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Article ; Online: No guidelines for vascular nerves?

De Mey, Jo G R / Simonsen, Ulf / Aalkjær, Christian

American journal of physiology. Heart and circulatory physiology

2022 Volume 322, Issue 4, Page(s) H681–H682

Language	English
Publishing date	2022-03-24
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00053.2022
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Article ; Online: Vasodilatation: One Question with Many Answers.

Wang, Yu / De Mey, Jo G R

Journal of cardiovascular pharmacology

2021 Volume 78, Issue Suppl 6, Page(s) S1–S2

MeSH term(s)	Animals ; Biological Factors/metabolism ; Congresses as Topic ; Endothelial Cells/metabolism ; Endothelium, Vascular/metabolism ; Endothelium-Dependent Relaxing Factors/metabolism ; Humans ; Membrane Potentials ; Signal Transduction ; Vasodilation
Chemical Substances	Biological Factors ; Endothelium-Dependent Relaxing Factors ; endothelium-dependent hyperpolarization factor
Language	English
Publishing date	2021-11-24
Publishing country	United States
Document type	Editorial ; Introductory Journal Article
ZDB-ID	391970-5
ISSN	1533-4023 ; 0160-2446
ISSN (online)	1533-4023
ISSN	0160-2446
DOI	10.1097/FJC.0000000000001169
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Article ; Online: Sympathetic and Sensory-Motor Nerves in Peripheral Small Arteries.

Aalkjær, Christian / Nilsson, Holger / De Mey, Jo G R

Physiological reviews

2020 Volume 101, Issue 2, Page(s) 495–544

Abstract: Small arteries, which play important roles in controlling blood flow, blood pressure, and capillary pressure, are under nervous influence. Their innervation is predominantly sympathetic and sensory motor in nature, and while some arteries are densely ... ...

Abstract	Small arteries, which play important roles in controlling blood flow, blood pressure, and capillary pressure, are under nervous influence. Their innervation is predominantly sympathetic and sensory motor in nature, and while some arteries are densely innervated, others are only sparsely so. Innervation of small arteries is a key mechanism in regulating vascular resistance. In the second half of the previous century, the physiology and pharmacology of this innervation were very actively investigated. In the past 10-20 yr, the activity in this field was more limited. With this review we highlight what has been learned during recent years with respect to development of small arteries and their innervation, some aspects of excitation-release coupling, interaction between sympathetic and sensory-motor nerves, cross talk between endothelium and vascular nerves, and some aspects of their role in vascular inflammation and hypertension. We also highlight what remains to be investigated to further increase our understanding of this fundamental aspect of vascular physiology.
MeSH term(s)	Animals ; Arteries/innervation ; Humans ; Hypertension/physiopathology ; Motor Neurons/physiology ; Neurotransmitter Agents/physiology ; Sensory Receptor Cells/physiology ; Sympathetic Nervous System/physiology
Chemical Substances	Neurotransmitter Agents
Language	English
Publishing date	2020-12-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	209902-0
ISSN	1522-1210 ; 0031-9333
ISSN (online)	1522-1210
ISSN	0031-9333
DOI	10.1152/physrev.00007.2020
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Article ; Online: The angiotensin AT

Fredgart, Maise H / Leurgans, Thomas M / Stenelo, Martin / Nybo, Mads / Bloksgaard, Maria / Lindblad, Lena / De Mey, Jo G R / Steckelings, U Muscha

Peptides

2023 Volume 164, Page(s) 170990

Abstract: Since the ... ...

Abstract	Since the AT
MeSH term(s)	Humans ; Mice ; Animals ; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology ; Receptors, Thromboxane ; Thromboxanes ; Mice, Inbred C57BL ; Thromboxane A2/pharmacology ; Phenylephrine/pharmacology ; Angiotensins
Chemical Substances	compound 21 (RC2V4W0EYC) ; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid (76898-47-0) ; Receptors, Thromboxane ; Thromboxanes ; Thromboxane A2 (57576-52-0) ; Phenylephrine (1WS297W6MV) ; Angiotensins
Language	English
Publishing date	2023-03-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	769028-9
ISSN	1873-5169 ; 0196-9781
ISSN (online)	1873-5169
ISSN	0196-9781
DOI	10.1016/j.peptides.2023.170990
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Article ; Online: Physiological Consequences of Coronary Arteriolar Dysfunction and Its Influence on Cardiovascular Disease: Diagnostic and Additional Therapeutic Consequences.

De Mey, Jo G R / Bloksgaard, Maria / Aalkjær, Christian

Physiology (Bethesda, Md.)

