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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) is a gaseous lipophilic free radical generated by three distinct isoforms of nitric oxide synthases (NOS), type 1 or neuronal (nNOS), type 2 or inducible (iNOS) and type 3 or endothelial NOS (eNOS). Expression of eNOS is altered in many types of cardiovascular disease, such as atherosclerosis, diabetes and hypertension. The ubiquitous chaperone heat shock protein 90 (hsp90) associates with NOS and is important for its proper folding and function. Current studies point toward a therapeutic potential by modulating hsp90-NOS association in various vascular diseases. Here we review the transcriptional regulation of endothelial NOS and factors affecting eNOS activity and function, as well as the important vascular pathologies associated with altered NOS function, focusing on the regulatory role of hsp90 and other factors in NO-associated pathogenesis of these diseases.
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PMID:Endothelial nitric oxide (NO) and its pathophysiologic regulation. 1869 95

Nitric oxide (NO) exerts a variety of biological actions under both physiological and pathological conditions. NO is synthesized by three distinct NO synthase (NOS) isoforms, including neuronal (nNOS), inducible (iNOS), and endothelial NOS (eNOS), all of which are expressed in the human cardiovascular system. The roles of endogenous NO in the cardiovascular system have been investigated in pharmacological studies with NOS inhibitors and in studies with mice that lack each NOS isoform. However, in the pharmacological studies, the specificity of the NOS inhibitors continues to be an issue of debate, while in each of the NOS isoform-deficient mice, a compensatory mechanism by other NOSs that are not genetically deleted is apparently involved. Thus, the authentic roles of endogenous NO are still poorly understood. To address this issue, genetically engineered mice in which all three NOS genes are completely disrupted have been developed. In the triply n/i/eNOS(-/-) mice, but not in singly eNOS(-/-) mice, several cardiovascular phenotypes, including arteriosclerosis/atherosclerosis, myocardial infarction, and dyslipidemia, have been described. Furthermore, by using the triply NOS(-/-) mice, the roles of the NOS system in endothelium-dependent hyperpolarization and stain-induced NO production have been elucidated. These results provide novel insight into the cardiovascular role of the endogenous NO/NOS system at the molecular level. This review, based on the research outcomes obtained from the triply NOS(-/-) genetic model, summarizes the latest knowledge of the pathophysiological relevance of NO signaling in the cardiovascular system.
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PMID:Pathophysiological relevance of NO signaling in the cardiovascular system: novel insight from mice lacking all NO synthases. 2082 80

Caloric restriction is an established intervention, of which anti-aging effects are scientifically proven. It has pleiotropic effects on the cardiovascular system: vascular protection, improvement of myocardial ischemic tolerance and retardation of cardiac senescence. First, increasing evidence from both experimental and clinical studies supports the concept that "a man is as old as his arteries". Caloric restriction could prevent the progression of atherosclerosis and vascular aging through direct and indirect mechanisms. Second, the hearts of senescent animals are more susceptible to ischemia than those of young animals. We demonstrated that short-term and prolonged caloric restriction confers cardioprotection against ischemia/reperfusion injury in young and aged rodents. Furthermore, we showed that the increase in circulating adiponectin levels and subsequent activation of adenosine monophosphate-activated protein kinase are necessary for the cardioprotection afforded by short-term caloric restriction. In contrast, the mechanisms by which prolonged caloric restriction confers cardioprotection seem more complicated. Adiponectin, nitric oxide synthase and sirtuin may form a network of cardiovascular protection during caloric restriction. Recently, by using genetically engineered mice, we found that, in addition to endothelial nitric oxide synthase, neuronal nitric oxide synthase plays an essential role in the development of cardioprotection afforded by prolonged caloric restriction. Third, long-term caloric restriction has cardiac-specific effects that attenuate the age-associated impairment seen in left ventricular diastolic function. It is possible that long-term caloric restriction partially retards cardiac senescence by attenuating oxidative damage in the aged heart. Overall, we strongly believe that caloric restriction could reduce morbidity and mortality of cardiovascular events in humans.
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PMID:Cardiovascular protection afforded by caloric restriction: essential role of nitric oxide synthase. 2119 36

