Hideyuki Higashi
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View article: A Combined Gas-Phase Separation Strategy for ADP-ribosylated Peptides
A Combined Gas-Phase Separation Strategy for ADP-ribosylated Peptides Open
ADP-ribosylation (ADPr) is a post-translational modification that is best studied using mass spectrometry. Method developments that are permissive with low inputs or baseline levels of protein ribosylation represent the next frontier in th…
View article: Multiomics of Tissue Extracellular Vesicles Identifies Unique Modulators of Atherosclerosis and Calcific Aortic Valve Stenosis
Multiomics of Tissue Extracellular Vesicles Identifies Unique Modulators of Atherosclerosis and Calcific Aortic Valve Stenosis Open
BACKGROUND: Fewer than 50% of patients who develop aortic valve calcification have concomitant atherosclerosis, implying differential pathogenesis. Although circulating extracellular vesicles (EVs) act as biomarkers of cardiovascular disea…
View article: The distinct metabolism between large and small HDL indicates unique origins of human apolipoprotein A4
The distinct metabolism between large and small HDL indicates unique origins of human apolipoprotein A4 Open
Apolipoprotein A4's (APOA4's) functions on HDL in humans are not well understood. A unique feature of APOA4 is that it is an intestinal apolipoprotein secreted on HDL and chylomicrons. The goal of this study was to gain a better understand…
View article: Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) Promotes Macrophage Activation via LDL Receptor-Independent Mechanisms
Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) Promotes Macrophage Activation via LDL Receptor-Independent Mechanisms Open
Background: Activated macrophages contribute to the pathogenesis of vascular disease. Vein graft failure is a major clinical problem with limited therapeutic options. PCSK9 (proprotein convertase subtilisin/kexin 9) increases low-density l…
View article: Identifying novel mechanisms of abdominal aortic aneurysm via unbiased proteomics and systems biology
Identifying novel mechanisms of abdominal aortic aneurysm via unbiased proteomics and systems biology Open
Background Abdominal aortic aneurysm (AAA), characterized by a continued expansion of the aorta, leads to rupture if not surgically repaired. Mice aid the study of disease progression and its underlying mechanisms since sequential studies …
View article: A disease-driver population within interstitial cells of human calcific aortic valves identified via single-cell and proteomic profiling
A disease-driver population within interstitial cells of human calcific aortic valves identified via single-cell and proteomic profiling Open
View article: A Novel Spectral Annotation Strategy Streamlines Reporting of Mono-ADP-ribosylated Peptides Derived from Mouse Liver and Spleen in Response to IFN-γ
A Novel Spectral Annotation Strategy Streamlines Reporting of Mono-ADP-ribosylated Peptides Derived from Mouse Liver and Spleen in Response to IFN-γ Open
View article: Integration of Functional Imaging, Cytometry, and Unbiased Proteomics Reveals New Features of Endothelial-to-Mesenchymal Transition in Ischemic Mitral Valve Regurgitation in Human Patients
Integration of Functional Imaging, Cytometry, and Unbiased Proteomics Reveals New Features of Endothelial-to-Mesenchymal Transition in Ischemic Mitral Valve Regurgitation in Human Patients Open
Background: Following myocardial infarction, mitral regurgitation (MR) is a common complication. Previous animal studies demonstrated the association of endothelial-to-mesenchymal transition (EndMT) with mitral valve (MV) remodeling. Never…
View article: Elastogenesis Correlates With Pigment Production in Murine Aortic Valve Leaflets
Elastogenesis Correlates With Pigment Production in Murine Aortic Valve Leaflets Open
Objective: Aortic valve (AV) leaflets rely on a precise extracellular matrix (ECM) microarchitecture for appropriate biomechanical performance. The ECM structure is maintained by valvular interstitial cells (VICs), which reside within the …
View article: Dynamin-related protein 1 inhibition reduces hepatic PCSK9 secretion
Dynamin-related protein 1 inhibition reduces hepatic PCSK9 secretion Open
Aims Proteostasis maintains protein homeostasis and participates in regulating critical cardiometabolic disease risk factors including proprotein convertase subtilisin/kexin type 9 (PCSK9). Endoplasmic reticulum (ER) remodeling through rel…
View article: ApoC-III is a novel inducer of calcification in human aortic valves
ApoC-III is a novel inducer of calcification in human aortic valves Open
Calcific aortic valve disease (CAVD) occurs when subpopulations of valve cells undergo specific differentiation pathways, promoting tissue fibrosis and calcification. Lipoprotein particles carry oxidized lipids that promote valvular diseas…
View article: CROT (Carnitine O-Octanoyltransferase) Is a Novel Contributing Factor in Vascular Calcification via Promoting Fatty Acid Metabolism and Mitochondrial Dysfunction
CROT (Carnitine O-Octanoyltransferase) Is a Novel Contributing Factor in Vascular Calcification via Promoting Fatty Acid Metabolism and Mitochondrial Dysfunction Open
Objective: Vascular calcification is a critical pathology associated with increased cardiovascular event risk, but there are no Food and Drug Administration-approved anticalcific therapies. We hypothesized and validated that an unbiased sc…
View article: Metabolism of PLTP, CETP, and LCAT on multiple HDL sizes using the Orbitrap Fusion Lumos
Metabolism of PLTP, CETP, and LCAT on multiple HDL sizes using the Orbitrap Fusion Lumos Open
Recent in vivo tracer studies demonstrated that targeted mass spectrometry (MS) on the Q Exactive Orbitrap could determine the metabolism of HDL proteins 100s-fold less abundant than apolipoprotein A1 (APOA1). In this study, we demonstrate…
View article: Annexin A1–dependent tethering promotes extracellular vesicle aggregation revealed with single–extracellular vesicle analysis
Annexin A1–dependent tethering promotes extracellular vesicle aggregation revealed with single–extracellular vesicle analysis Open
Protein-mediated tethering of vesicles in the extracellular matrix contributes to microcalcification formation.
