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Article ; Online: Protein glycosylation in cardiovascular health and disease.

Chatham, John C / Patel, Rakesh P

2024

Abstract: Protein glycosylation, which involves the attachment of carbohydrates to proteins, is one of the most abundant protein co-translational and post-translational modifications. Advances in technology have substantially increased our knowledge of the ... ...

Abstract	Protein glycosylation, which involves the attachment of carbohydrates to proteins, is one of the most abundant protein co-translational and post-translational modifications. Advances in technology have substantially increased our knowledge of the biosynthetic pathways involved in protein glycosylation, as well as how changes in glycosylation can affect cell function. In addition, our understanding of the role of protein glycosylation in disease processes is growing, particularly in the context of immune system function, infectious diseases, neurodegeneration and cancer. Several decades ago, cell surface glycoproteins were found to have an important role in regulating ion transport across the cardiac sarcolemma. However, with very few exceptions, our understanding of how changes in protein glycosylation influence cardiovascular (patho)physiology remains remarkably limited. Therefore, in this Review, we aim to provide an overview of N-linked and O-linked protein glycosylation, including intracellular O-linked N-acetylglucosamine protein modification. We discuss our current understanding of how all forms of protein glycosylation contribute to normal cardiovascular function and their roles in cardiovascular disease. Finally, we highlight potential gaps in our knowledge about the effects of protein glycosylation on the heart and vascular system, highlighting areas for future research.
Language	English
Publishing date	2024-03-18
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2490375-9
ISSN	1759-5010 ; 1759-5002
ISSN (online)	1759-5010
ISSN	1759-5002
DOI	10.1038/s41569-024-00998-z
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Article ; Online: SOD2 acetylation and deacetylation: Another tale of Jekyll and Hyde in cancer.

Hjelmeland, Anita B / Patel, Rakesh P

Proceedings of the National Academy of Sciences of the United States of America

2019 Volume 116, Issue 47, Page(s) 23376–23378

MeSH term(s)	Acetylation ; Breast Neoplasms ; Cellular Reprogramming ; Humans ; Lysine ; Sirtuin 3
Chemical Substances	Sirtuin 3 (EC 3.5.1.-) ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2019-11-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1916214116
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Article ; Online: Things We "kNOw" and Do Not "kNOw" about Pulmonary Hypertension.

Barnes, Jarrod W / Patel, Rakesh P

American journal of respiratory and critical care medicine

2018 Volume 198, Issue 2, Page(s) 151–152

MeSH term(s)	Animals ; Hypertension, Pulmonary ; Hypoxia ; Mice ; Nitric Oxide Synthase
Chemical Substances	Nitric Oxide Synthase (EC 1.14.13.39)
Language	English
Publishing date	2018-03-27
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.201803-0424ED
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Article ; Online: Selective Recruitment of Monocyte Subsets by Endothelial N-Glycans.

Regal-McDonald, Kellie / Patel, Rakesh P

The American journal of pathology

2020 Volume 190, Issue 5, Page(s) 947–957

Abstract: Monocyte rolling, adhesion, and transmigration across the endothelium are mediated by specific interactions between surface adhesion molecules. This process is fundamental to innate immunity and to inflammatory disease, including atherosclerosis, where ... ...

