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

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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. / Preil, Simone A R; Kristensen, Lars P; Beck, Hans C; Jensen, Pia S; Nielsen, Patricia S; Steiniche, Torben; Bjørling-Poulsen, Marina; Larsen, Martin R; Hansen, Maria L; Rasmussen, Lars M.

In: Circulation: Cardiovascular Genetics, Vol. 8, No. 5, 10.2015, p. 727-35.

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Preil, Simone A R ; Kristensen, Lars P ; Beck, Hans C ; Jensen, Pia S ; Nielsen, Patricia S ; Steiniche, Torben ; Bjørling-Poulsen, Marina ; Larsen, Martin R ; Hansen, Maria L ; Rasmussen, Lars M. / 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. In: Circulation: Cardiovascular Genetics. 2015 ; Vol. 8, No. 5. pp. 727-35.

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@article{bf046890d13a44db98b3ee7d5cdc5e6f,
title = "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",
abstract = "BACKGROUND: The increased risk of cardiovascular diseases in type 2 diabetes mellitus has been extensively documented, but the origins of the association remain largely unknown. We sought to determine changes in protein expressions in arterial tissue from patients with type 2 diabetes mellitus and moreover hypothesized that metformin intake influences the protein composition.METHODS AND RESULTS: We analyzed nonatherosclerotic repair arteries gathered at coronary bypass operations from 30 patients with type 2 diabetes mellitus and from 30 age- and sex-matched nondiabetic individuals. Quantitative proteome analysis was performed by isobaric tag for relative and absolute quantitation-labeling and liquid chromatography-mass spectrometry, tandem mass spectrometry analysis on individual arterial samples. The amounts of the basement membrane components, α1-type IV collagen and α2-type IV collagen, γ1-laminin and β2-laminin, were significantly increased in patients with diabetes mellitus. Moreover, the expressions of basement membrane components and other vascular proteins were significantly lower among metformin users when compared with nonusers. Patients treated with or without metformin had similar levels of hemoglobin A1c, cholesterol, and blood pressure. In addition, quantitative histomorphometry showed increased area fractions of collagen-stainable material in tunica intima and media among patients with diabetes mellitus.CONCLUSIONS: The distinct accumulation of arterial basement membrane proteins in type 2 diabetes mellitus discloses a similarity between the diabetic macroangiopathy and microangiopathy and suggests a molecular explanation behind the alterations in vascular remodeling, biomechanical properties, and aneurysm formation described in diabetes mellitus. The lower amounts of basement membrane components in metformin-treated individuals are compatible with the hypothesis of direct beneficial drug effects on the matrix composition in the vasculature.",
keywords = "Aged, Basement Membrane, Diabetes Mellitus, Type 2, Female, Humans, Hypoglycemic Agents, Male, Mammary Arteries, Membrane Proteins, Metformin, Proteome, Journal Article, Research Support, Non-U.S. Gov't",
author = "Preil, {Simone A R} and Kristensen, {Lars P} and Beck, {Hans C} and Jensen, {Pia S} and Nielsen, {Patricia S} and Torben Steiniche and Marina Bj{\o}rling-Poulsen and Larsen, {Martin R} and Hansen, {Maria L} and Rasmussen, {Lars M}",
note = "{\circledC} 2015 American Heart Association, Inc.",
year = "2015",
month = "10",
doi = "10.1161/CIRCGENETICS.115.001165",
language = "English",
volume = "8",
pages = "727--35",
journal = "Circulation: Cardiovascular Genetics",
issn = "1942-325X",
publisher = "Lippincott Williams & Wilkins",
number = "5",

}

RIS

TY - JOUR

T1 - 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

AU - Preil, Simone A R

AU - Kristensen, Lars P

AU - Beck, Hans C

AU - Jensen, Pia S

AU - Nielsen, Patricia S

AU - Steiniche, Torben

AU - Bjørling-Poulsen, Marina

AU - Larsen, Martin R

AU - Hansen, Maria L

AU - Rasmussen, Lars M

N1 - © 2015 American Heart Association, Inc.

