Epidemiology, Pathophysiology, Stratification, and Natural History of Pulmonary Embolism

Giordano, N.; Jansson, Paul S.; Young, Michael N.; Hagan, Kaitlin; Kabrhel, Christopher

doi:10.1053/j.tvir.2017.07.002

Cited by 110 publications

(117 citation statements)

References 54 publications

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“…First, we determined whether the JAK2V617F-positive Tie2FF1 mice developed spontaneous pulmonary thromboembolism, which is a common cause of sudden death. 28 We found increased thrombosis in the right ventricle and both main and segment pulmonary arteries in Tie2FF1 mice, but not in agematched Tie2-cre control mice. ( Figure 2C-D and 2F) In addition, although we did not observe thrombosis in the main (epicardial) coronary arteries, we found thrombosis in scattered coronary arterioles (microvessels) in some of the Tie2FF1 mice examined.…”

Section: Jak2v617f-positive Tie2ff1 Mice Have a Prothrombotic And Vasmentioning

confidence: 66%

Endothelial JAK2V617F mutation leads to thrombosis, vasculopathy, and cardiomyopathy in a murine model of myeloproliferative neoplasm

Castiglione

Mazzeo

Jiang

et al. 2019

Preprint

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Rational: The myeloproliferative neoplasms (MPNs) are clonal hematological malignancies characterized by hematopoietic stem cell expansion and overproduction of mature blood cells. Cardiovascular complications are the leading cause of morbidity and mortality in patients with MPNs. The acquired kinase mutation JAK2V617F plays a central role in these disorders. Mechanisms responsible for cardiovascular dysfunction in MPNs are not fully understood, limiting the effectiveness of current treatment. Objective: Vascular endothelial cells (ECs) play critical roles in the regulation of hemostasis and thrombosis. ECs carrying the JAK2V617F mutation can be detected in patients with MPNs. The goal of this study was to test the hypothesis that the JAK2V617F mutation alters endothelial function to promote cardiovascular complications in patients with MPNs. Methods and Results: We employed murine models of MPN in which the JAK2V617F mutation is expressed in specific cell lineages. When JAK2V617F is expressed in both blood cells and vascular ECs, the mice developed MPN and spontaneous, age-related dilated cardiomyopathy with an increased risk of sudden death as well as a prothrombotic and vasculopathy phenotype on histology evaluation. We showed that JAK2V617F-mutant ECs are required for this cardiovascular disease phenotype and the mutation can alter endothelial cell function. Finally, in a more therapeutically oriented approach, we demonstrated that transplantation with wild-type donor marrow cells can improve cardiac function by reversing the left ventricle remodeling process in this JAK2V617F-positive MPN murine model. Conclusions: These findings suggest that the JAK2V617F mutation alters vascular endothelial function to promote cardiovascular complications in MPNs. Therefore, targeting the MPN vasculature represents a promising new therapeutic strategy for patients with MPNs.

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Section: Jak2v617f-positive Tie2ff1 Mice Have a Prothrombotic And Vasmentioning

confidence: 66%

Endothelial JAK2V617F mutation leads to thrombosis, vasculopathy, and cardiomyopathy in a murine model of myeloproliferative neoplasm

Castiglione

Mazzeo

Jiang

et al. 2019

Preprint

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“…Venous thromboembolism is a major health problem with acute pulmonary embolism (PE) being its most serious clinical presentation (Cohen et al, 2007). PE occurs when a portion of a clot from a deep vein thrombosis breaks off, travels through the right heart, and eventually lodges in the pulmonary vasculature (Giordano et al, 2017). To this day, epidemiology of PE is difficult to determine, and its incidence is estimated around 100 to 200 cases per 100,000 people (Huang et al, 2014;Martinez et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…To this day, epidemiology of PE is difficult to determine, and its incidence is estimated around 100 to 200 cases per 100,000 people (Huang et al, 2014;Martinez et al, 2014). Well known risk factors that increase likelihood of developing PE include surgery, trauma, prolonged immobility, cancer and estrogen use (Giordano et al, 2017). Prompt diagnosis may be difficult, since its clinical signs and symptoms (dyspnea, pleuritic chest pain, cough) are non-specific.…”

