Abstract:Severe forms of pulmonary arterial hypertension (PAH) are most frequently the consequence of a lumen-obliterating angiopathy. One pathobiological model is that the initial pulmonary vascular endothelial cell injury and apoptosis is followed by the evolution of phenotypically altered, apoptosis-resistant, proliferating cells and an inflammatory vascular immune response. Although there may be a vasoconstrictive disease component, the increased pulmonary vascular shear stress in established PAH is caused largely … Show more
“…A number of X encoded proteins regulate apoptosis which is of interest in the context of PAH where resistance to apoptosis is a prominent feature in the remodelled vasculature [ 130 , 131 ]. Apoptosis-inducing factor mitochondria associated-1 (AIFM1) is a mitochondrial flavoprotein that primarily regulates mitochondrial energy metabolism under normal cellular conditions and is involved in regulation of apoptosis.…”
Section: The X Chromosome In Pulmonary Hypertensionmentioning
Pulmonary hypertension (PH) is a condition characterised by an abnormal elevation of pulmonary artery pressure caused by an increased pulmonary vascular resistance, frequently leading to right ventricular failure and reduced survival. Marked sexual dimorphism is observed in patients with pulmonary arterial hypertension, a form of pulmonary hypertension with a particularly severe clinical course. The incidence in females is 2–4 times greater than in males, although the disease is less severe in females. We review the contribution of the sex chromosomes to this sex dimorphism highlighting the impact of proteins, microRNAs and long non-coding RNAs encoded on the X and Y chromosomes. These genes are centrally involved in the cellular pathways that cause increased pulmonary vascular resistance including the production of reactive oxygen species, altered metabolism, apoptosis, inflammation, vasoconstriction and vascular remodelling. The interaction with genetic mutations on autosomal genes that cause heritable pulmonary arterial hypertension such as bone morphogenetic protein 2 (BMPR2) are examined. The mechanisms that can lead to differences in the expression of genes located on the X chromosomes between females and males are also reviewed. A better understanding of the mechanisms of sex dimorphism in this disease will contribute to the development of more effective therapies for both women and men.
“…A number of X encoded proteins regulate apoptosis which is of interest in the context of PAH where resistance to apoptosis is a prominent feature in the remodelled vasculature [ 130 , 131 ]. Apoptosis-inducing factor mitochondria associated-1 (AIFM1) is a mitochondrial flavoprotein that primarily regulates mitochondrial energy metabolism under normal cellular conditions and is involved in regulation of apoptosis.…”
Section: The X Chromosome In Pulmonary Hypertensionmentioning
Pulmonary hypertension (PH) is a condition characterised by an abnormal elevation of pulmonary artery pressure caused by an increased pulmonary vascular resistance, frequently leading to right ventricular failure and reduced survival. Marked sexual dimorphism is observed in patients with pulmonary arterial hypertension, a form of pulmonary hypertension with a particularly severe clinical course. The incidence in females is 2–4 times greater than in males, although the disease is less severe in females. We review the contribution of the sex chromosomes to this sex dimorphism highlighting the impact of proteins, microRNAs and long non-coding RNAs encoded on the X and Y chromosomes. These genes are centrally involved in the cellular pathways that cause increased pulmonary vascular resistance including the production of reactive oxygen species, altered metabolism, apoptosis, inflammation, vasoconstriction and vascular remodelling. The interaction with genetic mutations on autosomal genes that cause heritable pulmonary arterial hypertension such as bone morphogenetic protein 2 (BMPR2) are examined. The mechanisms that can lead to differences in the expression of genes located on the X chromosomes between females and males are also reviewed. A better understanding of the mechanisms of sex dimorphism in this disease will contribute to the development of more effective therapies for both women and men.
“…Regardless of classification, these conditions are associated with extremely poor outcomes. Multiple mechanisms have been proposed suggesting the link between cancer and PH: 1) pulmonary vascular endothelial cell injury and apoptosis leading to vasoconstrictive disease ( 3 ); 2) thromboembolic disease; 3) tumor emboli; 4) chemotherapy-related causes; 5) vascular remodeling due to inflammatory cell accumulation ( 4 ); 6) intravascular tumor (i.e., sarcoma); and 7) external malignant compression of the pulmonary artery.…”
Tumoral obstruction is a small, but broadly defined, category of pulmonary hypertension that encompasses microvascular tumor emboli, tumor thrombotic microangiopathy, and macrovascular tumor obstruction within the pulmonary circulation. We present 4 patients with solid tumors, severe pre-capillary pulmonary hypertension, right ventricular failure, and pulmonary veno-occlusive–like disease. (
Level of Difficulty: Advanced.
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“…Das IPS tritt bei ungefähr 2-8 % aller Patienten innerhalb von 12 Tagen nach allogener HSCT auf und führt bei über 60 % der Betroffenen zum Tode [20]. Die klinische Präsentation ist äußerst vielfältig und wird zeitlich unterschiedlich beobachtet: Es wurden auch Gemeinsamkeiten unterschiedlicher Erkrankungen festgestellt: Beispielsweise gibt es pathophysiologische Charakteristika bei der pulmonal arteriellen Hypertonie (PAH) wie Induktion von Proliferation, Antiapoptose und Angiogenese, metabolische Dysregulation und proinflammatorische Stimuli, die auch bei malignen Tumoren beobachtet werden [22]. Auch wenn pulmonale Epithelzellen bei der PAH nicht maligne entarten, ist es doch nachvollziehbar, dass Antitumortherapien auch direkt vorbestehende Erkrankungen wie die PAH beeinflussen können.…”
Section: Knochenmarktransplantation Bei Malignen Hämatologischen Kranunclassified
“…Es wurden auch Gemeinsamkeiten unterschiedlicher Erkrankungen festgestellt: Beispielsweise gibt es pathophysiologische Charakteristika bei der pulmonal arteriellen Hypertonie ( PAH PAH ) wie Induktion von Proliferation, Antiapoptose und Angiogenese, metabolische Dysregulation und proinflammatorische Stimuli, die auch bei malignen Tumoren Maligner Tumor beobachtet werden [ 22 ]. Auch wenn pulmonale Epithelzellen bei der PAH nicht maligne entarten, ist es doch nachvollziehbar, dass Antitumortherapien auch direkt vorbestehende Erkrankungen wie die PAH beeinflussen können.…”
Section: Einflüsse Auf Vorbestehende Pulmonale Erkrankungenunclassified
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