Systems analysis of oxidant stress in the vasculature

Handy, Diane E.; Loscalzo, Joseph; Leopold, Jane A.

doi:10.1002/iub.1221

Cited by 5 publications

(4 citation statements)

References 46 publications

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“…A second study in the project enriched the initial network medicine analysis [ 34 - 36 ]) from the Biobridge dataset [ 33 ] by including additional "omics" information [ 27 , 28 ], as well as an extended set of measurements on nitroso-redox balance carried out in blood and in skeletal muscle [ 28 ]. The purpose of the network approach described in detail in [ 31 ] was to compare healthy subjects and COPD patients in terms of the relationships among relevant metabolic pathways governing cellular bioenergetics, protein balance, and skeletal muscle remodeling paying particular attention to the role of nitroso-redox disequilibrium in the network modeling.…”

Section: Methodsmentioning

confidence: 99%

“…Finally, a third study undertaken within Synergy-COPD addressed the analysis of abnormal training adaptations comparing healthy subjects and COPD from the Biobridge database. Two different modeling strategies were undertaken: targeted probabilistic network modeling [ 34 , 37 , 38 ] and a Thomas network approach, as described in detail in [ 31 ]. In the former, associations between estimated skeletal muscle ROS levels obtained with the integrated deterministic model were compared with actual measurements pre- and post-training carried out both in blood and skeletal muscle.…”

Section: Methodsmentioning

confidence: 99%

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Chronic Obstructive Pulmonary Disease heterogeneity: challenges for health risk assessment, stratification and management

et al. 2014

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Background and hypothesisHeterogeneity in clinical manifestations and disease progression in Chronic Obstructive Pulmonary Disease (COPD) lead to consequences for patient health risk assessment, stratification and management. Implicit with the classical "spill over" hypothesis is that COPD heterogeneity is driven by the pulmonary events of the disease. Alternatively, we hypothesized that COPD heterogeneities result from the interplay of mechanisms governing three conceptually different phenomena: 1) pulmonary disease, 2) systemic effects of COPD and 3) co-morbidity clustering, each of them with their own dynamics.Objective and methodTo explore the potential of a systems analysis of COPD heterogeneity focused on skeletal muscle dysfunction and on co-morbidity clustering aiming at generating predictive modeling with impact on patient management. To this end, strategies combining deterministic modeling and network medicine analyses of the Biobridge dataset were used to investigate the mechanisms of skeletal muscle dysfunction. An independent data driven analysis of co-morbidity clustering examining associated genes and pathways was performed using a large dataset (ICD9-CM data from Medicare, 13 million people). Finally, a targeted network analysis using the outcomes of the two approaches (skeletal muscle dysfunction and co-morbidity clustering) explored shared pathways between these phenomena.Results(1) Evidence of abnormal regulation of skeletal muscle bioenergetics and skeletal muscle remodeling showing a significant association with nitroso-redox disequilibrium was observed in COPD; (2) COPD patients presented higher risk for co-morbidity clustering than non-COPD patients increasing with ageing; and, (3) the on-going targeted network analyses suggests shared pathways between skeletal muscle dysfunction and co-morbidity clustering.ConclusionsThe results indicate the high potential of a systems approach to address COPD heterogeneity. Significant knowledge gaps were identified that are relevant to shape strategies aiming at fostering 4P Medicine for patients with COPD.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Chronic Obstructive Pulmonary Disease heterogeneity: challenges for health risk assessment, stratification and management

et al. 2014

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“…There is substantial genetic overlap between selected, common human disease pathophenotypes, 54 which has been demonstrated using genome‐wide association studies (GWASs) 55 and systems biology network methods 56 . The GWASs, which are performed using vast numbers of patients sharing a common disease, have identified genetic variability (i.e., single‐nucleotide polymorphisms) in association with disease prevalence.…”

Section: The Systems Pathobiology Of Pah: a Network Medicine Approachmentioning

confidence: 99%

Emerging Hemodynamic Signatures of the Right Heart (Third International Right Heart Failure Summit, Part 2)

Maron

2014

Pulm. circ.

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Despite the importance of preserved right ventricular structure and function with respect to outcome across the spectrum of lung, cardiac, and pulmonary vascular diseases, only recently have organized efforts developed to consider the pulmonary vascular-right ventricular apparatus as a specific unit within the larger context of cardiopulmonary pathophysiology. The Third International Right Heart Failure Summit (Boston, MA) was a multidisciplinary event dedicated to promoting a dialogue about the scientific and clinical basis of right heart disease. The current review provides a synopsis of key discussions presented during the section of the summit titled "Emerging Hemodynamic Signatures of the Right Heart." Specifically, topics emphasized in this element of the symposium included (1) the effects of pulmonary vascular dysfunction at rest or provoked by exercise on the right ventricular pressure-volume relationship, (2) the role of pressure-volume loop analysis as a method to characterize right ventricular inefficiency and predict right heart failure, and (3) the importance of a systems biology approach to identifying novel factors that contribute to pathophenotypes associated with pulmonary arterial hypertension and/or right ventricular dysfunction. Collectively, these concepts frame a forward-thinking paradigm shift in the approach to right heart disease by emphasizing factors that regulate the transition from adaptive to maladaptive right ventricular-pulmonary vascular (patho)physiology.

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“…Moreover, the results from these studies should be subjected to novel analytical methods, such as systems biology and network analysis, for the discovery of previously unknown genetic factors and related signaling pathways that contribute to disease pathogenesis. These analyses may also identify targets unique to microvascular dysfunction that can be exploited for pharmacotherapeutic intervention [11]. …”

mentioning

confidence: 99%