Endothelial Function and Oxidative Stress in Cardiovascular Diseases

Abstract

Circ J 2009; 73: 411 -418 arious vasodilators, including nitric oxide (NO), prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF), as well as vasoconstrictors, are released from the endothelium. 1,2 NO plays an important role in the regulation of vascular tone, inhibition of platelet aggregation, and suppression of vascular smooth muscle cell proliferation. 3,4 Impaired endothelium-dependent vasodilation has been found in the forearm, coronary, and renal vasculature of patients with hypertension, 5-11 dyslipidemia, 12,13 diabetes mellitus, [14][15][16] and coronary artery diseases. [17][18][19][20][21] Endothelial dysfunction is an early feature of both atherosclerosis and vascular diseases in humans. 22 Improvement or augmentation of endothelial function will prevent the development of atherosclerosis, resulting in a reduction in cardiac events.There are several possible mechanisms for impaired endothelial function in patients with cardiovascular diseases. Decreased NO bioavailability (decreased NO production and/or increased NO inactivation) induces endothelial dysfunction. A balance of endothelium-derived vasodilators, especially NO, and reactive oxygen species (ROS) modulates endothelial function. Therefore, an imbalance of NO and ROS, so-called oxidative stress, is involved in endothelial dysfunction through the inactivation of NO. Oxidative Stress in Cardiovascular DiseasesROS are produced by various oxidase enzymes, including nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, xanthine oxidase, uncoupled endothelial NO synthase (eNOS), cyclooxygenase, glucose oxidase, and lipooxygenase, and mitochondrial electron transport (Figure 1). ROS include superoxide anion (O2 -), hydrogen peroxide (H2O2), hydroxyl radical (OH), hypochlorous acid (HOCl), NO, and peroxynitrite (ONOO -). O2 -, OH, and NO are classified as free radicals that have unpaired electrons and potent oxidation ability. H2O2, HOCl, and ONOO -are classified as non-free radicals that also have oxidation ability. The sources of ROS are a variety of cell types, including vascular smooth muscle cells (VSMCs), endothelial cells and mononuclear cells. The antioxidant enzyme superoxide dismutase (SOD) has been identified as 3 enzymatic types: Cu/Zn SOD, Mn SOD, and extracellular SOD. SOD rapidly dismutates O2 -to H2O2, then H2O2 is eliminated by glutathione peroxidase (GPx) and catalase to water.Several lines of evidence demonstrate that oxidative stress plays an important role in the pathogenesis and development of cardiovascular diseases, including hypertension, dyslipidemia, diabetes mellitus, atherosclerosis, myocardial infraction, angina pectoris, and heart failure. [23][24][25][26] The susceptibility of vascular cells to oxidative stress is a function of the overall balance between the degree of oxidative stress and the antioxidant defense capability. Protective antioxidant mechanisms are complex and multifactorial. Antioxidant defense systems, such as SOD, GPx and catalase, scavenge ROS in the vasculature, resulting i...

Endothelial Dysfunction, Increased Arterial Stiffness, and Cardiovascular Risk Prediction in Patients With Coronary Artery Disease: FMD‐J (Flow‐Mediated Dilation Japan) Study A

“…Impairment of vascular function, such as endothelial dysfunction and increased arterial stiffness, is closely associated with the development and maintenance of atherosclerotic conditions, leading to target organ damage and cardiovascular complications 10. Therefore, vascular function tests could be used not only as markers of atherosclerosis but also as prognostic markers of cardiovascular events 11.…”

Endothelial Function Assessed by Automatic Measurement of Enclosed Zone Flow‐Mediated Vasodilation Using an Oscillometric Method Is an Independent Predictor of Cardiovascular Events

“…Endothelial dysfunction is the earliest event in atherosclerosis, leading to cardiovascular complications 1, 2. Several investigators, including us, have reported that endothelial function evaluated by FMD can serve as an independent predictor of cardiovascular events 10, 11, 12, 13, 14.…”

“…Aging, smoking, obesity, hypertension, dyslipidemia, and diabetes mellitus are well‐known risk factors of endothelial dysfunction 1, 2, 3, 4, 7, 8, 9, 23, 24, 25. We previously showed that ezFMD was significantly correlated with cardiovascular risk factors and endothelial function assessed by FMD in relatively young participants 15.…”

“…Second, we measured ezFMD just 1 time, when the participants were enrolled. It is well known that endothelial function can be modified by interventions including aerobic exercise, body weight reduction, and pharmacological therapy 2. Several investigators have shown that repeated assessment of vascular function has much greater predictive power of cardiovascular disease progression and cardiovascular outcomes 26, 27.…”

“…Endothelial dysfunction is the initial event in atherosclerosis and plays a key role in atherogenesis, resulting in cardiovascular complications 1, 2. It is clinically important to assess endothelial function for early detection of atherosclerosis.…”