Abstract	Monocyte rolling, adhesion, and transmigration across the endothelium are mediated by specific interactions between surface adhesion molecules. This process is fundamental to innate immunity and to inflammatory disease, including atherosclerosis, where monocyte egress into the intimal space is central to formation of fatty plaques. Monocytes are a heterogeneous population of three distinct subsets of cells, all of which play different roles in atherosclerosis progression. However, it is not well understood how interactions between different monocyte subsets and the endothelium are regulated. Furthermore, it is appreciated that endothelial adhesion molecules are heavily N-glycosylated, but beyond regulating protein trafficking to the cell surface, whether and if so how these N-glycans contribute to monocyte recruitment is not known. This review discusses how changes in endothelial N-glycosylation may impact vascular and monocytic inflammation. It will also discuss how regulating N-glycoforms on the endothelial surface may allow for the recruitment of specific monocyte subsets to sites of inflammation, and how further understanding in this area may lead to the development of glyco-specific therapeutics in the treatment of cardiovascular disease.
MeSH term(s)	Animals ; Cell Adhesion Molecules/metabolism ; Endothelial Cells/metabolism ; Glycosylation ; Humans ; Leukocyte Rolling/physiology ; Monocytes/metabolism ; Polysaccharides/metabolism
Chemical Substances	Cell Adhesion Molecules ; Polysaccharides
Language	English
Publishing date	2020-02-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.1016/j.ajpath.2020.01.006
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Article: Clustering Patients With Gout Based on Comorbidities and Biomarkers: A Cross-Sectional Study.

Alduraibi, Fatima K / Saleem, Mohammad / Ricart, Karina / Patel, Rakesh P / Szalai, Alexander J / Singh, Jasvinder A

The Journal of rheumatology

2022 Volume 50, Issue 6, Page(s) 817–826

Abstract: Objective: This single-center clinical study identifies clusters of different phenotypes and pathophysiology subtypes of patients with gout and associated comorbidities.: Methods: Patients clinically diagnosed with gout were enrolled between January ... ...

Abstract	Objective: This single-center clinical study identifies clusters of different phenotypes and pathophysiology subtypes of patients with gout and associated comorbidities. Methods: Patients clinically diagnosed with gout were enrolled between January 2018 and December 2019. Hierarchical cluster analyses were performed using clinical data or biological markers, inflammatory markers, and oxidative stress pathway metabolites assayed from serum and plasma samples. Subgroup clusters were compared using ANOVA for continuous data and chi-square tests for categorical data. Results: Hierarchical cluster analysis identified 3 clusters. Cluster 1 (C1; n = 24) comprised dyslipidemia, hypertension, and early-onset gout, without tophi. Cluster 2 (C2; n = 25) comprised hypertension, dyslipidemia, nephrolithiasis, and obesity. Cluster 3 (C3; n = 39) comprised multiple comorbidities and tophi. Post hoc comparisons of data obtained from samples of patients in C1, C2, and C3 revealed significant differences in the levels of oxidative stress and inflammation-related markers, including 3-nitrotyrosine, tumor necrosis factor, C-reactive protein, interleukin (IL) 1β, IL-6, platelet-derived growth factor (PDGF)-AA, and PDGF-BB. Reclustering patients based on all markers as well as on the biological markers that significantly differed among the initial clusters identified similar clusters. Conclusion: Oxidative stress and inflammatory marker levels may affect the development and clinical manifestations (ie, clinical phenotypes) of gout. Measuring oxidative stress and levels of inflammatory cytokines is a potential adjunctive tool and biomarker for early identification and management of gout.
MeSH term(s)	Humans ; Cross-Sectional Studies ; Gout/diagnosis ; Gout/epidemiology ; Hypertension/complications ; Dyslipidemias ; Cluster Analysis ; Biomarkers ; Hyperuricemia/complications
Chemical Substances	Biomarkers
Language	English
Publishing date	2022-12-15
Publishing country	Canada
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	194928-7
ISSN	1499-2752 ; 0315-162X
ISSN (online)	1499-2752
ISSN	0315-162X
DOI	10.3899/jrheum.220635
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Zs.A 1168: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Tri-iodide and vanadium chloride based chemiluminescent methods for quantification of nitrogen oxides.

Basu, Swati / Ricart, Karina / Gladwin, Mark T / Patel, Rakesh P / Kim-Shapiro, Daniel B

Nitric oxide : biology and chemistry

2022 Volume 121, Page(s) 11–19

Abstract: Nitric Oxide (NO) is an important signaling molecule that plays roles in controlling vascular tone, hemostasis, host defense, and many other physiological functions. Low NO bioavailability contributes to pathology and NO administration has therapeutic ... ...

