Pulmonary vascular remodeling patterns and expression of general control nonderepressible 2 (GCN2) in pulmonary veno-occlusive disease

Nossent, Esther J.; Antigny, Fabrice; Montani, David; Bogaard, Harm Jan; Ghigna, Maria Rosa; Lambert, Mélanie; Montpréville, Vincent de; Girerd, Barbara; Jaïs, Xavier; Savale, Laurent; Mercier, Olaf; Fadel, Élie; Soubrier, Florent; Sitbon, Olivier; Simonneau, Gérald; Vonk‐Noordegraaf, Anton; Humbert, Marc; Perros, Frédèric; Dorfmüller, Peter

doi:10.1016/j.healun.2017.09.022

Cited by 53 publications

(53 citation statements)

References 29 publications

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“…Several cancer treatment-related mechanisms may precipitate the onset of PVOD, with the common mechanism likely to relate to venous endothelial injury from cytotoxic chemotherapy or irradiation [79,80]. PVOD is a rare, devastating form of PAH, classified as group 1' PH, characterised by widespread fibrous intimal proliferation of septal veins and preseptal venules also often with pulmonary capillary dilatation and proliferation [81] and substantial remodelling of the small pulmonary arteries [82]. Clinical features include marked oxygen desaturation and very low gas transfer, with a radiographic triad of interlobular septal thickening, pleural effusions and lymphadenopathy.…”

Section: Pvod Induced By Cancer Therapiesmentioning

confidence: 99%

Tumoral pulmonary hypertension

et al. 2019

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Tumoral pulmonary hypertension (PH) comprises a variety of subtypes in patients with a current or previous malignancy. Tumoral PH principally includes the tumour-related pulmonary microvascular conditions pulmonary tumour microembolism and pulmonary tumour thrombotic microangiopathy. These inter-related conditions are frequently found inpost mortemspecimens but are notoriously difficult to diagnoseante mortem. The outlook for patients remains extremely poor although there is some emerging evidence that pulmonary vasodilators and anti-inflammatory approaches may improve survival. Tumoral PH also includes pulmonary macroembolism and tumours that involve the proximal pulmonary vasculature, such as angiosarcoma; both may mimic pulmonary embolism and chronic thromboembolic PH. Finally, tumoral PH may develop in response to treatments of an underlying malignancy. There is increasing interest in pulmonary arterial hypertension induced by tyrosine kinase inhibitors, such as dasatanib. In addition, radiotherapy and chemotherapeutic agents such as mitomycin-C can cause pulmonary veno-occlusive disease. Tumoral PH should be considered in any patient presenting with unexplained PH, especially if it is poorly responsive to standard approaches or there is a history of malignancy. This article will describe subtypes of tumoral PH, their pathophysiology, investigation and management options in turn.

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Section: Pvod Induced By Cancer Therapiesmentioning

confidence: 99%

Tumoral pulmonary hypertension

et al. 2019

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“…Moreover, reduced GCN2 expression in the lung vasculature has been shown in experimental models and human PVOD. 61 Interesting, GCN2 dysfunction may be also involved in PAH pathogenesis, 70 highlighting its key role in pulmonary vascular remodeling.…”

Section: Pathogenesismentioning

confidence: 99%

“…72 However, recent quantitative morphometric data from our institution have shown that substantial constrictive remodeling of pulmonary muscular-type arteries (between 70 and 300 mm in diameter) is virtually always present in PVOD. 70 In this new light, the clear-cut discrimination between a primary pulmonary venous and a primary pulmonary arterial disease (PVOD versus PAH) appears questionable. Nonetheless, morphologic differences still persist, and the so-called plexiform lesions found in PAH are virtually never observed in patients with clinical and histologically confirmed PVOD (Figure 2).…”

Section: Histopathological Findingsmentioning

confidence: 99%

Understanding the Similarities and Differences between Hepatic and Pulmonary Veno-Occlusive Disease

Günther

Perros

Rautou

et al. 2019

The American Journal of Pathology

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“…Recently, Nossent et al demonstrated that vein smooth muscle hyperplasia was more preponderant in EIF2AK4 mutation-carriers. 26 Another common finding in PVOD is also the dilation of lymphatic vessel along visceral pleura and within the interlobular septa.…”

Section: Pulmonary Veno-occlusive Disease (Pvod)mentioning

confidence: 99%

“…The degree of arterial remodeling in PVOD carrying EIF2AK4 mutation is quite more marked compared to non-carriers. 26 Plexiform lesions have never been described in lung explants from patients with PVOD (with clinically probable PVOD and significant pulmonary venous changes in histology on explants). In our experience, this also means that, since pulmonary arterial and venous changes can be present in PAH and PVOD, at least PCH-like foci, a hallmark of PVOD, are virtually never found in combination with plexiform lesions.…”

Section: Pulmonary Veno-occlusive Disease (Pvod)mentioning

confidence: 99%

Pulmonary vascular disease and pulmonary hypertension

Ghigna¹,

Dorfmüller²

2019

Diagnostic Histopathology

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Pulmonary hypertension (PH) is a devastating condition that ultimately leads to right heart failure and death, if untreated. The morphological correlate for clinically relevant PH is pulmonary vascular disease that may concern all vascular compartments of the lung: pulmonary arteries, capillaries and veins, but also systemic lung vessels, commonly known as bronchial arteries and vasa vasorum. The recent diagnostic PH classification at the PH World Symposium in Nice, France, redefined five PH groups based on pathophysiological, histological and clinical differences. This article reviews the rationale of histology/pathology and, partly, pathobiology that has led to these different categories of PH. Even if aetiology and initial pathophysiology discriminate these groups to some extent, it has become clear that several diseaserelevant pathomechanisms are shared between the groups, leading to comparable therapeutic molecular targets, such as phosphodiesterase-5 inhibitors for PAH (group 1 in the Nice classification) and soluble guanylate cyclase agonists in CTEPH (group 4 of the Nice classification). When considering PH group 2 (PH due to left heart disease), its histological appearance, with remodelled small pulmonary veins and arteries, and its haemodynamics in some patients suggest an overreacting pre-capillary vasculature in response to left heart failure. Thus the still-used descriptor 'orphan disease' might one day no longer be used in relation to PH. Indeed, PH is a condition that represents a global health issue, and hence is worth a closer look and a thorough definition from the perspective of the pathologist.

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Pulmonary vascular remodeling patterns and expression of general control nonderepressible 2 (GCN2) in pulmonary veno-occlusive disease

Cited by 53 publications

References 29 publications

Tumoral pulmonary hypertension

Tumoral pulmonary hypertension

Understanding the Similarities and Differences between Hepatic and Pulmonary Veno-Occlusive Disease

Pulmonary vascular disease and pulmonary hypertension

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