Hyperglycemia and Oxidative Stress Strengthen the Association Between Myeloperoxidase and Blood Pressure

Abstract

Abstract-Scavenging of the vasodilator nitric oxide by myeloperoxidase activity in the vasculature may contribute to hypertension. Because hydrogen peroxide is a cosubstrate of myeloperoxidase, hyperglycemia-induced oxidative stress may strengthen the relationship between myeloperoxidase and blood pressure. We investigated this relationship and its modification by hyperglycemia and oxidative stress in a population-based cohort of elderly subjects with normal glucose metabolism (nϭ267), impaired glucose metabolism (nϭ189), and type 2 diabetes (nϭ290 Many studies have demonstrated that systemic MPO levels predict risk throughout the spectrum of cardiovascular diseases. 4 -8 MPO catalyzes the production of hypochlorous acid and a range of other highly reactive species. These MPOderived reactive substances may damage the arterial wall, thereby reducing its elasticity. In addition, by several mechanisms, MPO reduces the bioavailability of the endogenous vasodilator nitric oxide. 3,9 Together, these mechanisms may lead to an increase in blood pressure. Because hydrogen peroxide is an obligate cosubstrate of MPO, the activity of MPO in the vasculature may be enhanced by increased local production of reactive oxygen species. Vascular production of superoxide and its dismutation product hydrogen peroxide has been shown to be stimulated by high glucose concentrations, resulting in increased activity of MPO. 10 We therefore hypothesize that the relationship between MPO and blood pressure is stronger on a background of (hyperglycemiainduced) oxidative stress.The aims of our study were to assess the relationship between plasma levels of MPO and blood pressure and to test the hypothesis that this relationship is strengthened by (hyperglycemia-induced) oxidative stress. Methods SubjectsThe present study was conducted in the Hoorn Study 11 follow-up examination conducted in 2000 and the Hoorn Screening Study, 12 both of which are population-based studies in a white population. From the 822 participants, we excluded subjects with missing data on primary variables of interest, leaving 746 subjects, of whom 267

A new fructose-free, resistant-starch type IV-enriched enteral formula improves glycaemic control and cardiovascular risk biomarkers when administered for six weeks to elderly diabetic patients

“…In this sense, feeding the DSF during 6 weeks did not alter plasma oxLDL, indicating that oxidative stress is not increased during the intervention. Myeloperoxidase is an enzyme linked to both oxidative stress and inflammation, and may promote atherogenesis (22). Patients with type 2 diabetes have shown elevated levels of these molecules compared with non-diabetic population (23), and increasing myeloperoxidase levels were associated with greater progression of atherosclerosis in diabetic patients (24).…”

Reactive oxygen species and vascular biology: implications in human hypertension

“…149,150 Plasma levels of asymmetric dimethylarginine (endothelial nitric oxide synthase inhibitor) and the lipid peroxidation product of linoleic acid, 13-hydroxyoctadecadienoic acid, a marker of ROS production, were inversely correlated with microvascular endothelial dysfunction and elevated blood pressure in hypertensive patients. To further support a relationship between oxidative stress and blood pressure, Van et al 151 recently showed that myeloperoxidase is positively and independently associated with blood pressure and that this association is strongest in subjects with increased levels of oxidative markers. Phagocytic NADPH oxidase activity is increased in obese subjects, possibly due to hyperleptinemia, and is related to vascular remodeling and preclinical atherosclerosis, risk factors associated with hypertension.…”

Association of Interleukin-6 and Myeloperoxidase with Insulin Resistance in Impaired Fasting Glucose Subjects

“…fasting. A positive correlation of MPO with FPG (Table 3) in IFG group indicates the role of high glucose concentrations in stimulating vascular production of MPO and its reactive oxygen species causing deleterious effects [23].…”