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Updated: Dec 10, 2025
A Rabbit Model of Durable Transgene Expression in Jugular Vein to Common Carotid Artery Interposition Grafts
Published on: September 10, 2018
Targeted gene expression analysis of human deep veins
Maxim E Shaydakov1, Jose A Diaz2, Anthony J Comerota3
1Conrad Jobst Research Vascular Laboratories, University of Michigan Medical School, Ann Arbor, Mich; Jobst Vascular Institute, ProMedica Toledo Hospital, Toledo, Ohio; Department of Surgery, Central Michigan University College of Medicine, Saginaw, Mich.
The human deep vein valve cusps show distinct molecular profiles, with higher expression of both prothrombotic and antithrombotic genes compared to the vein wall. This suggests unique biological properties influencing deep vein thrombosis (DVT) risk.
Area of Science:
- Vascular Biology
- Molecular Medicine
- Venous Thromboembolism
Background:
- Thrombosis and hemostasis research has primarily focused on arteries, with limited investigation into the human deep venous system.
- Understanding the molecular mechanisms within normal human deep veins is crucial for elucidating deep vein thrombosis (DVT) pathogenesis.
Purpose of the Study:
- To evaluate the expression of prothrombotic and antithrombotic genes in normal human deep veins of the lower extremities.
- To compare gene and protein expression between different segments of the deep vein, including the valve cusp and vein wall.
Main Methods:
- Human deep vein segments were prospectively collected and divided into four zones: postvalve vein wall, valve cusp, prevalve vein wall, and vein wall within the valve cusp.
- Real-time quantitative polymerase chain reaction (qPCR) was used to quantify messenger RNA (mRNA) for key coagulation, fibrinolysis, and inflammation genes.
- Protein expression was assessed using Western blot assays, and proteomic differences were investigated via mass spectrometry.
Main Results:
- The valve cusp showed significant upregulation of antithrombotic (e.g., PROCR, THBD), prothrombotic (e.g., VWF), and proinflammatory (e.g., SELP, ICAM1) genes compared to the vein wall.
- PROCR and THBD were highly upregulated in the valve cusp at the mRNA level.
- Protein analysis confirmed upregulation of PROCR, SERPINE1, and SELP in the valve cusp, with substantial proteomic differences observed between zones.
Conclusions:
- The valve cusp exhibits distinct biological properties compared to the surrounding vein wall, with potentially lower thrombogenicity and higher interaction potential with white blood cells.
- These findings highlight significant, previously unrecognized proteomic differences within normal deep veins.
- Understanding these molecular differences is essential for developing new hypotheses and therapeutic strategies for DVT.
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