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

Abstract

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.

Detrimental Effects of Lipid Peroxidation in Type 2 Diabetes: Exploring the Neutralizing Influence of Antioxidants

“…In addition, Miwa et al (2000) suggested that the excessive production of 4-HNE impairs glucose-stimulated insulin secretion in isolated pancreatic β-cells, contributing to the death of pancreatic β-cells in T2D [ 78 ]. It is noteworthy that patients with T2D are at increased risk of developing metabolic complications and cardiovascular disease (CVD), especially through the formation of diverse microvascular and macrovascular abnormalities, leading to increased morbidity and mortality [ 80 , 81 , 82 ]. Apparently, T2D is responsible for at least two-four-fold rise in the incidence of coronary artery disease, which is linked with accelerated heart failure in patients with diabetes [ 81 , 82 ].…”

“…It is noteworthy that patients with T2D are at increased risk of developing metabolic complications and cardiovascular disease (CVD), especially through the formation of diverse microvascular and macrovascular abnormalities, leading to increased morbidity and mortality [ 80 , 81 , 82 ]. Apparently, T2D is responsible for at least two-four-fold rise in the incidence of coronary artery disease, which is linked with accelerated heart failure in patients with diabetes [ 81 , 82 ]. Furthermore, biomarkers of cardiometabolic diseases, such as low-density lipoprotein and total cholesterol, in relation with oxidative stress, are much higher in these patients when compared to non-diabetic controls [ 71 , 81 ].…”

“…Apparently, T2D is responsible for at least two-four-fold rise in the incidence of coronary artery disease, which is linked with accelerated heart failure in patients with diabetes [ 81 , 82 ]. Furthermore, biomarkers of cardiometabolic diseases, such as low-density lipoprotein and total cholesterol, in relation with oxidative stress, are much higher in these patients when compared to non-diabetic controls [ 71 , 81 ]. Figure 2 gives a general perspective to highlight some of the pathological consequences of oxidative stress in conditions of hyperglycemia; of which lipid peroxidation is a major component that correlated positively with protein as well as nucleic acid oxidation which is indicated by increased advanced glycation end products (AGEs) and 8-hydroxydeoxyguanosine (8-OHDG), respectively [ 83 , 84 ].…”

“…Some prominent antioxidants, such as CAT, CoQ 10 , GSH, SOD, and some vitamins (such as C and E), are compromised with the elevation of lipid peroxidation, which usually links with the severity of T2D. On the other hand, increasing research considers antioxidant therapies are considered essential for the alleviation of oxidative stress and better management of T2D [ 81 , 148 , 149 , 150 ]. Supplementation with foods rich in antioxidants such as fruits, vegetables, and tea has been linked with lower oxidative stress and enhanced intracellular antioxidants in T2D or related metabolic complications [ 110 , 151 , 152 , 153 ].…”

Effect of Oral Chinese Herbal Preparations Regulating Intestinal Flora on Lipid Metabolism Disorders in Patients: A Meta-Analysis of Controlled Clinical Studies

“…Lipid metabolism disorders, also known as dyslipidemia, refer to the abnormal increase of one or more of the indicators of triacylglycerol, total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) in human serum ( 1 ). With the gradual improvement of people's living standards and changes in dietary structure in China, dyslipidemia has become one of the major diseases threatening the health of middle-aged and elderly people, and is the main cause of atherosclerosis (AS) and coronary heart disease (CHD), damaging the health of patients ( 2 ). Lipid metabolism disorders often emerge with diseases such as obesity, diabetes, and ovarian syndrome, causing complex effects on the human body ( 3 ).…”