Section: Introductionmentioning

confidence: 99%

Acute Massive Pulmonary Embolism with Direct Visualization of a Free-floating Right Heart Thrombus Successfully Treated with Fibrinolysis: A Case Report

et al. 2020

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Kaitalidou E.; Karapiperis D.; Makrakis V.; Kipourou M.; Petroglou D. 42)Abstract: A male patient with a history of immobilization due to motor weakness, was transferred to our emergency department after syncope during physiotherapy, with recorded hypotension. Transthoracic echocardiography showed severe dilatation of the right ventricle (RV), with apex hypercontractility and almost akinetic RV free wall. The above findings, in addition to the unexpected visualization of a large, free-floating, right atrial thrombus, a rare finding associated with high mortality, readily confirmed the clinical suspicion of acute pulmonary embolism (PE) causing circulatory collapse. Intravenous fibrinolysis and vasopressor therapy were successfully administered, and hemodynamic instability was soon alleviated.

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“…Deep vein thrombosis (DVT) refers to the formation of blood clots in deep venous lumen, causing blood flow disorders, and its prevalence increases with age . DVT with its major complications, post‐thrombotic syndrome (PTS) and pulmonary embolism (PE) can be life‐threatening, which is a global health problem . PTS consists of pain, swelling and even ulceration of the leg that can occur immediately after DVT or can delay the onset .…”

Section: Introductionmentioning

confidence: 99%

“…1,2 DVT with its major complications, post-thrombotic syndrome (PTS) and pulmonary embolism (PE) can be lifethreatening, which is a global health problem. [3][4][5] PTS consists of pain, swelling and even ulceration of the leg that can occur immediately after DVT or can delay the onset. [6][7][8] Prophylaxis and treatments for DVT patients include anticoagulation by heparin, vitamin K antagonists, and thrombin and Factor Xa inhibitors.…”

Section: Introductionmentioning

confidence: 99%

MiR‐205 promotes endothelial progenitor cell angiogenesis and deep vein thrombosis recanalization and resolution by targeting PTEN to regulate Akt/autophagy pathway and MMP2 expression

Sun

Xiao

et al. 2019

J Cellular Molecular Medi

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MicroRNAs (MiRNAs, MiRs) represent a class of conserved small non‐coding RNAs that affect post‐transcriptional gene regulation and play a vital role in angiogenesis, proliferation, apoptosis, migration and invasion. They are essential for a wide range of physiological and pathological processes, especially for vascular diseases. However, data concerning miRNAs in endothelial progenitor cells (EPCs) and deep vein thrombosis (DVT) remain incomplete. We explored miRNAs that modulate angiogenesis in EPCs and thrombolysis, and analysed their underlying mechanisms using a DVT model, dual‐luciferase reporter assay, qRT‐PCR, Western blot, immunofluorescence staining, flow cytometry analysis, CCK‐8 assay, angiogenesis assay, wound healing and Transwell assay. We found that miR‐205 enhanced the homing ability of EPCs to DVT sites and promoted thrombosis resolution and recanalization, which significantly reduced venous thrombus. Additionally, we demonstrated that miR‐205 overexpression significantly enhanced angiogenesis in vivo and in vitro, migration, invasion, F‐actin filaments and proliferation in EPCs, and inhibited cell apoptosis. Conversely, down‐regulation of miR‐205 played the opposite role in EPCs. Importantly, this study demonstrated that miR‐205 directly targeted PTEN to modulate the Akt/autophagy pathway and MMP2 expression, subsequently playing a key role in EPC function and DVT recanalization and resolution. These results elucidated the pro‐angiogenesis effects of miR‐205 in EPCs and established it as a potential target for DVT treatment.

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Epidemiology, Pathophysiology, Stratification, and Natural History of Pulmonary Embolism

Cited by 110 publications

References 54 publications

Endothelial JAK2V617F mutation leads to thrombosis, vasculopathy, and cardiomyopathy in a murine model of myeloproliferative neoplasm

Endothelial JAK2V617F mutation leads to thrombosis, vasculopathy, and cardiomyopathy in a murine model of myeloproliferative neoplasm

Acute Massive Pulmonary Embolism with Direct Visualization of a Free-floating Right Heart Thrombus Successfully Treated with Fibrinolysis: A Case Report

MiR‐205 promotes endothelial progenitor cell angiogenesis and deep vein thrombosis recanalization and resolution by targeting PTEN to regulate Akt/autophagy pathway and MMP2 expression

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