VenaFlux Solutions mimic human blood vessels

The circulatory system contains many different types of blood vessels which delivers blood cells, nutrients, oxygen, carbon dioxide and hormones to all parts of the body.  Blood vessels play a huge role in many medical conditions.  Some examples include:  

  • Thrombosis - blockage or closing of a blood vessel from a thrombus (blood clot) can lead to ischaemia (insufficient blood supply).

  • Inflammation of the vessel wall is called vasculitis and is usually caused by leukocyte migration and resultant damage.  This is often due to autoimmune disorders or infection.  

  • Atherosclerosis - the narrowing of an artery due to the build-up of plaque (fatty deposits) - is one of the most common cardiovasular diseases, which can lead to one of many conditions including stroke or coronary artery disease.

 

THROMBOSIS

There are different types of blood clots.  A blood clot in the vein (usually leg or pelvis) is known as Deep Vein Thrombosis (DVT) and a clot that travels to the lungs is known as a Pulmonary Embolism (PE).  Together, these are known as Venous ThromboEmbolisms (VTE).  

The body uses platelets (thrombocytes) and fibrin to form a blood clot.  This usually occurs when there is an injury to a blood vessel and the formation of a blood clot is the body's way of preventing blood loss.  However, even when there is no injury to a blood vessel, blood clots may form and this is the basis of a huge area of research - understanding why and how it may be controlled.  

Platelet adhesion, aggregation and thrombi formation is an area of research which must be conducted under shear flow conditions.  

Platelet adhesion, aggregation, thrombi formation

What is shear flow?

Shear stress is the tangential force of the flowing blood on the endothelial surface of the blood vessel.  It is important to study platelet adhesion, aggregation and thrombi formation under shear flow conditions because increased shear conditions have been shown to activate platelets, alter the cellular localization of proteins such as tissue factor (TF) and TF pathway inhibitor, and regulate gene production, [1]:

"Thrombosis occurs in a dynamic rheological field where flow conditions regulate the transport of coagulation factors, inhibitors, and cells. Hemodynamic forces regulate not only the predilection of specific anatomic sites to thrombosis but strongly influence the biochemical makeup of thrombi and the reaction pathways involved in thrombus formation."

References

  1. James J. Hathcock. Flow Effects on Coagulation and Thrombosis.  Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1729–1737.  https://doi.org/10.1161/01.ATV.0000229658.76797.30

  2. Alkhamis TM, Beissinger RL, Chediak JR. Red blood cell effect on platelet adhesion and aggregation in low-stress shear flow. Myth or fact? ASAIO Transactions. 1988 Jul-Sep;34(3):868-873.

 

INFLAMMATION

The traditional three-step leukocyte adhesion cascade involves cell rolling, cell adhesion and cell migration and transmigration.

1.  Cell Rolling:  Selectin-mediated rolling.  Selectins are a family of single-chain transmembrane glycoproteins, expressed on the surface of leukocytes, platelets and activated endothelial cells.  E-selectin, also known as CD62E, is a cell adhesion molecule expressed only on endothelial cells activated by cytokines.  E-selectin recognizes and binds with low affinity to sialylated carbohydrates present on the surface proteins of certain leukocytes, causing the cells to roll along the endothelial surface of the blood vessel, as temporary interactions with exceptionally high on- and off-rates are
established.

Cell-Ligand / Cell-Protein Rolling

2.  Cell Adhesion:  Chemokine-triggered activation and integrin-dependent arrest.  As the inflammatory response progresses, chemokines released by injured tissue enter the blood vessels and activate the rolling leukocytes, which are now able to tightly bind to the endothelial surface, an essential step prior to transmigration towards the inflamed tissue.  Chemokines cause surface integrins to switch from a low-affinity state to a high-affinity state. In the activated state, integrins bind tightly to complementary receptors expressed on endothelial cells.  This promotes the firm adhesion of the leukocytes through integrin-mediated binding, such as VLA-4 that binds to VCAM-1, or LFA-1 to ICAM-1.

3.  Cell Migration & Transmigration:  Intraluminal crawling and paracellular and transcellular migration.

Cell-Ligand / Cell-Protein Adhesion

 

ATHEROSCLEROSIS

The narrowing of an artery due to the build-up of plaque (fatty deposits) - is one of the most common cardiovasular diseases, which can lead to one of many conditions including stroke or coronary artery disease.

Atherosclerosis

 

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