Quantitative and structural characteristics of mitochondrial DNA in varicose veins

Quantitative and structural characteristics of mitochondrial DNA in varicose veins Full article

Journal

Vascular Pharmacology

Output data

Year: 2022, Volume: 145, Article number : 107021, Pages count : DOI: 10.1016/j.vph.2022.107021

Tags

ddPCR; Mitochondrial DNA (mtDNA) copy number and deletions; Mitochondrial membrane potential; qPCR; Varicose veins

Authors

Smetanina M.A. ^1,2 , Oscorbin I.P. ^1,3 , Shadrina A.S. ⁴ , Sevost'ianova K.S. ^5,6 , Korolenya V.A. ^1,3 , Gavrilov K.A. ^5,6 , Shevela A.I. ^5,6 , Shirshova A.N. ¹ , Oskina N.A. ¹ , Zolotukhin I.A. ⁷ , Filipenko M.L. ^1,8

Affiliations

1	Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, 630090, Russian Federation
2	Department of Fundamental Medicine of V. Zelman Institute for the Medicine and Psychology, Novosibirsk State University, Novosibirsk, 630090, Russian Federation
3	Department of Natural Sciences, Novosibirsk State University, Novosibirsk, 630090, Russian Federation
4	Laboratory of Glycogenomics, Institute of Cytology and Genetics, Novosibirsk, 630090, Russian Federation
5	Center of New Medical Technologies, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, 630090, Russian Federation
6	Department of Surgical Diseases of V. Zelman Institute for the Medicine and Psychology, Novosibirsk State University, Novosibirsk, 630090, Russian Federation
7	Department of Faculty Surgery, Pirogov Russian National Research Medical University, Moscow, 117997, Russian Federation
8	Laboratory of Molecular Diagnostics Development, Department of Natural Sciences, Novosibirsk State University, Novosibirsk, 630090, Russian Federation

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. © 2022 Elsevier Inc.

Smetanina M.A. , Oscorbin I.P. , Shadrina A.S. , Sevost'ianova K.S. , Korolenya V.A. , Gavrilov K.A. , Shevela A.I. , Shirshova A.N. , Oskina N.A. , Zolotukhin I.A. , Filipenko M.L.
Quantitative and structural characteristics of mitochondrial DNA in varicose veins
Vascular Pharmacology. 2022. V.145. 107021 . DOI: 10.1016/j.vph.2022.107021 Scopus РИНЦ OpenAlex

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