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Disturbed Lipid Metabolism in Diabetic Patients with Manifest Coronary Artery Disease Is Associated with Enhanced Inflammation

Background: Diabetic vasculopathy plays an important role in the pathophysiology of coronary artery disease (CAD) with oxidative stress as a strong mediator. This study aims to elucidate the underlying pathomechanisms of diabetic cardiac vasculopathy leading to coronary disease with an emphasis on t...

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Autores principales: Buschmann, Katja, Gramlich, Yves, Chaban, Ryan, Oelze, Matthias, Hink, Ulrich, Münzel, Thomas, Treede, Hendrik, Daiber, Andreas, Duerr, Georg Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535387/
https://www.ncbi.nlm.nih.gov/pubmed/34682638
http://dx.doi.org/10.3390/ijerph182010892
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author Buschmann, Katja
Gramlich, Yves
Chaban, Ryan
Oelze, Matthias
Hink, Ulrich
Münzel, Thomas
Treede, Hendrik
Daiber, Andreas
Duerr, Georg Daniel
author_facet Buschmann, Katja
Gramlich, Yves
Chaban, Ryan
Oelze, Matthias
Hink, Ulrich
Münzel, Thomas
Treede, Hendrik
Daiber, Andreas
Duerr, Georg Daniel
author_sort Buschmann, Katja
collection PubMed
description Background: Diabetic vasculopathy plays an important role in the pathophysiology of coronary artery disease (CAD) with oxidative stress as a strong mediator. This study aims to elucidate the underlying pathomechanisms of diabetic cardiac vasculopathy leading to coronary disease with an emphasis on the role of oxidative stress. Therefore, novel insights into antioxidant pathways might contribute to new strategies in the treatment and prevention of diabetic CAD. Methods: In 20 patients with insulin-dependent or non-insulin dependent diabetes mellitus (IDDM/NIDDM) and 39 non-diabetic (CTR) patients, myocardial markers of oxidative stress, vasoactive proteins, endothelial nitric oxide synthase (eNOS), activated phosphorylated eNOS (p-eNOS), and antioxidant enzymes, e.g., tetrahydrobiopterin generating dihydrofolate reductase (DHFR), heme oxygenase (HO-1), as well as serum markers of inflammation, e.g., E-selectin, interleukin-6 (IL-6), and lipid metabolism, e.g., high- and low-density lipoptrotein (HDL- and LDL-cholesterol) were determined in specimens of right atrial tissue and in blood samples from type 2 diabetic and non-diabetic patients undergoing coronary artery bypass graft (CABG) surgery. Results: IDDM/NIDDM increased markers of inflammation (e.g., E-selectin, p = 0.005 and IL-6, p = 0.051), decreased the phosphorylated myocardial p-eNOS (p = 0.032), upregulated the myocardial stress response protein HO-1 (p = 0.018), and enhanced the serum LDL-/HDL-cholesterol ratio (p = 0.019). However, the oxidative stress markers in the myocardium and the expression of vasoactive proteins (eNOS, DHFR) showed only marginal adverse changes in patients with IDDM/NIDDM. Conclusion: Dyslipidemia and myocardial inflammation seem to be the major determinants of diabetic CAD complications. Dysregulation in pro-oxidative enzymes might be attributable to the severity of CAD and oxidative stress levels in all included patients undergoing CABG.
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spelling pubmed-85353872021-10-23 Disturbed Lipid Metabolism in Diabetic Patients with Manifest Coronary Artery Disease Is Associated with Enhanced Inflammation Buschmann, Katja Gramlich, Yves Chaban, Ryan Oelze, Matthias Hink, Ulrich Münzel, Thomas Treede, Hendrik Daiber, Andreas Duerr, Georg Daniel Int J Environ Res Public Health Article Background: Diabetic vasculopathy plays an important role in the pathophysiology of coronary artery disease (CAD) with oxidative stress as a strong mediator. This study aims to elucidate the underlying pathomechanisms of diabetic cardiac vasculopathy leading to coronary disease with an emphasis on the role of oxidative stress. Therefore, novel insights into antioxidant pathways might contribute to new strategies in the treatment and prevention of diabetic CAD. Methods: In 20 patients with insulin-dependent or non-insulin dependent diabetes mellitus (IDDM/NIDDM) and 39 non-diabetic (CTR) patients, myocardial markers of oxidative stress, vasoactive proteins, endothelial nitric oxide synthase (eNOS), activated phosphorylated eNOS (p-eNOS), and antioxidant enzymes, e.g., tetrahydrobiopterin generating dihydrofolate reductase (DHFR), heme oxygenase (HO-1), as well as serum markers of inflammation, e.g., E-selectin, interleukin-6 (IL-6), and lipid metabolism, e.g., high- and low-density lipoptrotein (HDL- and LDL-cholesterol) were determined in specimens of right atrial tissue and in blood samples from type 2 diabetic and non-diabetic patients undergoing coronary artery bypass graft (CABG) surgery. Results: IDDM/NIDDM increased markers of inflammation (e.g., E-selectin, p = 0.005 and IL-6, p = 0.051), decreased the phosphorylated myocardial p-eNOS (p = 0.032), upregulated the myocardial stress response protein HO-1 (p = 0.018), and enhanced the serum LDL-/HDL-cholesterol ratio (p = 0.019). However, the oxidative stress markers in the myocardium and the expression of vasoactive proteins (eNOS, DHFR) showed only marginal adverse changes in patients with IDDM/NIDDM. Conclusion: Dyslipidemia and myocardial inflammation seem to be the major determinants of diabetic CAD complications. Dysregulation in pro-oxidative enzymes might be attributable to the severity of CAD and oxidative stress levels in all included patients undergoing CABG. MDPI 2021-10-17 /pmc/articles/PMC8535387/ /pubmed/34682638 http://dx.doi.org/10.3390/ijerph182010892 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Buschmann, Katja
Gramlich, Yves
Chaban, Ryan
Oelze, Matthias
Hink, Ulrich
Münzel, Thomas
Treede, Hendrik
Daiber, Andreas
Duerr, Georg Daniel
Disturbed Lipid Metabolism in Diabetic Patients with Manifest Coronary Artery Disease Is Associated with Enhanced Inflammation
title Disturbed Lipid Metabolism in Diabetic Patients with Manifest Coronary Artery Disease Is Associated with Enhanced Inflammation
title_full Disturbed Lipid Metabolism in Diabetic Patients with Manifest Coronary Artery Disease Is Associated with Enhanced Inflammation
title_fullStr Disturbed Lipid Metabolism in Diabetic Patients with Manifest Coronary Artery Disease Is Associated with Enhanced Inflammation
title_full_unstemmed Disturbed Lipid Metabolism in Diabetic Patients with Manifest Coronary Artery Disease Is Associated with Enhanced Inflammation
title_short Disturbed Lipid Metabolism in Diabetic Patients with Manifest Coronary Artery Disease Is Associated with Enhanced Inflammation
title_sort disturbed lipid metabolism in diabetic patients with manifest coronary artery disease is associated with enhanced inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535387/
https://www.ncbi.nlm.nih.gov/pubmed/34682638
http://dx.doi.org/10.3390/ijerph182010892
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