Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelins are endothelial peptides, the properties of which have been investigated for over 25 years. They play a special role in the pathophysiology of many diseases of the cardiovascular system. Endothelin-1, which is the most explored one, is a potent vasoconstrictor. It increases renal water and sodium excretion, augments cell growth and proliferation and has proinflammatory activity, by intensifying the production of reactive oxygen and nitrogen species (ROS and RNS). ET-1 takes part in the progression of such diseases as hypertension, atherosclerosis, heart and renal failure. The physio- and pathological effects of endothelins are mediated through ETA and ETB receptors. Blocking these receptors, in particular the ETA receptor, can prevent negative effects of endothelins. Long-term efforts to create drugs which act like that have brought relevant results. Endothelin receptor antagonists (ERA) are a new class of medicines, which are indicated in the treatment of pulmonary arterial hypertension. There are also optimistic results of trials with ERA administered in other disorders. On the basis of these data we may conclude that there will be more indications for this group of drugs. This review discusses properties and new research directions of ERA registered in pharmacotherapy.
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PMID:[Endothelin receptor antagonists--a brief description of the new class of drugs]. 2522 16

Despite the wealth of pre-clinical support for a role for reactive oxygen and nitrogen species (ROS/RNS) in the aetiology of diabetic complications, enthusiasm for antioxidant therapeutic approaches has been dampened by less favourable outcomes in large clinical trials. This has necessitated a re-evaluation of pre-clinical evidence and a more rational approach to antioxidant therapy. The present review considers current evidence, from both pre-clinical and clinical studies, to address the benefits of antioxidant therapy. The main focus of the present review is on the effects of direct targeting of ROS-producing enzymes, the bolstering of antioxidant defences and mechanisms to improve nitric oxide availability. Current evidence suggests that a more nuanced approach to antioxidant therapy is more likely to yield positive reductions in end-organ injury, with considerations required for the types of ROS/RNS involved, the timing and dosage of antioxidant therapy, and the selective targeting of cell populations. This is likely to influence future strategies to lessen the burden of diabetic complications such as diabetes-associated atherosclerosis, diabetic nephropathy and diabetic retinopathy.
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PMID:Are reactive oxygen species still the basis for diabetic complications? 2592 80

Reactive oxygen and nitrogen species (ROS and RNS, e.g. H2O2, nitric oxide) confer redox regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. At higher concentrations, ROS and RNS lead to oxidative stress and oxidative damage of biomolecules (e.g. via formation of peroxynitrite, fenton chemistry). Peripheral artery disease (PAD) is characterized by severe ischemic conditions in the periphery leading to intermittent claudication and critical limb ischemia (end stage). It is well known that redox biology and oxidative stress play an important role in this setting. We here discuss the major pathways of oxidative stress and redox signaling underlying the disease progression with special emphasis on the contribution of inflammatory processes. We also highlight therapeutic strategies comprising pharmacological (e.g. statins, angiotensin-converting enzyme inhibitors, phosphodiesterase inhibition) and non-pharmacological (e.g. exercise) interventions. Both of these strategies induce potent indirect antioxidant and anti-inflammatory mechanisms that may contribute to an improvement of PAD associated complications and disease progression by removing excess formation of ROS and RNS (e.g. by ameliorating primary complications such as hyperlipidemia and hypertension) as well as the normalization of the inflammatory phenotype suppressing the progression of atherosclerosis.
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PMID:Peripheral artery disease, redox signaling, oxidative stress - Basic and clinical aspects. 2843 55

Atherogenesis, the formation of atherosclerotic plaques, is a complex process that involves several mechanisms, including endothelial dysfunction, neovascularization, vascular proliferation, apoptosis, matrix degradation, inflammation, and thrombosis. The pathogenesis and progression of atherosclerosis are explained differently by different scholars. One of the most common theories is the destruction of well-balanced homeostatic mechanisms, which incurs the oxidative stress. And oxidative stress is widely regarded as the redox status realized when an imbalance exists between antioxidant capability and activity species including reactive oxygen (ROS), nitrogen (RNS) and halogen species, non-radical as well as free radical species. This occurrence results in cell injury due to direct oxidation of cellular protein, lipid, and DNA or via cell death signaling pathways responsible for accelerating atherogenesis. This paper discusses inflammation, mitochondria, autophagy, apoptosis, and epigenetics as they induce oxidative stress in atherosclerosis, as well as various treatments for antioxidative stress that may prevent atherosclerosis.
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PMID:Oxidative Stress-Mediated Atherosclerosis: Mechanisms and Therapies. 2887 85

