Research output: Contribution to journal › Article › peer-review
Quantitative and structural characteristics of mitochondrial DNA in varicose veins. / Smetanina, Mariya A.; Oscorbin, Igor P.; Shadrina, Alexandra S. et al.
In: Vascular Pharmacology, Vol. 145, 107021, 08.2022.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Quantitative and structural characteristics of mitochondrial DNA in varicose veins
AU - Smetanina, Mariya A.
AU - Oscorbin, Igor P.
AU - Shadrina, Alexandra S.
AU - Sevost'ianova, Kseniya S.
AU - Korolenya, Valeria A.
AU - Gavrilov, Konstantin A.
AU - Shevela, Andrey I.
AU - Shirshova, Arina N.
AU - Oskina, Natalya A.
AU - Zolotukhin, Igor A.
AU - Filipenko, Maxim L.
N1 - Funding Information: The work on mtDNA genotyping in the whole vein segments was supported by the Russian Science Foundation [grant number 17-75-20223 ]; the work on mtDNA genotyping and fluorescent live-staining of mitochondria in the vein wall layers, was supported by the Russian Science Foundation [grant number 22-25-00832 ]. Publisher Copyright: © 2022 Elsevier Inc.
PY - 2022/8
Y1 - 2022/8
N2 - Objective: We examined quantitative (in terms of mtDNA/nuclear DNA) and structural (in terms of common deletions in the MT-ND4 gene region) characteristics of mitochondrial DNA (mtDNA) in varicose veins (VVs) and venous wall layers by comparing mitochondrial genome parameters, as well as mitochondrial function (in terms of mitochondrial membrane potential (MtMP)), in varicose vein (VV) vs. non-varicose vein (NV) tissue samples. Methods: We analyzed paired great saphenous vein samples (VV vs. NV segments from each patient left after venous surgery) harvested from patients with VVs. Relative mtDNA level and the proportion of no-deletion mtDNA were determined by a multiplex quantitative PCR (qPCR), confirming the latter with a more sensitive method – droplet digital PCR (ddPCR). Mitochondria's functional state in VVs was assessed using fluorescent (dependent on MtMP) live-staining of mitochondria in venous tissues. Results: Total mtDNA level was lower in VV than in NV samples (predominantly in the t. media layer). ddPCR analysis showed lower proportion of no-deletion mtDNA in VVs. Because of the decrease in relative MtMP in VVs, our results suggest a possible reduction of mitochondrial function in VVs. Conclusion: Quantitative and structural changes (copy number and integrity) of mtDNA are plausibly involved in VV pathogenesis. Future clinical studies implementing the mitochondrial targeting may be eventually fostered after auxiliary mechanistic studies.
AB - Objective: We examined quantitative (in terms of mtDNA/nuclear DNA) and structural (in terms of common deletions in the MT-ND4 gene region) characteristics of mitochondrial DNA (mtDNA) in varicose veins (VVs) and venous wall layers by comparing mitochondrial genome parameters, as well as mitochondrial function (in terms of mitochondrial membrane potential (MtMP)), in varicose vein (VV) vs. non-varicose vein (NV) tissue samples. Methods: We analyzed paired great saphenous vein samples (VV vs. NV segments from each patient left after venous surgery) harvested from patients with VVs. Relative mtDNA level and the proportion of no-deletion mtDNA were determined by a multiplex quantitative PCR (qPCR), confirming the latter with a more sensitive method – droplet digital PCR (ddPCR). Mitochondria's functional state in VVs was assessed using fluorescent (dependent on MtMP) live-staining of mitochondria in venous tissues. Results: Total mtDNA level was lower in VV than in NV samples (predominantly in the t. media layer). ddPCR analysis showed lower proportion of no-deletion mtDNA in VVs. Because of the decrease in relative MtMP in VVs, our results suggest a possible reduction of mitochondrial function in VVs. Conclusion: Quantitative and structural changes (copy number and integrity) of mtDNA are plausibly involved in VV pathogenesis. Future clinical studies implementing the mitochondrial targeting may be eventually fostered after auxiliary mechanistic studies.
KW - ddPCR
KW - Mitochondrial DNA (mtDNA) copy number and deletions
KW - Mitochondrial membrane potential
KW - qPCR
KW - Varicose veins
UR - http://www.scopus.com/inward/record.url?scp=85132429981&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/464ec87e-fc9f-354a-a123-c69b7d9a5ba1/
U2 - 10.1016/j.vph.2022.107021
DO - 10.1016/j.vph.2022.107021
M3 - Article
C2 - 35690235
AN - SCOPUS:85132429981
VL - 145
JO - Vascular Pharmacology
JF - Vascular Pharmacology
SN - 1537-1891
M1 - 107021
ER -
ID: 36428668