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Cardiovascular System, Extracellular Matrix Research, Atherosclerosis
1. May 2020

Exploring the Role of Extracellular Matrix Proteins to Develop Biomarkers of Plaque Vulnerability and Outcome

Cardiovascular disease (CVD) is the most common cause of death in industrialized countries. One underlying cause is atherosclerosis, which is a systemic disease characterized by plaques of retained lipids, inflammatory cells, apoptotic cells, calcium and extracellular matrix (ECM) proteins in the ar…

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Extracellular Matrix Research, Cardiovascular System
20. Mar 2020

Atrial Fibrillation and Cardiac Fibrosis: A Review on the Potential of Extracellular Matrix Proteins as Biomarkers

The involvement of fibrosis as an underlying pathology in heart diseases is becoming increasingly clear. In recent years, fibrosis has been granted a causative role in heart diseases and is now emerging as a major contributor to Atrial Fibrillation (AF) pathogenesis. AF is the most common arrhythmia…

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Cardiovascular System
17. Jan 2020

Atrial fibrillation is associated with lean body mass in postmenopausal women.

This study investigated the association between body composition and risk of atrial fibrillation (AF) in postmenopausal women. In a retrospective analysis we assessed data from 5704 postmenopausal women (age 70.7 ± 6.5 yrs.) who in 1999-2001 participated in The Prospective Epidemiological Risk Facto…

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Cardiovascular System, Central Nervous System
6. Nov 2019

A caspase-6-cleaved fragment of Glial Fibrillary Acidic Protein as a potential serological biomarker of CNS injury after cardiac arrest.

Blood levels of Glial Fibrillary Acidic protein (GFAP) reflect processes associated with different types of CNS injury. Evidence suggests that GFAP is cleaved by caspases during CNS injury, hence positioning GFAP fragments as potential biomarkers of injury-associated processes. We set out to develop…

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Endocrinology, Type 1-Diabetes, Renal System, Cardiovascular System
13. Sep 2019

Markers of Collagen Formation and Degradation Reflect Renal Function and Predict Adverse Outcomes in Patients With Type 1 Diabetes.

OBJECTIVE:
Patients with type 1 diabetes (T1D) have a higher risk of developing chronic kidney disease, cardiovascular events (CVEs), and mortality than the general population. We hypothesized that two previously published biomarkers, namely PRO-C6, a biomarker of collagen type VI formation, and C3…

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Cardiovascular System, Respiratory System
17. May 2019

Pressure overload induced right ventricular remodeling is not attenuated by the anti-fibrotic agent pirfenidone

Cardiac fibrosis contributes to the development of heart failure in pulmonary hypertension. We aimed to assess the development of fibrosis and the effects of treatment with the anti-fibrotic agent pirfenidone in pressure overload induced right ventricular (RV) failure. Wistar rat weanlings were rand…

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Authors:

  • Andersen S,
  • Axelsen JB,
  • Ringgaard S,
  • Nyengaard JR,
  • Holm Nielsen S,
  • Genovese F,
  • Karsdal MA,
  • Hyldebrandt JA,
  • Sørensen CB,
  • de Man FS,
  • Jan Bogaard H,
  • Nielsen-kudsk JE,
  • Andersen A,
Cardiovascular System, Myocardial Fibrosis, Acute Myocardial Infarct, Extracellular Matrix Research
19. Nov 2018

Cathepsin K-deficiency impairs mouse cardiac function after myocardial infarction.

BACKGROUND:
Extracellular matrix metabolism and cardiac cell death participate centrally in myocardial infarction (MI). This study tested the roles of collagenolytic cathepsin K (CatK) in post-MI left ventricular remodeling.

METHODS AND RESULTS:
Patients with acute MI had higher plasma CatK lev…

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Authors:

  • Fang W,
  • He A,
  • Xiang MX,
  • Lin Y,
  • Wang Y,
  • Li J,
  • Yang C,
  • Zhang X,
  • Liu CL,
  • Sukhova GK,
  • Barascuk N,
  • Larsen L,
  • Karsdal MA,
  • Libby P,
  • Shi GP,
Cardiovascular System, Atherosclerosis
6. Nov 2018

Markers of Basement Membrane Remodeling Are Associated With Higher Mortality in Patients With Known Atherosclerosis.

