glycoproteomics-extracellular-matrix-method-for-intact-glycopeptide

Glycoproteomics of the Extracellular Matrix: A Method for Intact Glycopeptide Analysis Using Mass Spectrometry

Fibrosis is a hallmark of many cardiovascular diseases and is associated with the exacerbated secretion and deposition of the extracellular matrix (ECM). ...

King's College London

Extracellular matrix remodelling has been implicated in a number of vascular conditions, including venous hypertension and varicose veins. However, to date, no systematic analysis of matrix remodelling in human veins has been performed.

Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veins.

A series of potent PDGFR inhibitors has been identified. The series was optimized for duration of action in the lung. A novel kinase occupancy assay was used to directly measure target occupancy after i.t. dosing. Compound 25 shows 24 h occupancy of the PDGFR kinase domain, after a single i.t. dose and has efficacy at 0.03 mg/kg, in the rat moncrotaline model of pulmonary arterial hypertension. Examination of PK/PD data from the optimization effort has revealed in vitro:in vivo correlations which link duration of action in vivo with low permeability and high basicity and demonstrate that nonspecific binding to lung tissue increases with lipophilicity.

Optimization of Platelet-Derived Growth Factor Receptor (PDGFR) Inhibitors for Duration of Action, as an Inhaled Therapy for Lung Remodeling in Pulmonary Arterial Hypertension.

Caveats of Untargeted Metabolomics for Biomarker Discovery.

While lipid abnormalities continue to account for over 60% of the population attributable risk for myocardial infarction, the well-known inverse correlation between plasma high-density lipoprotein (HDL) cholesterol and cardiovascular risk has failed to deliver clinically useful therapeutic interventions. Thus, there is an unmet need to better understand the function of different HDL particles. Targeted, high-resolution lipoproteomics provides an innovative approach to studying the kinetics of HDL particles. In this commentary, we discuss the development of an informatics platform for increased throughput and highlight how this approach delivers the potential for novel, hybrid instrument technologies to inform clinical dyslipidemia studies.

High-density lipoproteins in high resolution: Will proteomics solve the paradox for cardiovascular risk?

Routine apolipoprotein (apo) measurements for cardiovascular disease (CVD) are restricted to apoA-I and apoB. Here, the authors measured an unprecedented range of apolipoproteins in a prospective, population-based study and relate their plasma levels to risk of CVD.

Article	Year
Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veins. Cardiovascular research\| PubMed ID: 27068509	2016
Optimization of Platelet-Derived Growth Factor Receptor (PDGFR) Inhibitors for Duration of Action, as an Inhaled Therapy for Lung Remodeling in Pulmonary Arterial Hypertension. Journal of medicinal chemistry\| PubMed ID: 27502700	2016
Caveats of Untargeted Metabolomics for Biomarker Discovery. Journal of the American College of Cardiology\| PubMed ID: 27634120	2016
High-density lipoproteins in high resolution: Will proteomics solve the paradox for cardiovascular risk? Proteomics\| PubMed ID: 28067027	2017
Very-Low-Density Lipoprotein-Associated Apolipoproteins Predict Cardiovascular Events and Are Lowered by Inhibition of APOC-III. Journal of the American College of Cardiology\| PubMed ID: 28209220	2017

Ferheen Baig

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