Finding a Needle in a Haystack

Michelhaugh, Sam A.; Januzzi, James L.

doi:10.1016/j.jacbts.2020.07.007

Cited by 23 publications

(8 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alterations of plasma proteins in heart failure have been studied extensively to identify disease-specific or prognostic signatures (reviewed by Michelhaugh et al [20], Adamo et al [21], and Liu et al [22]). However, there are few studies that refer to welldefined cohorts of patients with cardiomyopathies [23][24][25], and the results of these studies depend on the methods used.…”

Section: Discussionmentioning

confidence: 99%

Integrative Analyses of Circulating Proteins and Metabolites Reveal Sex Differences in the Associations with Cardiac Function among DCM Patients

Hannemann,

Ameling,

Lehnert

et al. 2024

IJMS

View full text Add to dashboard Cite

Dilated cardiomyopathy (DCM) is characterized by reduced left ventricular ejection fraction (LVEF) and left or biventricular dilatation. We evaluated sex-specific associations of circulating proteins and metabolites with structural and functional heart parameters in DCM. Plasma samples (297 men, 71 women) were analyzed for proteins using Olink assays (targeted analysis) or LC-MS/MS (untargeted analysis), and for metabolites using LC MS/MS (Biocrates AbsoluteIDQ p180 Kit). Associations of proteins (n = 571) or metabolites (n = 163) with LVEF, measured left ventricular end diastolic diameter (LVEDDmeasured), and the dilation percentage of LVEDD from the norm (LVEDDacc. to HENRY) were examined in combined and sex-specific regression models. To disclose protein–metabolite relations, correlation analyses were performed. Associations between proteins, metabolites and LVEF were restricted to men, while associations with LVEDD were absent in both sexes. Significant metabolites were validated in a second independent DCM cohort (93 men). Integrative analyses demonstrated close relations between altered proteins and metabolites involved in lipid metabolism, inflammation, and endothelial dysfunction with declining LVEF, with kynurenine as the most prominent finding. In DCM, the loss of cardiac function was reflected by circulating proteins and metabolites with sex-specific differences. Our integrative approach demonstrated that concurrently assessing specific proteins and metabolites might help us to gain insights into the alterations associated with DCM.

show abstract

Section: Discussionmentioning

confidence: 99%

Integrative Analyses of Circulating Proteins and Metabolites Reveal Sex Differences in the Associations with Cardiac Function among DCM Patients

Hannemann,

Ameling,

Lehnert

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Global measures of protein abundance and modifications (proteomics) provide a complementary view to that of transcriptomics, with advantages including proximity to cellular function and the utility of proteins as clinical biomarkers. A variety of proteomics technologies have been applied for heart failure proteomics, including mass spectrometry, protein microarray, aptamers and proximity extension arrays, each of which has its advantages (Michelhaugh & Januzzi, 2020). In a wide survey of the field, an American Heart Association consensus statement noted the broad potential of proteomics to establish cause‐and‐effect mechanisms and signalling networks of cardiovascular disease (Lindsey et al., 2015).…”

Section: Technical Innovations To Assess Biological Diversitymentioning

confidence: 99%

Diversity of cells and signals in the cardiovascular system

Grandi

Navedo

Saucerman

et al. 2023

The Journal of Physiology

View full text Add to dashboard Cite

support-information-section). Ele Grandi is a Professor in the Department of Pharmacology, the Chair of the Biophysics Graduate Group, and a Chancellor's Fellow at the University of California Davis. Her research utilizes mathematical modelling and simulation as an interpretative and predictive science to investigate the mechanisms of cardiac arrhythmias. Manuel F. Navedo is a Professor in the Department of Pharmacology and the Chair of the Molecular, Cellular and Integrative Physiology Graduate Group at UC Davis. He is an established physiologist and vascular biologist examining mechanisms regulating vascular smooth muscle function in health and disease. Jeffrey J. Saucerman is a Professor of Biomedical Engineering and Cardiovascular Medicine at the University of Virginia. His research develops experimental and computational methods to discover molecular networks that regulate cardiac remodelling.

show abstract

“…In the last decade, high-throughput proteomics technologies using affinity reagents have emerged that have the potential to respond to the stated need [ 5 ]. These affinity-based technologies rely on different methods to measure a large number of proteins: one method which currently targets approximately 7000 human proteins uses slow off-rate modified aptamers (SOMAmer) which are modified short, single-stranded oligonucleotides as protein-binding reagents which are quantifiable by nucleic acid microarrays [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Proteomics for heart failure risk stratification: a systematic review

Kuku,

Oyetoro,

Hashemian

et al. 2024

BMC Med

View full text Add to dashboard Cite

Background Heart failure (HF) is a complex clinical syndrome with persistently high mortality. High-throughput proteomic technologies offer new opportunities to improve HF risk stratification, but their contribution remains to be clearly defined. We aimed to systematically review prognostic studies using high-throughput proteomics to identify protein signatures associated with HF mortality. Methods We searched four databases and two clinical trial registries for articles published from 2012 to 2023. HF proteomics studies measuring high numbers of proteins using aptamer or antibody-based affinity platforms on human plasma or serum with outcomes of all-cause or cardiovascular death were included. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. A third reviewer resolved conflicts. We assessed the risk of bias using the Risk Of Bias In Non-randomized Studies—of Exposure tool. Results Out of 5131 unique articles identified, nine articles were included in the review. The nine studies were observational; three used the aptamer platform, and six used the antibody platform. We found considerable heterogeneity across studies in measurement panels, HF definitions, ejection fraction categorization, follow-up duration, and outcome definitions, and a lack of risk estimates for most protein associations. Hence, we proceeded with a systematic review rather than a meta-analysis. In two comparable aptamer studies in patients with HF with reduced ejection fraction, 21 proteins were identified in common for the association with all-cause death. Among these, one protein, WAP four-disulfide core domain protein 2 was also reported in an antibody study on HFrEF and for the association with CV death. We proposed standardized reporting criteria to facilitate the interpretation of future studies. Conclusions In this systematic review of nine studies evaluating the association of proteomics with mortality in HF, we identified a limited number of proteins common across several studies. Heterogeneity across studies compromised drawing broad inferences, underscoring the importance of standardized approaches to reporting.

show abstract

Finding a Needle in a Haystack

Cited by 23 publications

References 52 publications

Integrative Analyses of Circulating Proteins and Metabolites Reveal Sex Differences in the Associations with Cardiac Function among DCM Patients

Integrative Analyses of Circulating Proteins and Metabolites Reveal Sex Differences in the Associations with Cardiac Function among DCM Patients

Diversity of cells and signals in the cardiovascular system

Proteomics for heart failure risk stratification: a systematic review

Contact Info

Product

Resources

About