View article: S100A9-RAGE Axis Accelerates Formation of Macrophage-Mediated Extracellular Vesicle Microcalcification in Diabetes Mellitus
S100A9-RAGE Axis Accelerates Formation of Macrophage-Mediated Extracellular Vesicle Microcalcification in Diabetes Mellitus Open
Objective: Vascular calcification is a cardiovascular risk factor and accelerated in diabetes mellitus. Previous work has established a role for calcification-prone extracellular vesicles in promoting vascular calcification. However, the m…
View article: Conserved and Divergent Modulation of Calcification in Atherosclerosis and Aortic Valve Disease by Tissue Extracellular Vesicles
Conserved and Divergent Modulation of Calcification in Atherosclerosis and Aortic Valve Disease by Tissue Extracellular Vesicles Open
Background Fewer than 50% of patients develop calcification of both atherosclerotic plaques and aortic valves, implying differential pathogenesis. While circulating extracellular vesicles (EVs) act as biomarkers of cardiovascular diseases,…
View article: The impact of PARPs and ADP-ribosylation on inflammation and host–pathogen interactions
The impact of PARPs and ADP-ribosylation on inflammation and host–pathogen interactions Open
Poly-adenosine diphosphate-ribose polymerases (PARPs) promote ADP-ribosylation, a highly conserved, fundamental posttranslational modification (PTM). PARP catalytic domains transfer the ADP-ribose moiety from NAD + to amino acid residues o…
View article: Effects of Replacing Dietary Monounsaturated Fat With Carbohydrate on HDL (High-Density Lipoprotein) Protein Metabolism and Proteome Composition in Humans
Effects of Replacing Dietary Monounsaturated Fat With Carbohydrate on HDL (High-Density Lipoprotein) Protein Metabolism and Proteome Composition in Humans Open
Objective: Clinical evidence has linked low HDL (high-density lipoprotein) cholesterol levels with high cardiovascular disease risk; however, its significance as a therapeutic target remains unestablished. We hypothesize that HDLs function…
View article: Standardization of Human Calcific Aortic Valve Disease in vitro Modeling Reveals Passage-Dependent Calcification
Standardization of Human Calcific Aortic Valve Disease in vitro Modeling Reveals Passage-Dependent Calcification Open
Aortic valvular interstitial cells (VICs) isolated from patients undergoing valve replacement are commonly used as in vitro models of calcific aortic valve disease (CAVD). Standardization of VIC calcification, however, has not been …
View article: Uremic Toxin Indoxyl Sulfate Promotes Proinflammatory Macrophage Activation Via the Interplay of OATP2B1 and Dll4-Notch Signaling
Uremic Toxin Indoxyl Sulfate Promotes Proinflammatory Macrophage Activation Via the Interplay of OATP2B1 and Dll4-Notch Signaling Open
Background: Chronic kidney disease (CKD) increases cardiovascular risk. Underlying mechanisms, however, remain obscure. The uremic toxin indoxyl sulfate is an independent cardiovascular risk factor in CKD. We explored the potential impact …
View article: Spatiotemporal Multi-Omics Mapping Generates a Molecular Atlas of the Aortic Valve and Reveals Networks Driving Disease
Spatiotemporal Multi-Omics Mapping Generates a Molecular Atlas of the Aortic Valve and Reveals Networks Driving Disease Open
Background: No pharmacological therapy exists for calcific aortic valve disease (CAVD), which confers a dismal prognosis without invasive valve replacement. The search for therapeutics and early diagnostics is challenging because CAVD pres…
View article: Inside Front Cover: PRM technology enables detection and reliable automated quantification of low tracer incorporation into circulating apolipoproteins for HDL metabolism studies
Inside Front Cover: PRM technology enables detection and reliable automated quantification of low tracer incorporation into circulating apolipoproteins for HDL metabolism studies Open
DOI: 10.1002/pmic.201600085 Metabolism studies traditionally use D3-Leu tracer for endogenous labeling of circulating proteins such as those on lipoproteins (yellow, low density apoB lipoproteins; blue, high density apoA-I lipoproteins or …