2019 Volume 34, Issue 2, Page(s) 82–83

MeSH term(s)	Arterioles ; Cardiovascular Diseases ; Heart Diseases ; Humans
Language	English
Publishing date	2019-02-06
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2158667-6
ISSN	1548-9221 ; 1548-9213
ISSN (online)	1548-9221
ISSN	1548-9213
DOI	10.1152/physiol.00053.2018
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Article ; Online: Pericardial delta like non-canonical NOTCH ligand 1 (Dlk1) augments fibrosis in the heart through epithelial to mesenchymal transition.

Jensen, Charlotte Harken / Johnsen, Rikke Helin / Eskildsen, Tilde / Baun, Christina / Ellman, Ditte Gry / Fang, Shu / Bak, Sara Thornby / Hvidsten, Svend / Larsen, Lars Allan / Rosager, Ann Mari / Riber, Lars Peter / Schneider, Mikael / De Mey, Jo / Thomassen, Mads / Burton, Mark / Uchida, Shizuka / Laborda, Jorge / Andersen, Ditte Caroline

Clinical and translational medicine

2024 Volume 14, Issue 2, Page(s) e1565

Abstract: Background: Heart failure due to myocardial infarction (MI) involves fibrosis driven by epicardium-derived cells (EPDCs) and cardiac fibroblasts, but strategies to inhibit and provide cardio-protection remains poor. The imprinted gene, non-canonical ... ...

Abstract	Background: Heart failure due to myocardial infarction (MI) involves fibrosis driven by epicardium-derived cells (EPDCs) and cardiac fibroblasts, but strategies to inhibit and provide cardio-protection remains poor. The imprinted gene, non-canonical NOTCH ligand 1 (Dlk1), has previously been shown to mediate fibrosis in the skin, lung and liver, but very little is known on its effect in the heart. Methods: Herein, human pericardial fluid/plasma and tissue biopsies were assessed for DLK1, whereas the spatiotemporal expression of Dlk1 was determined in mouse hearts. The Dlk1 heart phenotype in normal and MI hearts was assessed in transgenic mice either lacking or overexpressing Dlk1. Finally, in/ex vivo cell studies provided knowledge on the molecular mechanism. Results: Dlk1 was demonstrated in non-myocytes of the developing human myocardium but exhibited a restricted pericardial expression in adulthood. Soluble DLK1 was twofold higher in pericardial fluid (median 45.7 [34.7 (IQR)) μg/L] from cardiovascular patients (n = 127) than in plasma (median 26.1 μg/L [11.1 (IQR)]. The spatial and temporal expression pattern of Dlk1 was recapitulated in mouse and rat hearts. Similar to humans lacking Dlk1, adult Dlk1 Conclusions: Our results suggest that pericardial Dlk1 embraces a, so far, unnoticed role in the heart augmenting cardiac fibrosis through EMT. Monitoring DLK1 levels as well as targeting pericardial DLK1 may thus offer new venues for cardio-protection.
MeSH term(s)	Adult ; Animals ; Humans ; Mice ; Calcium-Binding Proteins/genetics ; Calcium-Binding Proteins/metabolism ; Cicatrix/metabolism ; Cicatrix/pathology ; Epithelial-Mesenchymal Transition/genetics ; Fibrosis ; Ligands ; Mice, Transgenic ; Myocardial Infarction/genetics ; Pericardium/metabolism ; Thorax/pathology
Chemical Substances	Calcium-Binding Proteins ; Dlk1 protein, mouse ; Ligands ; DLK1 protein, human
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2697013-2
ISSN	2001-1326 ; 2001-1326
ISSN (online)	2001-1326
ISSN	2001-1326
DOI	10.1002/ctm2.1565
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Article ; Online: Retinal Vascular Fractal Dimensions and Their Association with Macrovascular Cardiac Disease.

Dinesen, Sebastian / Jensen, Pia S / Bloksgaard, Maria / Blindbæk, Søren Leer / De Mey, Jo / Rasmussen, Lars M / Lindholt, Jes S / Grauslund, Jakob

Ophthalmic research

2021 Volume 64, Issue 4, Page(s) 561–566

Abstract: Introduction: As the only part of the human vasculature, the retina is available for direct, noninvasive inspection. Retinal vascular fractal dimension (DF) is a method to measure the structure of the retinal vascular tree, with higher noninteger values ...

