Iron Homeostasis and Pulmonary Hypertension

Cotroneo, Emanuele; Ashek, Ali; Wang, Lei; Wharton, John; Dubois, Olivier; Bozorgi, Sophie S; Busbridge, Mark; Alavian, Kambiz N.; Wilkins, Martin R.; Zhao, Lan

doi:10.1161/circresaha.116.305265

Cited by 102 publications

(50 citation statements)

References 49 publications

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“…SNP variation in those 65 genes was significantly related to disorders of iron metabolism (n = 111 cases, P = 4.8 × 10 −9 ). This finding reinforces several recent findings related to abnormal iron metabolism in PAH [41][42][43][44] and suggests a possible genetic correlation, while also identifying specific genes of potential experimental and therapeutic interest.…”

Section: Development Of Ph Cohortssupporting

confidence: 90%

Integration of Complex Data Sources to Provide Biologic Insight into Pulmonary Vascular Disease (2015 Grover Conference Series)

Brittain

Chan

2016

Pulm. circ.

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The application of complex data sources to pulmonary vascular diseases is an emerging and promising area of investigation. The use of -omics platforms, in silico modeling of gene networks, and linkage of large human cohorts with DNA biobanks are beginning to bear biologic insight into pulmonary hypertension. These approaches to high-throughput molecular phenotyping offer the possibility of discovering new therapeutic targets and identifying variability in response to therapy that can be leveraged to improve clinical care. Optimizing the methods for analyzing complex data sources and accruing large, well-phenotyped human cohorts linked to biologic data remain significant challenges. Here, we discuss two specific types of complex data sources-gene regulatory networks and DNA-linked electronic medical record cohorts-that illustrate the promise, challenges, and current limitations of these approaches to understanding and managing pulmonary vascular disease.

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Section: Development Of Ph Cohortssupporting

confidence: 90%

Integration of Complex Data Sources to Provide Biologic Insight into Pulmonary Vascular Disease (2015 Grover Conference Series)

Brittain

Chan

2016

Pulm. circ.

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“…Further experiments indicated that this may result from metabolic changes induced by iron deficiency, including a shift towards aerobic glycolysis [81]. In this animal model, pulmonary vascular remodelling was reversed by iron supplementation, supporting its use as a potential treatment option in PH patients [81].…”

Section: Iron Homeostasismentioning

confidence: 73%

Section: Iron Homeostasismentioning

confidence: 99%

“…A study by COTRONEO et al [81] has demonstrated for the first time that pulmonary vascular remodelling can occur as a result of chronic iron deficiency in rats. Further experiments indicated that this may result from metabolic changes induced by iron deficiency, including a shift towards aerobic glycolysis [81]. In this animal model, pulmonary vascular remodelling was reversed by iron supplementation, supporting its use as a potential treatment option in PH patients [81].…”

Section: Iron Homeostasismentioning

confidence: 99%

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Pathobiology of pulmonary arterial hypertension: understanding the roads less travelled

Hemnes

Humbert

2017

Eur Respir Rev

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The pathobiology of pulmonary arterial hypertension (PAH) is complex and incompletely understood. Although three pathogenic pathways have been relatively well characterised, it is widely accepted that dysfunction in a multitude of other cellular processes is likely to play a critical role in driving the development of PAH. Currently available therapies, which all target one of the three well-characterised pathways, provide significant benefits for patients; however, PAH remains a progressive and ultimately fatal disease. The development of drugs to target alternative pathogenic pathways is, therefore, an attractive proposition and one that may complement existing treatment regimens to improve outcomes for patients. Considerable research has been undertaken to identify the role of the less well-understood pathways and in this review we will highlight some of the key discoveries and the potential for utility as therapeutic targets.

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“…Further, vascular recruitment and distention of pulmonary resistance vessels is known to occur in response to cardiac output increases, which causes PVR to decrease. Finally, hemodilution decreases viscosity and may thus lower PVR, whereas iron deprivation will enhance hypoxic pulmonary vasoconstriction [14].…”

Section: Pulmonary Vascular Resistancementioning

confidence: 99%

Fluid therapy in critically ill patients: perspectives from the right heart

Elbers

Rodrigus²,

Nossent

et al. 2015

Anaesthesiol Intensive Ther

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As right heart function can affect outcome in the critically ill patient, a thorough understanding of factors determining right heart performance in health and disease is pivotal for the critical care physician. This review focuses on fluid therapy, which remains controversial in the setting of impending or overt right heart failure. In this context, we will attempt to elucidate which patients are likely to benefit from fluid administration and for which patients fluid therapy would likely be harmful. Following a general discussion of right heart function and failure, we specifically focus on important causes of right heart failure in the critically ill, i.e. sepsis induced myocardial dysfunction, the acute respiratory distress syndrome, acute pulmonary embolism and the effects of positive pressure ventilation. It is argued that fluid therapy should always be cautiously administered with the right heart in mind, which calls for close multimodal monitoring.

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Iron Homeostasis and Pulmonary Hypertension

Abstract: These data suggest a major role for iron in pulmonary vascular homeostasis and support the clinical evaluation of iron replacement in patients with pulmonary hypertension.

Cited by 102 publications

References 49 publications

Integration of Complex Data Sources to Provide Biologic Insight into Pulmonary Vascular Disease (2015 Grover Conference Series)

Integration of Complex Data Sources to Provide Biologic Insight into Pulmonary Vascular Disease (2015 Grover Conference Series)

Pathobiology of pulmonary arterial hypertension: understanding the roads less travelled

Fluid therapy in critically ill patients: perspectives from the right heart

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