Background Patients with atherosclerosis have a high risk of cardiovascular events and death. Atherosclerosis is characterized by accumulation of lipids, cells and extracellular matrix proteins in the intima. We hypothesized that dysregulated remodeling of the basement membrane proteins may be assoc…

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Cardiovascular System
11. Sep 2018

Cardiac magnetic resonance using late gadolinium enhancement and atrial T1 mapping predicts poor outcome in patients with atrial fibrillation after catheter ablation therapy

To determine the pre-procedural value of different fibrotic biomarkers and comprehensive cardiac magnetic resonance (CMR) for the prediction of poor response to ablation therapy in patients with atrial fibrillation (AF). Left atrial (LA) late gadolinium enhancement (LGE) and native LA T1 relaxation …

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Authors:

  • Luetkens JA,
  • Wolpers AC,
  • Beiert T,
  • Kuetting D,
  • Dabir D,
  • Homsi R,
  • Meemdermann H,
  • Day'e NA,
  • Knappe V,
  • Karsdal MA,
  • Nielsen SH,
  • Genovese F,
  • Stöckjgt F,
  • Linhart M,
  • Thomas D,
  • Nickenig G,
  • Schild HH,
  • Schrickel JW,
  • Andrié RP,
Cardiovascular System, Atherosclerosis, Extracellular Matrix Research, Biomarker position
28. Aug 2018

A biomarker of collagen type I degradation is associated with cardiovascular events and mortality in patients with atherosclerosis.

OBJECTIVE:
Atherosclerosis is characterized by accumulation of lipids, cells and extracellular matrix (ECM) proteins in the arterial wall. Collagen type I (COL1), a component of the arterial ECM, is cleaved by matrix metalloproteinases (MMPs) and known to be remodelled in atherosclerosis. We explor…

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Extracellular Matrix Research, Atherosclerosis
31. Mar 2018

Assessment of extracellular matrix-related biomarkers in patients with lower extremity artery disease

BACKGROUND:
The prevalence of lower extremity artery disease (LEAD) is high (20%-25%) in the population older than 65 years, but patients are seldom identified until the disease is advanced. Circulating markers of disease activity might provide patients with a key opportunity for timely treatment. …

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Authors:

  • Hernández-Aguilera A,
  • Nielsen SH,
  • Bonache C,
  • Fernández-Arroyo S,
  • Martín-Paredero V,
  • Fibla M,
  • Karsdal MA,
  • Genovese F,
  • Menendez JA,
  • Camps J,
  • Joven J,
Cardiovascular System, Extracellular Matrix Research, Myocardial Fibrosis
1. Jan 2018

Accelerated collagen turnover in women with angina pectoris without obstructive coronary artery disease: An iPOWER substudy

AIM:
Collagens are major cardiac extracellular matrix components, known to be actively remodelled and accumulated during diffuse myocardial fibrosis. We evaluated whether accelerated collagen turnover described by neo-epitope biomarkers reflecting collagen formation and degradation separates patie…

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Cardiovascular System, Extracellular Matrix Research
14. Dec 2017

Understanding Cardiac Extracellular Matrix Remodeling to Develop Biomarkers of Myocardial Infarction Outcomes

Cardiovascular Disease (CVD) is the most common cause of death in industrialized countries, and myocardial infarction (MI) is a major CVD with significant morbidity and mortality. Following MI, the left ventricle (LV) undergoes a wound healing response to ischemia that results in extracellular matri…

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Cardiovascular System, Central Nervous System
5. Sep 2017

The Gly16 Allele of the G16R Single Nucleotide Polymorphism in the β2 -Adrenergic Receptor Gene Augments the Glycemic Response to Adrenaline in Humans

Cerebral non-oxidative carbohydrate consumption may be driven by a β2-adrenergic mechanism. This study tested whether the 46G A (G16R) single nucleotide polymorphism of the β2-adrenergic receptor gene (ADRB2) influences the metabolic and cerebrovascular responses to administration of adrenaline. Fo…

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Authors:

  • Rokamp KZ,
  • Staalsø JM,
  • Zaar M,
  • Rasmussen P,
  • Petersen LG,
  • Nielsen RV,
  • Secher NH,
  • Olsen NV,
  • Nielsen HB,
Extracellular Matrix Research, Peripheral Vascular Disease
12. Aug 2017

Non-invasive evaluation of extracellular matrix remodeling in peripheral artery disease

AIM:
Peripheral artery disease (PAD) is a common manifestation of systemic atherosclerosis affecting peripheral arteries. The underlying pathology of PAD are disorganized extracellular matrix (ECM), caused by inflammation and oxidation. Previous studies have demonstrated an important structure dis…

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Cardiovascular System
6. Aug 2017

Low vs. high haemoglobin trigger for transfusion in vascular surgery: protocol for a randomised trial

BACKGROUND:
In patients with cardiovascular disease, guidelines for administration of red blood cells (RBC) are mainly based on studies outside the vascular surgical setting with the recommendation to use a haemoglobin (hb) trigger-level lower than by guidelines from The European Society for Vascul…

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Authors:

  • Shahidi S,
  • Hellemann D,
  • Pedersen OB,
  • Wetterslev J,
  • Nielsen HB,
  • Møller A,
Cardiovascular System, Type 2-Diabetes
17. Jul 2017

Is cardiovascular disease in patients with diabetes associated with serum levels of MMP-2, LOX, and the elastin degradation products ELM and ELM-2?