Abstract	Introduction: As the only part of the human vasculature, the retina is available for direct, noninvasive inspection. Retinal vascular fractal dimension (DF) is a method to measure the structure of the retinal vascular tree, with higher noninteger values between 1 and 2 representing a more complex and dense retinal vasculature. Retinal vascular structure has been associated with a variety of systemic diseases, and this study examined the association of DF and macrovascular cardiac disease in a case-control design. Methods: Retinal fundus photos were captured with Topcon TRC-50X in 38 persons that had coronary artery bypass grafting (CABG, cases) and 37 cardiovascular healthy controls. The semiautomatic software VAMPIRE was used to measure retinal DF. Results: Patients with CABG had lower DF of the retinal main venular vessels compared to the control group (1.15 vs. 1.18, p = 0.01). In a multivariable regression model adjusted for gender and age, eyes in the fourth quartile with higher DF were less likely to have CABG compared to patients in the first (OR, 7.20; 95% confidence interval: 1.63-31.86; p = 0.009) and second (OR, 8.25; 95% confidence interval: 1.70-40.01; p = 0.009) quartiles. Conclusions: This study demonstrates that lower complexity of main venular vessels associates with higher risk of having CABG. The research supports the hypothesis that the retinal vascular structure can be used to assess nonocular macrovascular disease.
MeSH term(s)	Fractals ; Fundus Oculi ; Heart Diseases ; Humans ; Retina ; Retinal Vessels
Language	English
Publishing date	2021-01-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	205708-6
ISSN	1423-0259 ; 0030-3747
ISSN (online)	1423-0259
ISSN	0030-3747
DOI	10.1159/000514442
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Article ; Online: Nitric oxide (NO) synthase but not NO, HNO or H

Matthies, Maximilian / Rosenstand, Kristoffer / Nissen, Inger / Muitjens, Stan / Riber, Lars P / De Mey, Jo G R / Bloksgaard, Maria

British journal of pharmacology

2021 Volume 179, Issue 5, Page(s) 1049–1064

Abstract: Background and purpose: Superoxide anions can reduce the bioavailability and actions of endothelium-derived NO. In human resistance-sized arteries, endothelium-dependent vasodilatation can be mediated by H: Experimental approach: Small arteries were ... ...

Abstract	Background and purpose: Superoxide anions can reduce the bioavailability and actions of endothelium-derived NO. In human resistance-sized arteries, endothelium-dependent vasodilatation can be mediated by H Experimental approach: Small arteries were isolated from biopsies of the parietal pericardium of patients undergoing elective cardiothoracic surgery and were studied using immunohistochemical and organ chamber techniques. Key results: NO synthases 1, 2 and 3, superoxide dismutase 1 and catalase proteins were observed in the microvascular wall. Relaxing responses to bradykinin were endothelium dependent. During submaximal depolarization-induced contraction, bradykinin-mediated relaxations were inhibited by inhibitors of NO synthases (NOS) and soluble guanylyl cyclase (sGC) but not by scavengers of NO or HNO, inhibitors of cyclooxygenases, neuronal NO synthase, superoxide dismutase or catalase, or by exogenous catalase. During contraction stimulated by endothelin-1, these relaxations were not reduced by any of these interventions except DETCA, which caused a small reduction. Conclusion and implications: In resistance arteries from patients with cardiovascular disease, endothelium-dependent relaxations seem not to be mediated by NO, HNO or H
MeSH term(s)	Arteries/metabolism ; Bradykinin/pharmacology ; Cardiovascular Diseases ; Catalase ; Endothelium, Vascular/metabolism ; Humans ; Nitric Oxide/metabolism ; Nitric Oxide Synthase ; Soluble Guanylyl Cyclase ; Vasodilation
Chemical Substances	Nitric Oxide (31C4KY9ESH) ; Catalase (EC 1.11.1.6) ; Nitric Oxide Synthase (EC 1.14.13.39) ; Soluble Guanylyl Cyclase (EC 4.6.1.2) ; Bradykinin (S8TIM42R2W)
Language	English
Publishing date	2021-11-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.15712
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Article: Assessing collagen and elastin pressure-dependent microarchitectures in live, human resistance arteries by label-free fluorescence microscopy

Bloksgaard, Maria / Thorsted, Bjarne / Brewer, Jonathan R / De Mey, Jo G. R

Journal of visualized experiments. 2018 Apr. 09, , no. 134

2018

Abstract: The pathogenic contribution of resistance artery remodeling is documented in essential hypertension, diabetes and the metabolic syndrome. Investigations and development of microstructurally motivated mathematical models for understanding the mechanical ... ...

