How platelets safeguard vascular integrity

Abstract

Summary The haemostatic role of platelets was established in the 1880s by Bizzozero who observed their ability to adhere and aggregate at sites of vascular injury. It was only some 80 years later that the function of platelets in maintaining the structural integrity of intact blood vessels was reported by Danielli. Danielli noted that platelets help preserve the barrier function of endothelium during organ perfusion. Subsequent studies have demonstrated further that platelets are continuously needed to support intact mature blood vessels. More recently, platelets were shown to safeguard developing vessels, lymphatics, as well as the microvasculature at sites of leukocyte infiltration, including inflamed organs and tumours. Interestingly, from a mechanistic point of view, the supporting role of platelets in these various vessels does not necessarily involve the well-understood process of platelet plug formation but, rather, may rely on secretion of the various platelet granules and their many active components. The present review focuses on these nonconventional aspects of platelet biology and function by presenting situations in which platelets intervene to maintain vascular integrity and discusses possible mechanisms of their actions. We propose that modulating these newly described platelet functions may help treat haemorrhage as well as treat cancer by increasing the efficacy of drug delivery to tumours.

Apolipoprotein A‐I Modulates Atherosclerosis Through Lymphatic Vessel‐Dependent Mechanisms in Mice

“…Whereas an excess of platelet activation in blood circulation is often deleterious and is associated with clinically devastating outcomes in atherosclerosis, platelets are also known to support the semipermeable function of the blood vessel endothelium 69. In lymphatic physiology, they play a critical role in the development and maintenance of the lymphatic system.…”

Risk of bleeding and use of platelet transfusions in patients with hematologic malignancies: recurrent event analysis

“…Data were not available on documented infection for our analysis, and the impact of sepsis on risk of bleeding (and role of platelets) may differ from that of fever alone. 20 In the subsequent recurrent event analyses (analyses 2b and 2c), not all factors from analysis 2a reached statistical significance (treatment arm and sex were not significant in either model, and the interaction between previous day platelet count and bleeding episode was not significant in analysis 2c.) However, the effects of each factor were similar across all models (the hazard ratios for each model are shown in the Online Supplementary Appendix).…”

Platelets can enhance vascular permeability

“…1 In addition to their role in primary hemostasis, platelets also protect the vasculature against leakage. 2 Indeed, although basal levels of vascular permeability is necessary to allow the passage of small molecules, such as nutrients, ions, and water, the ultrastructural changes to the endothelium that accompany thrombocytopenia prompt vasculature leakage and can lead to edema or uncontrolled bleedings. [2][3][4][5][6] Further, induction of thrombocytopenia engenders hemorrhages localized at the site of inflammation during Arthus reaction, stroke, sunburn, and endotoxininduced lung inflammation, 7,8 pointing to a critical role of platelets in maintenance of blood vessels in inflammatory conditions.…”