BACKGROUND:
Diabetes mellitus type 2 (T2DM) is a significant risk factor for the development of cardiovascular diseases (CVDs). In a previous microarray study of internal mammary arteries from patients with and without T2DM, we observed several elastin-related genes with altered mRNA-expression in …

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Cardiovascular System, Central Nervous System
22. Mar 2017

Muscle oxygen saturation increases during head-up tilt-induced (pre)syncope

AIM:
To evaluate whether muscle vasodilatation plays a role for hypotension developed during central hypovolaemia, muscle oxygenation (Sm O2 ) was examined during (pre)syncope induced by head-up tilt (HUT). Skin blood flow (SkBF) and oxygenation (Sskin O2 ) were determined because evaluation of Sm …

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Authors:

  • Lund A,
  • Sørensen H,
  • Jensen TW,
  • Niemann MJ,
  • Olesen ND,
  • Nielsen HB,
  • Olsen NV,
  • Secher NH,
Cardiovascular System, Central Nervous System
15. Nov 2016

Nitrite and S-Nitrosohemoglobin Exchange Across the Human Cerebral and Femoral Circulation: Relationship to Basal and Exercise Blood Flow Responses to Hypoxia

BACKGROUND:
The mechanisms underlying red blood cell (RBC)-mediated hypoxic vasodilation remain controversial, with separate roles for nitrite () and S-nitrosohemoglobin (SNO-Hb) widely contested given their ability to transduce nitric oxide bioactivity within the microcirculation. To establish the…

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Authors:

  • Bailey DM,
  • Rasmussen P,
  • Overgaard M,
  • Evans KA,
  • Bohm AM,
  • Seifert T,
  • Brassard P,
  • Zaar M,
  • Nielsen HB,
  • Raven PB,
  • Secher NH,
Cardiovascular System
30. Oct 2015

Postoperative volume balance: does stroke volume increase in Trendelenburg's position?

In healthy humans, stroke volume (SV) and cardiac output (CO) do not increase with expansion of the central blood volume by head-down tilt or administration of fluid. Here, we exposed 85 patients to Trendelenburg's position about one hour after surgery while cardiovascular variables were determined …

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Authors:

  • Frost H,
  • Mortensen CR,
  • Secher NH,
  • Nielsen HB,
Cardiovascular System, Atherosclerosis
21. Jun 2013

Acute Myocardial Infarction and Pulmonary Diseases Result in Two Different Degradation Profiles of Elastin as Quantified by Two Novel ELISAs

BACKGROUND:
Elastin is a signature protein of the arteries and lungs, thus it was hypothesized that elastin is subject to enzymatic degradation during cardiovascular and pulmonary diseases. The aim was to investigate if different fragments of the same protein entail different information associated…

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Authors:

  • Skjøt-Arkil H,
  • Clausen RE,
  • Rasmussen LM,
  • Wang W,
  • Wang Y,
  • Zheng Q,
  • Mickley H,
  • Saaby L,
  • Diederichsen AC,
  • Lambrechtsen J,
  • Martinez FJ,
  • Hogaboam CM,
  • Han M,
  • Larsen MR,
  • Nawrocki A,
  • Vainer B,
  • Krustrup D,
  • Bjørling-Poulsen M,
  • Karsdal MA,
  • Leeming DJ,
Extracellular Matrix Research, Cardiovascular System, Atherosclerosis
3. Jun 2013

A MMP derived versican neo-epitope is elevated in plasma from patients with atherosclerotic heart disease

Extracellular matrix remodelling is a prerequisite for plaque rupture in atherosclerotic lesion. Versican, an extracellular matrix proteoglycan present in normal and atherosclerotic arteries is a substrate for matrix metalloproteinases (MMPs) present in macrophage rich areas. The aim of the current …

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Cardiovascular System, Atherosclerosis
21. Jan 2013

Atherofibrosis - a unique and common process of the disease pathogenesis of atherosclerosis and fibrosis - lessons for biomarker development

The hallmark of a variety of fibrotic diseases such as liver fibrosis, lung fibrosis, skin fibrosis and atherosclerosis is extensive extracellular matrix remodeling (ECMr) of the disease affected tissue. Inflammation often leads to tissue disruption and destruction, upon which locally released batte…

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Extracellular Matrix Research, Cardiovascular System, Acute Myocardial Infarct
6. Jul 2012

Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker

BACKGROUND:
Titin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension. Levels and functioning of titin have been shown to be affected by cardiac damage. Due to the inherent difficulty of measuring titin levels in vivo in a clinical s…

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Cardiovascular System, Atherosclerosis
10. May 2012

