Platelets in Pulmonary Vascular Physiology and Pathology

Abstract

Almost a trillion platelets pass through the pulmonary circulation every minute, yet little is known about how they support pulmonary physiology or contribute to the pathogenesis of lung diseases. When considering this conundrum, three questions jump out: Does platelet production in the lungs occur? Why does severe thrombocytopenia—which undercuts the principal physiological role of platelets to effect hemostasis—not lead to pulmonary hemorrhage? Why does atherothrombosis—which platelets initiate, maintain, and trigger is other critically important arterial beds—not develop in the pulmonary artery? The purpose of this review is to explore these and derivative questions by providing data within a conceptual framework that begins to organize a subject that is largely unassembled.

Diabetic Microvascular Disease and Pulmonary Fibrosis: The Contribution of Platelets and Systemic Inflammation

“…Pulmonary complications, while often subclinical in diabetic patients because of the lungs’ functional reserve, may become clinically important as patients subsequently develop chronic restrictive and obstructive pulmonary functional changes. Such changes would compromise ventilation and gas exchange, which together with endothelial dysfunction and excessive platelet activation may promote the induction of the fibrotic process [17,18,19]. Several studies identified a restrictive pattern in the lungs of diabetic patients that differed from smoking-induced lung pathology and was not correlated with confounding factors such as Body Mass Index (BMI), smoking, duration of the disease or HbA1c levels [10,20].…”

“…They contribute to redox imbalance through production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), pro-leak molecules, and recruitment of inflammatory cytokines and leukocytes to the damaged endothelium (Figure 1) [28,39,40,41,42,43]. The lungs are a significant source of megakaryocytes, generating platelets that contribute to basal barrier integrity of the alveolar capillaries and to pulmonary vascular repair [19,39]. …”

“…However, platelets also contribute to injury and to leukocyte recruitment and infiltration through their interaction with activated endothelial cells in a variety of pulmonary disorders [19,39,43,44,45]. Platelets store and secrete various cytokines, such as transforming growth factor beta (TGF-β) or platelet-derived growth factor (PDGF), and are implicated in the development of fibrosis and in various forms of idiopathic pulmonary fibrosis with platelet dysfunction or platelet granules abnormalities [19].…”

“…However, platelets also contribute to injury and to leukocyte recruitment and infiltration through their interaction with activated endothelial cells in a variety of pulmonary disorders [19,39,43,44,45]. Platelets store and secrete various cytokines, such as transforming growth factor beta (TGF-β) or platelet-derived growth factor (PDGF), and are implicated in the development of fibrosis and in various forms of idiopathic pulmonary fibrosis with platelet dysfunction or platelet granules abnormalities [19]. Platelet hyperreactivity in diabetic patients has been reported as early as 1965 and is associated with hyperglycemia, hyperlipidemia, inflammatory and oxidant states and increased glycation of surface membrane proteins, as well as higher calcium and lower cAMP levels that increase platelet sensitivity to agonists [37,46,47,48,49,50,51,52].…”

Avaliação da relação entre produção plaquetária e expressão de proteínas do sistema apoptótico plaquetário em diferentes graus de plaquetopenia da Trombocitopenia Imune (PTI)

“…As plaquetas desempenham um papel importante no sistema hemostático, principalmente, ao aderir ao vaso sanguíneo lesado, agregando com outras plaquetas, promovendo a formação do tampão plaquetário, facilitando e localizando a geração de trombina, que reforçará o tampão plaquetário, através da conversão de fibrinogênio em filamentos de fibrina (Parise et al, 2001;Kroll;Afshar-Kharghan, 2012;Chang, 2012 Rizvi, 2001;Levine et al, 2004;Swerdlow, et al, 2008).…”