Quantitative Proteome Analysis Reveals Increased Content of Basement Membrane Proteins in Arteries From Patients With Type 2 Diabetes Mellitus and Lower Levels Among Metformin Users

Preil, Simone Rørdam; Kristensen, Lars; Beck, Hans Christian; Jensen, Peter Bjødstrup; Nielsen, Patricia Switten; Steiniche, Torben; Bjørling-Poulsen, Marina; Larsen, Martin R.; Hansen, Morten Hartvig; Rasmussen, Lars Melholt

doi:10.1161/circgenetics.115.001165

Cited by 37 publications

(45 citation statements)

References 50 publications

(52 reference statements)

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“…This muscular artery has dimensions comparable to the coronary arteries and has proven to be a suitable model for investigations of the associations between various clinical conditions and arterial pathology; for example, in relation to fibrosis, diabetes, and medication, etc. [13,14,15,16]. The artery is usually free of atherosclerosis and intimal lesions, and the present results therefore reflect associations between the iron metabolism and generalized arterial structure and biochemistry.…”

Section: Discussionsupporting

confidence: 52%

Arterial Iron Content Is Increased in Patients with High Plasma Ferritin Levels

Madsen

Pedersen²,

Kidholm³

et al. 2016

J Vasc Res

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The association between increased amounts of stored iron and development of cardiovascular disease (CVD) has been recognized for many years. However, basic information on iron content in human arteries is limited. We envision that associations between body iron content and CVD are based on the accumulation of iron in the arteries, possibly leading to the dysfunction of cellular biochemical pathways. This study addresses the very fundamental question of whether there is a relation between body iron content and the level of iron accumulated in arterial tissue. The iron content in human nonatherosclerotic artery samples from patients with high and low body-iron contents estimated from the plasma ferritin concentration were determined by inductively coupled plasma mass spectroscopy in tissue extracts and by histological staining, using a modified Perls reaction to display iron deposits. We found that the arteries contained small but measurable levels of iron. The iron content was significantly higher in tissue from patients with high plasma ferritin (p = 0.026). Histological staining showed the presence of iron deposits. Our results suggest that iron does accumulate in arterial tissue in accordance to the level of stored body iron. Further studies are needed on the distribution of iron in excess to explain the relationship between stored iron and the development of atherosclerosis.

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Section: Discussionsupporting

confidence: 52%

Arterial Iron Content Is Increased in Patients with High Plasma Ferritin Levels

Madsen

Pedersen²,

Kidholm³

et al. 2016

J Vasc Res

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“…The partial Spearman rank correlations were adjusted for smoking and diabetes mellitus status and intervention-size. Fisher exact test was used to test whether the distribution of significant versus nonsignificant correlated plasma-, ECM-and cytoskeletal-proteins were random, as previously described in Preil et al 22,23 Statistics were performed using Microsoft Excel, STATA 13. …”

Section: Methodsmentioning

confidence: 99%

Abdominal Aortic Aneurysms Growth Is Associated With High Concentrations of Plasma Proteins in the Intraluminal Thrombus and Diseased Arterial Tissue

Andersen

Lindholt

Urbonavičius

et al. 2018

ATVB

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Objective-Porosity of the intraluminal thrombus (ILT) is believed to convey biologically active components from the bloodstream toward the aneurismal wall. Accumulation of molecules in the abdominal aortic aneurysmatic tissue may influence vascular protein turnover and regulate abdominal aortic aneurysm growth. We sought to identify proteins with concentrations in the ILT and the abdominal aortic aneurysm wall which associate with aneurysmal expansion rate. Approach and Results-Proteomic analysis by liquid chromatography tandem-mass spectrometry of separated wall and ILT samples was correlated with preoperative aneurysmal growth rate in 24 individuals operated electively for infrarenal abdominal aortic aneurysm. The median preoperative growth rate was 3.8 mm/y (interquartile range, 3) and the mean observational time was 3.3±1.7 years. Plasma components dominated the group of proteins with tissue concentrations, which correlate positively with growth rates (P<0.001, Fisher exact test, both in the ILT and the wall). In contrast, in the wall and thrombus samples, ECM (extracellular matrix) proteins were significantly more prevalent in the group of proteins with negative correlations to growth rates (P<0.05, Fisher exact test). Similarly, a long series of proteins, related to cellular functions correlated negatively to growth rates. Conclusions-When the preoperative aneurysmatic growth rate has been high, the concentration of many plasma proteins residing in the ILT and the aneurysmatic tissue is also high, compatible with the hypothesis of increased tissue porosity and accumulation of plasma components as a driver of aneurysm expansion. Moreover, many matrix and cellular proteins which are found in high concentrations in slower-growing aneurysms provides new knowledge about potential treatment targets. Visual Overview-An online visual overview is available for this article.

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“…The authors found an increased deposition of the basement membrane components alpha-1 and alpha-2 type IV collagen, gamma-1 and beta-2 laminin in diabetic patients [10]. …”

Section: Discussionmentioning

confidence: 99%

“…Based on previous studies with vascular tissue obtained from CABG [9, 10], the total estimated number of patients necessary for this study is 50, equally divided in DM and NDM.…”

Section: Methodsmentioning

confidence: 99%

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Research proposal: inflammation and oxidative stress in coronary artery bypass surgery graft: comparison between diabetic and non-diabetic patients

et al. 2018

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BackgroundDiabetes mellitus patients (DM) have more severe progression of atherosclerotic disease than non-diabetic (NDM) individuals. In situ inflammation and oxidative stress are key points in the pathophysiology of atherosclerosis, a concept largely based on animal model research. There are few studies comparing inflammation and oxidative stress parameters in medium-sized arteries between DM and NDM patients. A fragment of the internal mammary artery used in coronary artery bypass grafting (CABG) will be employed for this purposeObjectiveTo assess the expression of inflammatory markers tumor necrosis factor-α, transforming growth factor-β1, nuclear factor kappa B, the enzymes superoxide dismutase, and catalase in the vascular wall of the arterial graft used in CABG, comparing DM and NDM patientsResultsThe present study will add information to the vascular degenerative processes occurring in diabetic patients.

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Quantitative Proteome Analysis Reveals Increased Content of Basement Membrane Proteins in Arteries From Patients With Type 2 Diabetes Mellitus and Lower Levels Among Metformin Users

Cited by 37 publications

References 50 publications

Arterial Iron Content Is Increased in Patients with High Plasma Ferritin Levels

Arterial Iron Content Is Increased in Patients with High Plasma Ferritin Levels

Abdominal Aortic Aneurysms Growth Is Associated With High Concentrations of Plasma Proteins in the Intraluminal Thrombus and Diseased Arterial Tissue

Research proposal: inflammation and oxidative stress in coronary artery bypass surgery graft: comparison between diabetic and non-diabetic patients

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