Seminario Biología Molecular Tercer Semestre Medicina Universidad Pontificia Bolivariana

1. LISSETH KARINA MARÍN RÍOS
3RD SEMESTER
UNIVERSIDAD PONTIFICIA BOLIVARIANA
2024

2. A venous thrombosis is a serious condition that
occurs when a blood clot forms in a vein,
typically in the legs, thighs, or pelvis. These clots
can block blood flow and cause swelling, pain,
and even break off and travel to the lungs,
leading to a life-threatening condition called
pulmonary embolism.
VENOUS THROMBUS
INTRODUCTION

3. Function:
Acts as both a pro-inflammatory cytokine and an anti-
inflammatory myokine (produced by muscle cells)
Production:
Primarily produced by immune cells like macrophages and T cells,
but also by other cell types like endothelial cells and fibroblasts
Effects:
Stimulates the production of acute phase proteins in the liver
during inflammation
Plays a role in fever and the acute phase response
Regulates various metabolic processes
IL-6
INTRODUCTION

4. Analyzing experimental
resolution of venous
thrombus is driven by IL-6-
mediated monocyte
actions.
GENERAL
OBJECTIVE

5. The objective of this experimental method is to investigate how
the protein composition of blood clots (thrombi), the inferior
vena cava (IVC), and specific immune cells (BMDMs and
RAW264.7) is influenced by exposure to IL-6 (an inflammatory
molecule) or Brefeldin A (an inhibitor of protein transport).
The objective of this method is to analyze the
structure, cellular composition, and components of
blood clots (thrombus) formed in the lower back
(retroperitoneal area) of mice.
METHODS
WESTERN BLOTS
HISTOLOGY

6. The objective of this experimental method is to
measure and analyze the levels of specific RNA
molecules within cells
METHODS
FLOW CITOMETRY
PCR
The objective of this experimental method is to isolate and
analyze specific types of immune cells from mice to
investigate how they are involved in the process of blood
clot formation or resolution

7. Following sham surgery
or stasis thrombosis, vein
wall lysate protein levels
Gel blots cropped from
different parts of the gel are
presented, with white line
separation. Protein levels of
intrathrombus.
Representative
photomicrographs at
40 × of WT (left, arrows
mark recanalization
channels) and IL-6−/−
RESULTS

8. Quantification of protein
levels relative to total
protein loading is shown
in the upper panels.
Protein levels of MMP9 and
Urokinase were assayed in the
BMDMs

9. DISCUSSION
From this series of experiments, we
have characterized the role of IL-6 in
two models of VT which replicate
clinical venous thrombosis; namely,
partial and complete blood stasis.
We found that IL6 gene deletion did
not affect thrombus formation,
contrary to data suggesting that anti-
IL-6 inhibition can impair
thrombogenesis
. Zhang, Y. (2020)
. Deatrick,K.B. (2011)
IL-6 has been shown to play a role in
thrombogenesis and resolution17,54,
but not as a key mediator of fibrinolysis
. Stouthard,J.M. (1996)
AUTHOR
What did they say?
AGREE OR
DESAGRREE

10. Conclusions
Interleukin-6 (IL-6) plays a crucial role in the resolution of venous thrombi:
The article demonstrates that IL-6 is produced by macrophages at the thrombus site.
IL-6 promotes the differentiation of monocytes to macrophages with a pro-resolving
phenotype. These pro-resolving macrophages phagocytize (ingest) dead cells and debris,
which facilitates dissolution of the thrombus.
Implications for the development of new therapies:
Strategies that modulate IL-6 signaling or that increase the activity of pro-resolving
macrophages could be useful in promoting thrombus dissolution and preventing thrombotic
complications.

11. * TVP: Trombosis venosa profunda EP: Embolisis Pulmonar
Referencias: Mayo Clinic Trombosis venosa profunda (TVP) [Internet]. 2022. Disponible en: https://www.mayoclinic.org/es/diseases-conditions/deep-vein-thrombosis/symptoms-causes/syc-20352557
National Heart, Lung, and Blood Institute. Venous thromboembolism [Internet]. Disponible en: https://www.nhlbi.nih.gov/health/venous-thromboembolism