Abstract	The pathogenic contribution of resistance artery remodeling is documented in essential hypertension, diabetes and the metabolic syndrome. Investigations and development of microstructurally motivated mathematical models for understanding the mechanical properties of human resistance arteries in health and disease have the potential to aid understanding how disease and medical treatments affect the human microcirculation. To develop these mathematical models, it is essential to decipher the relationship between the mechanical and microarchitectural properties of the microvascular wall. In this work, we describe an ex vivo method for passive mechanical testing and simultaneous label-free three-dimensional imaging of the microarchitecture of elastin and collagen in the arterial wall of isolated human resistance arteries. The imaging protocol can be applied to resistance arteries of any species of interest. Image analyses are described for quantifying i) pressure-induced changes in internal elastic lamina branching angles and adventitial collagen straightness using Fiji and ii) collagen and elastin volume densities determined using Ilastik software. Preferably all mechanical and imaging measurements are performed on live, perfused arteries, however, an alternative approach using standard video-microscopy pressure myography in combination with post-fixation imaging of re-pressurized vessels is discussed. This alternative method provides users with different options for analysis approaches. The inclusion of the mechanical and imaging data in mathematical models of the arterial wall mechanics is discussed, and future development and additions to the protocol are proposed.
Keywords	arteries ; collagen ; computer software ; diabetes ; digital images ; elastin ; ex vivo studies ; fluorescence microscopy ; humans ; hypertension ; image analysis ; mathematical models ; mechanical properties ; mechanical testing ; medical treatment ; metabolic syndrome ; Fiji
Language	English
Dates of publication	2018-0409
Size	p. e57451.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/57451
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Local IGF Bioactivity Associates with High PAPP-A Activity in the Pericardial Cavity of Cardiovascular Disease Patients.

Hjortebjerg, Rikke / Rasmussen, Lars Melholt / Gude, Mette Faurholdt / Irmukhamedov, Akhmadjon / Riber, Lars P / Frystyk, Jan / De Mey, Jo G R

The Journal of clinical endocrinology and metabolism

2020 Volume 105, Issue 11

Abstract: Objective: Pregnancy-associated plasma protein-A (PAPP-A) has been suggested as a proatherogenic enzyme by its ability to locally increase insulin-like growth factor (IGF) activity through proteolytic cleavage of IGF binding protein-4 (IGFBP-4). ... ...

Abstract	Objective: Pregnancy-associated plasma protein-A (PAPP-A) has been suggested as a proatherogenic enzyme by its ability to locally increase insulin-like growth factor (IGF) activity through proteolytic cleavage of IGF binding protein-4 (IGFBP-4). Recently, stanniocalcin-2 (STC2) was discovered as an inhibitor of PAPP-A. This study aimed to investigate IGFBP-4, PAPP-A, and STC2 as local regulators of IGF bioactivity in the cardiac microenvironment by comparing levels in the pericardial fluid with those in the circulation of patients with cardiovascular disease. Methods: Plasma and pericardial fluid were obtained from 39 patients undergoing elective cardiothoracic surgery, hereof 15 patients with type 2 diabetes. Concentrations of IGF-I, intact and fragmented IGFBP-4, PAPP-A, and STC2 were determined by immunoassays and IGF bioactivity by a cell-based assay. Results: In pericardial fluid, the concentrations of total IGF-I, intact IGFBP-4, and STC2 were 72 ± 10%, 91 ± 5%, and 40 ± 24% lower than in plasma, while PAPP-A was 15 times more concentrated. The levels of the 2 IGFBP-4 fragments generated by PAPP-A and reflecting PAPP-A activity were elevated by more than 25%. IGF bioactivity was 62 ± 81% higher in the pericardial fluid than plasma. Moreover, pericardial fluid levels of both IGFBP-4 fragments correlated with the concentration of PAPP-A and with the bioactivity of IGF. All protein levels were similar in pericardial fluid from nondiabetic and diabetic subjects. Conclusions: PAPP-A increases IGF bioactivity by cleavage of IGFBP-4 in the pericardial cavity of cardiovascular disease patients. This study provides evidence for a distinct local activity of the IGF system, which may promote cardiac dysfunction and coronary atherosclerosis.
MeSH term(s)	Aged ; Cardiovascular Diseases/metabolism ; Cardiovascular Diseases/surgery ; Coronary Artery Bypass ; Diabetes Mellitus, Type 2/metabolism ; Glycoproteins/metabolism ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Male ; Middle Aged ; Pericardial Fluid/metabolism ; Pericardium/metabolism ; Pregnancy-Associated Plasma Protein-A/metabolism ; Somatomedins/metabolism
Chemical Substances	Glycoproteins ; Intercellular Signaling Peptides and Proteins ; STC2 protein, human ; Somatomedins ; Pregnancy-Associated Plasma Protein-A (EC 3.4.24.-)
Language	English
Publishing date	2020-09-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgaa617
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