Advertisement

Topics

The human platelet transcriptome and proteome is altered and pro-thrombotic functional responses are increased during prolonged hypoxia exposure at high altitude.

07:00 EST 5th February 2019 | BioPortfolio

Summary of "The human platelet transcriptome and proteome is altered and pro-thrombotic functional responses are increased during prolonged hypoxia exposure at high altitude."

Exposure to hypoxia, through ascension to high altitudes (HAs), air travel, or human disease, is associated with an increased incidence of thrombosis in some settings. Mechanisms underpinning this increased thrombosis risk remain incompletely understood, and the effects of more sustained hypoxia on the human platelet molecular signature and associated functional responses have never been examined. We examined the effects of prolonged (≥2 months continuously) hypobaric hypoxia on platelets isolated from subjects residing at HA (3,700 meters) and, for comparison, matched subjects residing under normoxia conditions at sea level (50 meters). Using complementary transcriptomic, proteomic, and functional methods, we identified that the human platelet transcriptome is markedly altered under prolonged exposure to hypobaric hypoxia at HA. Among the significantly, differentially expressed genes (mRNA and protein), were those having canonical roles in platelet activation and thrombosis, including membrane glycoproteins (e.g. GP4, GP6, GP9), integrin subunits (e.g. ITGA2B), and alpha-granule chemokines (e.g. SELP, PF4V1). Platelets from subjects residing at HA were hyperactive, as demonstrated by increased engagement and adhesion to fibrinogen, fewer alpha granules by transmission electron microscopy, increased circulating PF4 and ADP, and significantly enhanced clot retraction. In conclusion, we identify that prolonged hypobaric hypoxia exposure due to HA alters the platelet transcriptome and proteome, triggering increased functional activation responses that may contribute to thrombosis. Our findings may also have relevance across a range of human diseases where chronic hypoxia, platelet activation, and thrombosis are increased.

Affiliation

Journal Details

This article was published in the following journal.

Name: Platelets
ISSN: 1369-1635
Pages: 1-10

Links

DeepDyve research library

PubMed Articles [24648 Associated PubMed Articles listed on BioPortfolio]

New Insights into Platelet Signalling Pathways by Functional and Proteomic Approaches.

As circulating sentinels of vascular integrity, platelets act as crucial haemostatic cells as well as important inflammatory and immune cells, whereas under pathological conditions platelets drive thr...

A dichotomy in platelet activation: Evidence of different functional platelet responses to inflammatory versus haemostatic stimuli.

Platelets participate in inflammatory disorders through a variety of different functional responses, including chemotaxis, platelet-leukocyte complex formation and facilitation of leukocyte recruitmen...

Predictive value of platelet reactivity unit (PRU) value for thrombotic and hemorrhagic events during flow diversion procedures: a meta-analysis.

Platelet function testing prior to flow diversion procedures, although initially heavily debated, has seen a substantial increase in its adoption to assess the risk of operative and perioperative thro...

Functional Validation of microRNA-126-3p as a Platelet Reactivity Regulator Using Human Haematopoietic Stem Cells.

 Platelets are an abundant source of micro-ribonucleic acids (miRNAs) that may play a role in the regulation of platelet function. Some miRNAs, such as miR-126-3p, have been noted as potential bioma...

Role of Platelet Size Revisited-Function and Protein Composition of Large and Small Platelets.

Epidemiological studies found an association between increased platelet size and the risk for thrombotic complications, but functional differences of large and small platelets remain poorly understood...

Clinical Trials [9314 Associated Clinical Trials listed on BioPortfolio]

The Role of Platelet Surface α2β1 Integrin Expression as a Risk Factor in Thrombotic and/or Bleeding Complications

This study will begin to define these critical determinants for patients undergoing procedures in the hybrid interventional cardiology/cardiac surgery suite. In future studies, the data o...

Mitochondrial-related Platelet Transcript Expression Levels in Pre-diabetic Subjects Randomized to Metformin or Placebo

Diabetes mellitus (DM) imposes an approximate 2-fold increased risk of atherothrombosis. Patients with type 2 DM have a 2- to 4-fold increase in the risk of coronary artery disease (CAD) a...

Alterations in the Plasma Proteome of Early-Onset Severe Preeclampsia

The hypothesis of this study is that many plasma proteins are altered in concentration and structure in preeclampsia and the elucidation of these alterations will add to the poorly underst...

Post-Injury Platelet Biology: Mechanisms and Outcomes

Trauma-induced coagulopathy is a central cause of preventable deaths from hemorrhage after injury. The contribution and impact of altered post injury platelet biology on trauma-induced coa...

Dark Chocolate and Platelet Function in Humans

Cardiovascular disease is a major cause of mortality worldwide and responsible for one out of three global deaths. A main characteristic of cardiovascular disease is impaired blood flow an...

Medical and Biotech [MESH] Definitions

The diagnosis and treatment of human responses of individuals and groups to actual or potential health problems with the characteristics of altered functional ability and altered life-style. (American Nurses Association & Association of Rehabilitation Nurses. Standards of Rehabilitation Nursing Practice, 1986, p.2)

An acquired, congenital, or familial disorder caused by PLATELET AGGREGATION with THROMBOSIS in terminal arterioles and capillaries. Clinical features include THROMBOCYTOPENIA; HEMOLYTIC ANEMIA; AZOTEMIA; FEVER; and thrombotic microangiopathy. The classical form also includes neurological symptoms and end-organ damage, such as RENAL FAILURE.

Human alloantigens expressed only on platelets, specifically on platelet membrane glycoproteins. These platelet-specific antigens are immunogenic and can result in pathological reactions to transfusion therapy.

A rare, inherited platelet disorder characterized by a selective deficiency in the number and contents of platelet alpha-granules. It is associated with THROMBOCYTOPENIA, enlarged platelets, and prolonged bleeding time.

Diseases that result in THROMBOSIS in MICROVASCULATURE. The two most prominent diseases are PURPURA, THROMBOTIC THROMBOCYTOPENIC; and HEMOLYTIC-UREMIC SYNDROME. Multiple etiological factors include VASCULAR ENDOTHELIAL CELL damage due to SHIGA TOXIN; FACTOR H deficiency; and aberrant VON WILLEBRAND FACTOR formation.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Cardiology
Cardiology is a specialty of internal medicine.  Cardiac electrophysiology : Study of the electrical properties and conduction diseases of the heart. Echocardiography : The use of ultrasound to study the mechanical function/physics of the h...

Blood
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells.  In vertebrates, it is composed of blo...


Searches Linking to this Article