The incidence and prevalence of cardiovascular disease is highest among the elderly, in part, due to deleterious effects of advancing age on the heart and blood vessels. Aging, a known cardiovascular risk factor, is progressively associated with structural and functional changes to the vasculature including hemodynamic disturbance due to increased oxidative stress, premature cellular senescence and impairments in synthesis and/or secretion of endothelium-derived vasoactive molecules. These molecular and physiological changes lead to vessel wall stiffening and thickening, as well as other vascular complications that culminate to loss of vascular tone regulation and endothelial function. Intriguingly, the vessel wall, a biochemically active structure composed of collagen, connective tissue, smooth muscle and endothelial cells, is adversely affected by processes involved in premature or normal aging. Notably, the inner most layer of the vessel wall, the endothelium, becomes senescent and dysfunctional with advancing age. As a result, its ability to release vasoactive molecules such as acetylcholine (ACh), prostacyclin (PGI2), endothelium-derived hyperpolarizing factor (EDHF), and nitric oxide (NO) is reduced and the cellular response to these molecules is also impaired. By contrast, the vascular endothelium increases its generation and release of reactive oxygen (ROS) and nitrogen (RNS) species, vasoconstrictors such as endothelin (ET) and angiotensin (AT), and endogenous inhibitors of NO synthases (NOSs) to block NO. This skews the balance of the endothelium in favor of the release of highly tissue reactive and harmful molecules that promote DNA damage, telomere erosion, senescence, as well as stiffened and hardened vessel wall that is prone to the development of hypertension, diabetes, atherosclerosis and other cardiovascular risk factors. This Review discusses the impact of advancing age on cardiovascular health, and highlights the cellular and molecular mechanisms that underlie age-associated vascular changes. In addition, the role of pharmacological interventions in preventing or delaying age-related cardiovascular disease is discussed.
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PMID:Vascular Aging: Implications for Cardiovascular Disease and Therapy. 2893 25

Oxidative stress (OS), defined as disturbances in the pro-/antioxidant balance, is harmful to cells due to the excessive generation of highly reactive oxygen (ROS) and nitrogen (RNS) species. When the balance is not disturbed, OS has a role in physiological adaptations and signal transduction. However, an excessive amount of ROS and RNS results in the oxidation of biological molecules such as lipids, proteins, and DNA. Oxidative stress has been reported in kidney disease, due to both antioxidant depletions as well as increased ROS production. The kidney is a highly metabolic organ, rich in oxidation reactions in mitochondria, which makes it vulnerable to damage caused by OS, and several studies have shown that OS can accelerate kidney disease progression. Also, in patients at advanced stages of chronic kidney disease (CKD), increased OS is associated with complications such as hypertension, atherosclerosis, inflammation, and anemia. In this review, we aim to describe OS and its influence on CKD progression and its complications. We also discuss the potential role of various antioxidants and pharmacological agents, which may represent potential therapeutic targets to reduce OS in both pediatric and adult CKD patients.
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PMID:Oxidative stress in chronic kidney disease. 3010 14

Ionizing radiation (IR) leads to a variety of the cardiovascular diseases, including the arterial hypertension. A number of studies have demonstrated that blood vessels represent important target for IR, and the endothelium is one of the most vulnerable components of the vascular wall. IR causes an inhibition of nitric oxide (NO)-mediated endothelium-dependent vasodilatation and generation of reactive oxygen (ROS) and nitrogen (RNS) species trigger this process. Inhibition of NO-mediated vasodilatation could be due to endothelial NO synthase (eNOS) down-regulation, inactivation of endothelium-derived NO, and abnormalities in diffusion of NO from the endothelial cells (ECs) leading to a decrease in NO bioavailability. Beside this, IR suppresses endothelial large conductance Ca2+-activated K+ channels (BKCa) activity, which control NO synthesis. IR also leads to inhibition of the BKCa current in vascular smooth muscle cells (SMCs) which is mediated by protein kinase C (PKC). On the other hand, IR-evoked enhanced vascular contractility may result from PKC-mediated increase in SMCs myofilament Ca2+ sensitivity. Also, IR evokes vascular wall inflammation and atherosclerosis development. Vascular function damaged by IR can be effectively restored by quercetin-filled phosphatidylcholine liposomes and mesenchymal stem cells injection. Using RNA-interference technique targeted to different PKC isoforms can also be a perspective approach for pharmacological treatment of IR-induced vascular dysfunction.
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PMID:Mechanisms of vascular dysfunction evoked by ionizing radiation and possible targets for its pharmacological correction. 3050 25


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