Abstract	Nitric Oxide (NO) is an important signaling molecule that plays roles in controlling vascular tone, hemostasis, host defense, and many other physiological functions. Low NO bioavailability contributes to pathology and NO administration has therapeutic potential in a variety of diseases. Thus, accurate measurements of NO bioavailability and reactivity are critical. Due to its short lifetime in vivo and many in vitro conditions, NO bioavailability and reactivity are often best determined by measuring NO congeners and metabolites that are more stable. Chemiluminescence-based detection of NO following chemical reduction of these compounds using the tri-iodide and vanadium chloride methods have been widely used in a variety of clinical and laboratory studies. In this review, we describe these methods used to detect nitrite, nitrate, nitrosothiols and other species and discuss limitations and proper controls.
MeSH term(s)	Chlorides/chemistry ; Humans ; Iodides/chemistry ; Luminescent Measurements ; Nitrogen Oxides/analysis ; Vanadium/chemistry
Chemical Substances	Chlorides ; Iodides ; Nitrogen Oxides ; Vanadium (00J9J9XKDE)
Language	English
Publishing date	2022-02-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1362794-6
ISSN	1089-8611 ; 1089-8603
ISSN (online)	1089-8611
ISSN	1089-8603
DOI	10.1016/j.niox.2022.01.006
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Article ; Online: Losing control over adenosine 5'-triphosphate release: implications for the red blood cell storage lesion.

Patel, Rakesh P

Critical care medicine

2011 Volume 39, Issue 11, Page(s) 2573–2574

MeSH term(s)	Adenosine Triphosphate/biosynthesis ; Animals ; Blood Transfusion ; Endothelial Cells/physiology ; Erythrocytes/physiology ; Humans
Chemical Substances	Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2011-10-12
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	197890-1
ISSN	1530-0293 ; 0090-3493
ISSN (online)	1530-0293
ISSN	0090-3493
DOI	10.1097/CCM.0b013e31822a55fa
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Article ; Online: There is blood in the water: hemolysis, hemoglobin, and heme in acute lung injury.

Gaggar, Amit / Patel, Rakesh P

American journal of physiology. Lung cellular and molecular physiology

2016 Volume 311, Issue 4, Page(s) L714–L718

Abstract: The major role of red blood cells (RBCs) is to deliver oxygen and remove carbon dioxide within organisms through the unique properties of hemoglobin. Although beneficial within RBCs, when outside hemoglobin and its breakdown products (heme, iron) induce ... ...

Abstract	The major role of red blood cells (RBCs) is to deliver oxygen and remove carbon dioxide within organisms through the unique properties of hemoglobin. Although beneficial within RBCs, when outside hemoglobin and its breakdown products (heme, iron) induce proinflammatory responses affecting various cellular responses. Although these effects are considered to be prominent in disorders with increased hemolysis, recent evidence suggests that this process may be active in nonhemolytic disorders such as acute lung injury/acute respiratory distress syndrome. This perspectives article focuses on data related to red cell products in nonhemolytic disorders and the potential to target these factors in acute lung injury/acute respiratory distress syndrome.
MeSH term(s)	Acute Lung Injury/blood ; Animals ; Biomarkers/blood ; Erythrocytes ; Heme/metabolism ; Hemoglobins/metabolism ; Hemolysis ; Humans ; Respiratory Distress Syndrome, Adult/blood
Chemical Substances	Biomarkers ; Hemoglobins ; Heme (42VZT0U6YR)
Language	English
Publishing date	2016-08-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1013184-x
ISSN	1522-1504 ; 1040-0605
ISSN (online)	1522-1504
ISSN	1040-0605
DOI	10.1152/ajplung.00312.2016
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Article ; Online: Red blood cell transfusion and its effect on microvascular dysfunction in shock states.

