Systems Genomics Identifies a Key Role for Hypocretin/Orexin Receptor-2 in Human Heart Failure

Pérez, Marco; Pavlović, Aleksandra; Shang, Ching; Wheeler, Matthew T.; Miller, Clint L.; Liu, Jing; Dewey, Frederick E.; Pan, Stephen; Thanaporn, Porama; Absher, Devin; Brandimarto, Jeffrey; Salisbury, Heidi; Chan, Khin; Mukherjee, Rupak; Konadhode, Roda P.; Myers, R; Sedehi, Daniel; Scammell, Thomas E.; Quertermous, Thomas; Cappola, Thomas P.; Ashley, Euan A.

doi:10.1016/j.jacc.2015.09.061

Cited by 32 publications

(24 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1,6,7 Other factors reported to associate with LVRR, such as the presence of the minor allele of re777652, a hypocretin receptor-2. 17 Recently, hs-TnT has been reported to associate with outcomes in HF with a meta-analysis of studies suggesting a level < 18 ng/L to predict lower risk of death and hospitalization, but this level was not tested for prediction of reverse remodelling. 18 Others have suggested superior predictive strength for LV recovery of circulating ST2 level, where a score has been developed and validated.…”

Section: Predictors Of Late Left Ventricular Reverse Remodellingmentioning

confidence: 99%

Circulating troponin and further left ventricular ejection fraction improvement in patients with previously recovered left ventricular ejection fraction

et al. 2020

View full text Add to dashboard Cite

Aims The aim of this study is to determine factors associated with long-term recovery of left ventricular ejection fraction (LVEF) in patients with heart failure with reduced EF (HFrEF) and if further recovery also occurs in this group. Methods and results Among 621 participants enrolled in the Alberta Heart Failure Etiology and Analysis Team (HEART) Study, 316 with Stage C HF underwent comprehensive imaging and biomarker testing at enrolment and at 1-year follow up. Using pre-enrolment data, HF with recovered EF (HFrecEF) was defined as an absolute improvement ≥5% in LVEF from the prior lowest LVEF value, with a final LVEF value > 35% at or prior to study baseline. Participants with all LVEF > 40% were included for comparison. Hospitalization-free survival to 5 years was performed. The median cohort age was 66 years, and time from diagnosis was 4 years; 82% were male patients. Of the 316 patients, 95 (30%) patients had HFrecEF and 56 (18%) patients pHFrEF. On multivariate analysis, only shorter duration of HF was predictive of HFrecEF status. Over 1 year, LVEF increased in the HFrecEF group 4.0% (0.15-7.90, P = 0.042) as compared with persistent HFrEF, who in turn demonstrated higher baseline serum high sensitivity Troponin-T with further increase at follow up 0.55 (0.33-0.86, P = 0.011). No change in any parameter in the HFpEF/HFmrEF group at follow up was observed. Conclusions Patients with HFrecEF demonstrate evidence of additional late improvement in LVEF and unchanged troponin levels, in contrast to those with persistent HFrEF, where LVEF does not improve and serum troponin rises over time. These data help to inform mechanisms relating to late LV remodelling.

show abstract

Section: Predictors Of Late Left Ventricular Reverse Remodellingmentioning

confidence: 99%

Circulating troponin and further left ventricular ejection fraction improvement in patients with previously recovered left ventricular ejection fraction

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The search is still open for novel biomarkers useful for prognosis and guide therapy in HF patients 14 , 26 , 93 . Promising candidate biomarker may be: growth differential factor-15 (GDF-15), 94–96 carbohydrate antigen-125 (CA-125), 97–99 C-terminal pro-vasopressin (copectin), 100–103 mid-regional pro-adrenomedullin (MR-proADM), 100 , 101 , 104 NEP, 30 , 105 and orexin 93 , 106 . Some of these molecules have been utilized for many years as tumour-markers (CA-125), neuro-hormones (copeptin, MR-proADM) or inflammatory markers (GDF-15) in clinical practice.…”