PY - 2015/10

Y1 - 2015/10

N2 - BACKGROUND: The increased risk of cardiovascular diseases in type 2 diabetes mellitus has been extensively documented, but the origins of the association remain largely unknown. We sought to determine changes in protein expressions in arterial tissue from patients with type 2 diabetes mellitus and moreover hypothesized that metformin intake influences the protein composition.METHODS AND RESULTS: We analyzed nonatherosclerotic repair arteries gathered at coronary bypass operations from 30 patients with type 2 diabetes mellitus and from 30 age- and sex-matched nondiabetic individuals. Quantitative proteome analysis was performed by isobaric tag for relative and absolute quantitation-labeling and liquid chromatography-mass spectrometry, tandem mass spectrometry analysis on individual arterial samples. The amounts of the basement membrane components, α1-type IV collagen and α2-type IV collagen, γ1-laminin and β2-laminin, were significantly increased in patients with diabetes mellitus. Moreover, the expressions of basement membrane components and other vascular proteins were significantly lower among metformin users when compared with nonusers. Patients treated with or without metformin had similar levels of hemoglobin A1c, cholesterol, and blood pressure. In addition, quantitative histomorphometry showed increased area fractions of collagen-stainable material in tunica intima and media among patients with diabetes mellitus.CONCLUSIONS: The distinct accumulation of arterial basement membrane proteins in type 2 diabetes mellitus discloses a similarity between the diabetic macroangiopathy and microangiopathy and suggests a molecular explanation behind the alterations in vascular remodeling, biomechanical properties, and aneurysm formation described in diabetes mellitus. The lower amounts of basement membrane components in metformin-treated individuals are compatible with the hypothesis of direct beneficial drug effects on the matrix composition in the vasculature.

AB - BACKGROUND: The increased risk of cardiovascular diseases in type 2 diabetes mellitus has been extensively documented, but the origins of the association remain largely unknown. We sought to determine changes in protein expressions in arterial tissue from patients with type 2 diabetes mellitus and moreover hypothesized that metformin intake influences the protein composition.METHODS AND RESULTS: We analyzed nonatherosclerotic repair arteries gathered at coronary bypass operations from 30 patients with type 2 diabetes mellitus and from 30 age- and sex-matched nondiabetic individuals. Quantitative proteome analysis was performed by isobaric tag for relative and absolute quantitation-labeling and liquid chromatography-mass spectrometry, tandem mass spectrometry analysis on individual arterial samples. The amounts of the basement membrane components, α1-type IV collagen and α2-type IV collagen, γ1-laminin and β2-laminin, were significantly increased in patients with diabetes mellitus. Moreover, the expressions of basement membrane components and other vascular proteins were significantly lower among metformin users when compared with nonusers. Patients treated with or without metformin had similar levels of hemoglobin A1c, cholesterol, and blood pressure. In addition, quantitative histomorphometry showed increased area fractions of collagen-stainable material in tunica intima and media among patients with diabetes mellitus.CONCLUSIONS: The distinct accumulation of arterial basement membrane proteins in type 2 diabetes mellitus discloses a similarity between the diabetic macroangiopathy and microangiopathy and suggests a molecular explanation behind the alterations in vascular remodeling, biomechanical properties, and aneurysm formation described in diabetes mellitus. The lower amounts of basement membrane components in metformin-treated individuals are compatible with the hypothesis of direct beneficial drug effects on the matrix composition in the vasculature.

KW - Aged

KW - Basement Membrane

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Humans

KW - Hypoglycemic Agents

KW - Male

KW - Mammary Arteries

KW - Membrane Proteins

KW - Metformin

KW - Proteome

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1161/CIRCGENETICS.115.001165

DO - 10.1161/CIRCGENETICS.115.001165

M3 - Journal article

C2 - 26371159

VL - 8

SP - 727

EP - 735

JO - Circulation: Cardiovascular Genetics

JF - Circulation: Cardiovascular Genetics

SN - 1942-325X

IS - 5

ER -