Weinberg, Jordan A / Patel, Rakesh P

Best practice & research. Clinical anaesthesiology

2016 Volume 30, Issue 4, Page(s) 491–498

Abstract: Among critically ill patients, red blood cell (RBC) transfusion is often prescribed for anemia in the absence of active or recent bleeding. The failure of RBC transfusion to improve physiological parameters and clinical outcomes in this setting may be ... ...

Abstract	Among critically ill patients, red blood cell (RBC) transfusion is often prescribed for anemia in the absence of active or recent bleeding. The failure of RBC transfusion to improve physiological parameters and clinical outcomes in this setting may be explained by current understanding of the relationship between the RBCs and the microcirculation. It is now evident that the circulating RBCs contribute to microcirculatory hypoxic vasodilation by regulated nitric oxide (NO)-dependent vasodilation, thereby facilitating delivery of oxygen to oxygen-deprived tissue. The structural and functional changes in RBCs during storage, collectively known as the storage lesion, result in circulating RBCs that may not function as expected after transfusion. In recent years, there has been a significant focus on the dysfunctional interaction between stored RBCs and the microcirculation, with emphasis on understanding the mechanisms that drive erythrocyte NO-mediated vasodilation. The development of technology that allows noninvasive observation of the microcirculation in humans has allowed for direct observation of the microcirculation immediately before and after RBC transfusion. The current understanding of RBC NO-mediated vasodilation and the results of direct observation of the microcirculation in the setting of RBC transfusion are reviewed.
MeSH term(s)	Anemia/physiopathology ; Anemia/therapy ; Erythrocyte Transfusion ; Humans ; Microcirculation ; Shock/physiopathology ; Shock/therapy
Language	English
Publishing date	2016-12
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2028818-9
ISSN	1878-1608 ; 1521-6896 ; 1753-3740
ISSN (online)	1878-1608 ; 1521-6896
ISSN	1753-3740
DOI	10.1016/j.bpa.2016.10.005
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Article ; Online: Supplemental nitrite increases choroidal neovascularization in mice.

Qi, Xiaoping / Ricart, Karina / Ahmed, Khandaker A / Patel, Rakesh P / Boulton, Michael E

Nitric oxide : biology and chemistry

2021 Volume 117, Page(s) 7–15

Abstract: Low doses of nitrite, close to physiological levels, increase blood flow in normal and ischemic tissues through a nitric oxide (NO) dependent mechanism. Given that nitrite therapy and dietary supplementation with vegetables high in nitrate (e.g. beets) ... ...

Abstract	Low doses of nitrite, close to physiological levels, increase blood flow in normal and ischemic tissues through a nitric oxide (NO) dependent mechanism. Given that nitrite therapy and dietary supplementation with vegetables high in nitrate (e.g. beets) are gaining popularity we decided to determine if low doses of nitrite impact the development of choroidal neovascularization (CNV), a key feature of wet age related macular degeneration (AMD). Sodium nitrite (at 50 mg/L, 150 mg/L, and 300 mg/L), nitrate (1 g/L) or water alone were provided in the drinking water of C57BL/6 J mice aged 2 or 12 months. Mice were allowed to drink ad libitum for 1 week at which time laser-induced choroidal neovascularization (L-CNV) was induced. The mice continued to drink the supplemented water ad libitum for a further 14 days at which point optical coherence tomography (OCT) was performed to determine the volume of the CNV lesion. Blood was drawn to determine nitrite and nitrate levels and eyes taken for histology. CNV volume was 2.86 × 10
MeSH term(s)	Animals ; Choroidal Neovascularization/chemically induced ; Female ; Macular Degeneration ; Mice ; Mice, Inbred C57BL ; Nitrates/blood ; Nitrites/administration & dosage ; Nitrites/adverse effects ; Nitrites/blood
Chemical Substances	Nitrates ; Nitrites
Language	English
Publishing date	2021-09-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1362794-6
ISSN	1089-8611 ; 1089-8603
ISSN (online)	1089-8611
ISSN	1089-8603
DOI	10.1016/j.niox.2021.09.005
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