomechanical Features of Platelets from Women with Early Pregnancy Loss Provide New Evidence of the Impact of Inherited Thrombophilia |
| title_full_unstemmed | Morphometric and Nanomechanical Features of Platelets from Women with Early Pregnancy Loss Provide New Evidence of the Impact of Inherited Thrombophilia |
| title_short | Morphometric and Nanomechanical Features of Platelets from Women with Early Pregnancy Loss Provide New Evidence of the Impact of Inherited Thrombophilia |
| title_sort | morphometric and nanomechanical features of platelets from women with early pregnancy loss provide new evidence of the impact of inherited thrombophilia |
| topic | platelets early pregnancy loss atomic force microscopy polymorphisms in thrombophilia genes flow cytometry |
| url | https://www.mdpi.com/1422-0067/22/15/7778 |
| work_keys_str_mv | AT tonyaandreeva morphometricandnanomechanicalfeaturesofplateletsfromwomenwithearlypregnancylossprovidenewevidenceoftheimpactofinheritedthrombophilia AT reginakomsapenkova morphometricandnanomechanicalfeaturesofplateletsfromwomenwithearlypregnancylossprovidenewevidenceoftheimpactofinheritedthrombophilia AT arianalangari morphometricandnanomechanicalfeaturesofplateletsfromwomenwithearlypregnancylossprovidenewevidenceoftheimpactofinheritedthrombophilia AT sashkakrumova morphometricandnanomechanicalfeaturesofplateletsfromwomenwithearlypregnancylossprovidenewevidenceoftheimpactofinheritedthrombophilia AT georgigolemanov morphometricandnanomechanicalfeaturesofplateletsfromwomenwithearlypregnancylossprovidenewevidenceoftheimpactofinheritedthrombophilia AT galyabgeorgieva morphometricandnanomechanicalfeaturesofplateletsfromwomenwithearlypregnancylossprovidenewevidenceoftheimpactofinheritedthrombophilia AT stefkagtaneva morphometricandnanomechanicalfeaturesofplateletsfromwomenwithearlypregnancylossprovidenewevidenceoftheimpactofinheritedthrombophilia AT inagiosheva morphometricandnanomechanicalfeaturesofplateletsfromwomenwithearlypregnancylossprovidenewevidenceoftheimpactofinheritedthrombophilia AT nikolinamihaylova morphometricandnanomechanicalfeaturesofplateletsfromwomenwithearlypregnancylossprovidenewevidenceoftheimpactofinheritedthrombophilia AT andreytchorbanov morphometricandnanomechanicalfeaturesofplateletsfromwomenwithearlypregnancylossprovidenewevidenceoftheimpactofinheritedthrombophilia AT svetlatodinova morphometricandnanomechanicalfeaturesofplateletsfromwomenwithearlypregnancylossprovidenewevidenceoftheimpactofinheritedthrombophilia |