Quantitative Proteome Analysis Reveals Increased Content of Basement Membrane Proteins in Arteries from Patients with Type 2 Diabetes and Lower Levels among Metformin Users

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

BACKGROUND: -The increased risk of cardiovascular diseases (CVD) in type 2 diabetes 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 and moreover hypothesized that metformin intake influences the protein composition.

METHODS AND RESULTS: -We analyzed non-atherosclerotic repair arteries gathered at coronary by-pass operations from 30 patients with type 2 diabetes, as well as from 30 age- and gender-matched non-diabetic individuals. Quantitative proteome analysis was done by iTRAQ-labelling and LC-MS/MS analysis on individual arterial samples. The amounts of the basement membrane (BM) components, alpha-1- and alpha-2- type IV collagen, gamma-1- and beta-2-laminin were significantly increased in patients with diabetes. Moreover, the expressions of basement membrane components and other vascular proteins were significantly lower among metformin users, as compared to non-users. Patients treated with or without metformin had similar levels of HbA1c, 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.

CONCLUSIONS: -The distinct accumulation of arterial basement membrane proteins in type 2 diabetes discloses a similarity between the diabetic macro- and micro-angiopathy and suggests a molecular explanation behind the alterations in vascular remodeling, biomechanical properties, and aneurysm formation described in diabetes. 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.

OriginalsprogEngelsk
TidsskriftCirculation: Cardiovascular Genetics
Vol/bind8
Sider (fra-til)727-35
ISSN1942-325X
DOI
StatusUdgivet - 14. sep. 2015

Fingeraftryk

Proteome
Type 2 Diabetes Mellitus
Membrane Proteins
Proteins
Collagen Type II
Laminin
Pharmaceutical Preparations

Citer dette

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title = "Quantitative Proteome Analysis Reveals Increased Content of Basement Membrane Proteins in Arteries from Patients with Type 2 Diabetes and Lower Levels among Metformin Users",
abstract = "BACKGROUND: -The increased risk of cardiovascular diseases (CVD) in type 2 diabetes 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 and moreover hypothesized that metformin intake influences the protein composition.METHODS AND RESULTS: -We analyzed non-atherosclerotic repair arteries gathered at coronary by-pass operations from 30 patients with type 2 diabetes, as well as from 30 age- and gender-matched non-diabetic individuals. Quantitative proteome analysis was done by iTRAQ-labelling and LC-MS/MS analysis on individual arterial samples. The amounts of the basement membrane (BM) components, alpha-1- and alpha-2- type IV collagen, gamma-1- and beta-2-laminin were significantly increased in patients with diabetes. Moreover, the expressions of basement membrane components and other vascular proteins were significantly lower among metformin users, as compared to non-users. Patients treated with or without metformin had similar levels of HbA1c, 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.CONCLUSIONS: -The distinct accumulation of arterial basement membrane proteins in type 2 diabetes discloses a similarity between the diabetic macro- and micro-angiopathy and suggests a molecular explanation behind the alterations in vascular remodeling, biomechanical properties, and aneurysm formation described in diabetes. 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.",
author = "{R{\o}rdam Preil}, Simone 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}",
year = "2015",
month = "9",
day = "14",
doi = "10.1161/CIRCGENETICS.115.001165",
language = "English",
volume = "8",
pages = "727--35",
journal = "Circulation: Cardiovascular Genetics",
issn = "1942-325X",
publisher = "Lippincott Williams & Wilkins",

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Quantitative Proteome Analysis Reveals Increased Content of Basement Membrane Proteins in Arteries from Patients with Type 2 Diabetes and Lower Levels among Metformin Users. / Rørdam Preil, Simone; 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.

I: Circulation: Cardiovascular Genetics, Bind 8, 14.09.2015, s. 727-35.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Quantitative Proteome Analysis Reveals Increased Content of Basement Membrane Proteins in Arteries from Patients with Type 2 Diabetes and Lower Levels among Metformin Users

AU - Rørdam Preil, Simone

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

PY - 2015/9/14

Y1 - 2015/9/14

N2 - BACKGROUND: -The increased risk of cardiovascular diseases (CVD) in type 2 diabetes 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 and moreover hypothesized that metformin intake influences the protein composition.METHODS AND RESULTS: -We analyzed non-atherosclerotic repair arteries gathered at coronary by-pass operations from 30 patients with type 2 diabetes, as well as from 30 age- and gender-matched non-diabetic individuals. Quantitative proteome analysis was done by iTRAQ-labelling and LC-MS/MS analysis on individual arterial samples. The amounts of the basement membrane (BM) components, alpha-1- and alpha-2- type IV collagen, gamma-1- and beta-2-laminin were significantly increased in patients with diabetes. Moreover, the expressions of basement membrane components and other vascular proteins were significantly lower among metformin users, as compared to non-users. Patients treated with or without metformin had similar levels of HbA1c, 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.CONCLUSIONS: -The distinct accumulation of arterial basement membrane proteins in type 2 diabetes discloses a similarity between the diabetic macro- and micro-angiopathy and suggests a molecular explanation behind the alterations in vascular remodeling, biomechanical properties, and aneurysm formation described in diabetes. 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 (CVD) in type 2 diabetes 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 and moreover hypothesized that metformin intake influences the protein composition.METHODS AND RESULTS: -We analyzed non-atherosclerotic repair arteries gathered at coronary by-pass operations from 30 patients with type 2 diabetes, as well as from 30 age- and gender-matched non-diabetic individuals. Quantitative proteome analysis was done by iTRAQ-labelling and LC-MS/MS analysis on individual arterial samples. The amounts of the basement membrane (BM) components, alpha-1- and alpha-2- type IV collagen, gamma-1- and beta-2-laminin were significantly increased in patients with diabetes. Moreover, the expressions of basement membrane components and other vascular proteins were significantly lower among metformin users, as compared to non-users. Patients treated with or without metformin had similar levels of HbA1c, 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.CONCLUSIONS: -The distinct accumulation of arterial basement membrane proteins in type 2 diabetes discloses a similarity between the diabetic macro- and micro-angiopathy and suggests a molecular explanation behind the alterations in vascular remodeling, biomechanical properties, and aneurysm formation described in diabetes. 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.

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

ER -