Therefore, the reported clinical outcome of septic patients receiving statin therapy can at least be partially associated with T cell-ICAM binding activities.
Cardiovascular—Platelet adhesion is an essential function in response to vascular injury and is generally viewed as the first step during which single platelets bind through specific membrane receptors to cellular and extracellular matrix constituents of the vessel wall and tissues. This response initiates thrombus formation that arrests hemorrhage and permits wound healing.
Pathological conditions that cause vascular alterations and blood-flow disturbances may turn this beneficial process into a disease mechanism that results in arterial occlusion, most frequently in atherosclerotic vessels of the heart and brain. Besides their relevant role in hemostasis and thrombosis, platelet-adhesive properties are central to a variety of pathophysiological processes that extend from inflammation to immune-mediated host defenses and pathogenic mechanisms as well as cancer metastasis.
All of these activities depend on the ability of platelets to circulate in the blood as sentinels of vascular integrity, adhere where alterations are detected, and signal the abnormality to other platelets and blood cells. In this respect, therefore, platelet adhesion to vascular wall structures, to one another (aggregation), or to other blood cells represent different aspects of the same fundamental biological process.
Detailed studies by many investigators, Dermot Kenny and Ger Meade of the Royal College of Surgeons in Ireland (RCSI) in Dublin among them, have been aimed at dissecting the complexity of these functions, and the results obtained now permit an attempt to integrate all the available information into a picture that highlights the balanced diversity and synergy of distinct platelet adhesive interactions.
VenaFlux allowed researchers at RCSI to mimic blood flow and monitor thrombus formation. Rolling/adhesion of platelets on Vena8 biochips, coated with adhesion molecule vwf, occurs at lower shear stress (4 and 40 dyne/cm2), whereas at higher shear stress (60 and 120 dyne/cm2) platelet thrombus formation appears. A threshold limit of approximately 60 dyne/cm2 is required for thrombus formation, conditions that occur in microcirculation.
Oncology—Although the spread of tumors is poorly understood, mainly due to the inavailability of an appropriate animal model, recent developments have provided insight into the complex cascade of specific events required to establish a metastatic deposit. As knowledge unfolds, cancer adjuvant therapy will be directed increasingly toward the prevention of the devastation caused by metastases.
Blood flow has traditionally been accepted as the only determinant of the site of a metastatic deposit. In metastasis, cells are spread from a primary tumor to a distant site, where they arrest and grow to form a secondary tumor. Interaction with endothelial cells at the initial and later stages of the metastatic cascade is mandatory for the passage of tumor cells into vessels at the primary site and exit from vessels at the metastatic site.
Several factors, including certain members of the immunoglobulin and selectin families, facilitate adherence of tumor cells to endothelium. Platelet-fibrin thrombi influence the arrest of tumor cells. Chemotactic factors released by endothelial cells enhance tumor-cell mobility.
VenaFlux can visualize and quantify the movement of tumor cells and their interactions with the endothelium as they travel through metastatic pathways within the body to arrest at secondary sites. It can also be used to quantify the morphology and functional capacity of tumor microvasculature, as well as the timing and dynamic effects of drugs targeted to disrupt tumor vasculaturization.
With the development of new fluorescent probes and reporter genes, VenaFlux has the potential to provide evidence of the timing and location of metabolic processes within the metastatic cascade that may serve as specific targets for the treatment of cancer.