Section: Novel Biomarkers and Multi-markers Modelsmentioning

confidence: 99%

“…Therefore, several studies are available on their biological activity and variation, pathophysiological and clinical relevance, reference range values and analytical characteristic of assay methods 93 . Conversely, there are scarce data on neprilysin 30 and orexin, 106–108 which should be considered as biomarkers in the early discovery phase and still under evaluation. A detailed discussion of that clinical relevance of these promising HF biomarkers is out of the aim of this executive summary and interested readers can consult the references for more information.…”

Section: Novel Biomarkers and Multi-markers Modelsmentioning

confidence: 99%

ANMCO/ELAS/SIBioC Consensus Document: biomarkers in heart failure

Aspromonte

Gulizia

Clerico

et al. 2017

European Heart Journal Supplements

View full text Add to dashboard Cite

Biomarkers have dramatically impacted the way heart failure (HF) patients are evaluated and managed. A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological or pathogenic processes, or pharmacological responses to a therapeutic intervention. Natriuretic peptides [B-type natriuretic peptide (BNP) and N-terminal proBNP] are the gold standard biomarkers in determining the diagnosis and prognosis of HF, and a natriuretic peptide-guided HF management looks promising. In the last few years, an array of additional biomarkers has emerged, each reflecting different pathophysiological processes in the development and progression of HF: myocardial insult, inflammation, fibrosis, and remodelling, but their role in the clinical care of the patient is still partially defined and more studies are needed before to be well validated. Moreover, several new biomarkers have the potential to identify patients with early renal dysfunction and appear to have promise to help the management cardio-renal syndrome. With different biomarkers reflecting HF presence, the various pathways involved in its progression, as well as identifying unique treatment options for HF management, a closer cardiologist-laboratory link, with a multi-biomarker approach to the HF patient, is not far ahead, allowing the unique opportunity for specifically tailoring care to the individual pathological phenotype.

show abstract

“…Orexins bind their cognate G-protein–coupled receptors (GPCRs), orexin receptor type 1 (OX1R, also named as Hcrtr-1) and type 2 (OX2R, or Hcrtr-2), which activate different downstream signal pathways, thereby exerting a variety of physiological functions (Sakurai et al, 1998 ). Orexin and orexin receptors are ectopically expressed in many diseases (Perez et al, 2015 ; Imperatore et al, 2017 ), especially neurological disorders (Feng et al, 2014 ; Liguori et al, 2014 ), suggesting that the orexin/receptor pathway plays critical roles in the pathology and pathogenesis of these illnesses. In this review article, we focus on the expression levels and physiological functions of orexins and their receptors.…”

Section: Introductionmentioning

confidence: 99%

The Orexin/Receptor System: Molecular Mechanism and Therapeutic Potential for Neurological Diseases

Wang

et al. 2018

Front. Mol. Neurosci.

143

View full text Add to dashboard Cite

Orexins, also known as hypocretins, are two neuropeptides secreted from orexin-containing neurons, mainly in the lateral hypothalamus (LH). Orexins orchestrate their effects by binding and activating two G-protein–coupled receptors (GPCRs), orexin receptor type 1 (OX1R) and type 2 (OX2R). Orexin/receptor pathways play vital regulatory roles in many physiological processes, especially feeding behavior, sleep–wake rhythm, reward and addiction and energy balance. Furthermore several reports showed that orexin/receptor pathways are involved in pathological processes of neurological diseases such as narcolepsy, depression, ischemic stroke, drug addiction and Alzheimer’s disease (AD). This review article summarizes the expression patterns, physiological functions and potential molecular mechanisms of the orexin/receptor system in neurological diseases, providing an overall framework for considering these pathways from the standpoints of basic research and clinical treatment of neurological diseases.

show abstract

Systems Genomics Identifies a Key Role for Hypocretin/Orexin Receptor-2 in Human Heart Failure

Abstract: A systems approach identified a novel genetic contribution to human HF and a promising therapeutic agent efficacious in an HF model.

Cited by 32 publications

References 39 publications

Circulating troponin and further left ventricular ejection fraction improvement in patients with previously recovered left ventricular ejection fraction

Circulating troponin and further left ventricular ejection fraction improvement in patients with previously recovered left ventricular ejection fraction

ANMCO/ELAS/SIBioC Consensus Document: biomarkers in heart failure

The Orexin/Receptor System: Molecular Mechanism and Therapeutic Potential for Neurological Diseases

Contact Info

Product

Resources

About