Novel cardiac-specific biomarkers and the cardiovascular continuum

The concept of the cardiovascular continuum, introduced during the early 1990s, created a holistic view of the chain of events connecting cardiovascular-related risk factors with the progressive development of pathological-related tissue remodelling and ultimately, heart failure and death. Understan…

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Authors:

  • Vassiliadis E,
  • Barascuk N,
  • Didangelos A,
  • Karsdal MA,
Cardiovascular System, Atherosclerosis
10. Feb 2012

Tumor necrosis factor-α and receptor activator of nuclear factor-κB ligand augment human macrophage foam-cell destruction of extracellular matrix through protease-mediated processes

By secreting proteases such as cathepsins and matrix metalloproteinases (MMPs), macrophage foam cells may be a major cause of ruptured atherosclerotic plaques. The aims of the present study were to investigate in vitro role of human macrophage foam cells in degrading type I collagen, a major compone…

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Cardiovascular System, Abdominal Aortic Aneurysm
11. Dec 2011

Abdominal aortic calcification quantified by the Morphological Atherosclerotic Calcification Distribution (MACD) index is associated with features of the metabolic syndrome

BACKGROUND:
Abdominal aortic calcifications (AAC) predict cardiovascular mortality. A new scoring model for AAC, the Morphological Atherosclerotic Calcification Distribution (MACD) index may contribute with additional information to the commonly used Aortic Calcification Severity (AC24) score, when…

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Cardiovascular System, Atherosclerosis
11. Jul 2011

Development and validation of an enzyme-linked immunosorbent assay for the quantification of a specific MMP-9 mediated degradation fragment of type III collagen--A novel biomarker of atherosclerotic plaque remodeling

Degradation of collagen in the arterial wall by matrix metalloproteinases is the hallmark of atherosclerosis. We have developed an ELISA for the quantification of type III collagen degradation mediated by MMP-9 in urine.

DESIGN AND METHODS:
A monoclonal antibody targeting a specific MMP-9 genera…

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Authors:

  • Barascuk N,
  • Vassiliadis E,
  • Larsen L,
  • Wang J,
  • Zheng Q,
  • Xing R,
  • Cao Y,
  • Crespo C,
  • Lapret I,
  • Sabatini M,
  • Villeneuve N,
  • Vilaine JP,
  • Rasmussen LM,
  • Register TC,
  • Karsdal MA,
Cardiovascular System, Atherosclerosis
11. Jun 2011

Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice

AIM:
Arterial extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs) is one of the major hallmarks of atherosclerosis. Mimecan, also known as osteoglycin has been implicated in the integrity of the ECM. This study assessed the validity of an enzyme-linked immunosorbent assay (ELI…

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Authors:

  • Barascuk N,
  • Vassiliadis E,
  • Zheng Q,
  • Wang Y,
  • Wang W,
  • Larsen L,
  • Rasmussen LM,
  • Karsdal MA,
Cardiovascular System, Atherosclerosis
10. Nov 2010

Distribution, size, shape, growth potential and extent of abdominal aortic calcified deposits predict mortality in postmenopausal women

Aortic calcification is a major risk factor for death from cardiovascular disease. We investigated the relationship between mortality and the composite markers of number, size, morphology and distribution of calcified plaques in the lumbar aorta.

METHODS:
308 postmenopausal women aged 48-76 were…

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Cardiovascular System, Atherosclerosis
8. Oct 2010

Macrophage-mediated proteolytic remodeling of the extracellular matrix in atherosclerosis results in neoepitopes: a potential new class of biochemical markers

Worldwide, cardiovascular disease (CVD) is the leading cause of death. Most CVD-related deaths are caused by years of preceding atherogenesis and the extensive development of atherosclerotic plaques, some of which may rupture to cause myocardial infarction. Macrophages are known to have a role in al…

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Authors:

  • Skjøt-Arkil H,
  • Barascuk N,
  • Register T,
  • Karsdal MA,
Cardiovascular System, Atherosclerosis
21. Apr 2010

Human macrophage foam cells degrade atherosclerotic plaques through cathepsin K mediated processes

BACKGROUND:
Proteolytic degradation of Type I Collagen by proteases may play an important role in remodeling of atherosclerotic plaques, contributing to increased risk of plaque rupture.The aim of the current study was to investigate whether human macrophage foam cells degrade the extracellular mat…

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Cardiovascular System, Atherosclerosis
5. Nov 2009

Long-term prevention with hormone-replacement therapy after the menopause: which women should be targeted?

For decades, hormone-replacement therapy (HRT) was considered safe and was the first choice in prevention of postmenopausal osteoporosis induced by estrogen deficiency. Numerous experimental and epidemiological studies further supported a protective effect of exogenous female sex hormones on atherog…

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