Nitric oxide (NO) formed via endothelial NO synthase (eNOS) plays crucial roles in the regulation of coronary blood flow through vasodilatation and decreased vascular resistance and in the inhibition of platelet aggregation and adhesion, leading to the prevention of coronary circulatory failure, thrombosis, and atherosclerosis. NO restrains myocardial oxygen consumption, when coronary perfusion is restricted. Endothelial function is impaired by pathogenic factors including smoking, excess salt intake, obesity, aging, hypercholesterolemia, hyperglycemia, and hypertension. The mechanisms involved in endothelial dysfunction are reduced NOS expression and activity, decreased NO bioavailability, and increased production of oxygen radicals and endogenous NOS inhibitors. NADPH oxidase, xanthine oxidase, and NOS uncoupling are involved in increased superoxide generation. Plasma levels of asymmetric dimethylarginine, the endogenous NOS inhibitor, are increased by an impairment of enzymatic degradation by dimethylarginine dimethylaminohydrolase and alanine-glyoxylate aminotransferase 2. Impairment of coronary arteriolar dilatation induced by perivascular nitrergic nerve activation is involved in decreased coronary blood flow. NO derived from nNOS singly or in combination with eNOS protects against serious myocardial injury through ischemic insults. Ischemia-induced iNOS upregulation contributes to myocardial contractile dysfunction. Preventive and therapeutic measures, such as improvement of life-style and treatment with therapeutic agents, to eliminate pathogenic factors for endothelial dysfunction or nNOS-derived NO deprivation would be quite important for the prophylaxis and minimizing the development of coronary artery disease.
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PMID:Coronary hemodynamic regulation by nitric oxide in experimental animals: recent advances. 2174 64

Periodontal disease is a highly prevalent chronic inflammatory disease and is associated with complex microbial infection in the subgingival cavity. Recently, American Heart Association supported a century old association between periodontal disease and atherosclerotic vascular disease. We have recently shown that polybacterial periodontal infection led to aortic atherosclerosis and modulation of lipid profiles; however the underlying mechanism(s) has not been yet demonstrated. Altered nitric oxide (NO) synthesis and tetrahydrobiopterin (BH4), a cofactor for nitric oxide synthases (NOS) has long been shown to be associated with vascular dysfunction and gastrointestinal motility disorders. We sought to examine the mechanism of periodontal infection leading to altered vascular and gastrointestinal smooth muscle relaxation, focusing on the BH4/nNOS pathways. In addition, we also have investigated how the antioxidant system (NRF2-Phase II enzyme expression) in vascular and GI specimens is altered by oral infection. Eight week old male ApoEnull mice were either sham-infected or infected orally for 16 weeks with a mixture of major periodontal bacteria Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia to induce experimental periodontitis. Serum, vascular (mesenteric), stomach, and colon specimens were collected at the end of periodontal pathogen infection. Bacterial infection induced significant (p<0.05) reductions in the levels of BH4,in ratio of BH4:BH2+B and also in nitric oxide levels compared to sham-infected controls. In addition, we identified a significant (p<0.05) reduction in eNOS dimerization, nNOS dimerization and protein expression of BH4 biosynthesis enzymes; GCH-1, DHFR and NRF2 & Phase II enzymes in infected mice versus controls in both mesenteric artery and colon tissues. However, we found no differences in nNOS/BH4 protein expression in stomach tissues of infected and sham-infected mice. This suggests that a polybacterial infection can cause significant changes in the vascular and colonic BH4/nNOS/NRF2 pathways which might lead to impaired vascular relaxation and colonic motility.
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PMID:Polybacterial Periodontal Pathogens Alter Vascular and Gut BH4/nNOS/NRF2-Phase II Enzyme Expression. 2611 Nov 53

Nitric oxide (NO) is synthesized by a family of NO synthases (NOS), including neuronal, inducible, and endothelial NOS (n/i/eNOS). NO-mediated effects can be beneficial or harmful depending on the specific risk factors affecting the disease. In hypertension, the vascular relaxation response to acetylcholine is blunted, and that to direct NO donors is maintained. A reduction in the activity of eNOS is mainly responsible for the elevation of blood pressure, and an abnormal expression of iNOS is likely to be related to the progression of vascular dysfunction. While eNOS/nNOS-derived NO is protective against the development of atherosclerosis, iNOS-derived NO may be proatherogenic. eNOS-derived NO may prevent the progression of myocardial infarction. Myocardial ischemia/reperfusion injury is significantly enhanced in eNOS-deficient animals. An important component of heart failure is the loss of coronary vascular eNOS activity. A pressure-overload may cause severer left ventricular hypertrophy and dysfunction in eNOS null mice than in wild-type mice. iNOS-derived NO has detrimental effects on the myocardium. NO plays an important role in regulating the angiogenesis and slowing the interstitial fibrosis of the obstructed kidney. In unilateral ureteral obstruction, the expression of eNOS was decreased in the affected kidney. In triply n/i/eNOS null mice, nephrogenic diabetes insipidus developed along with reduced aquaporin-2 abundance. In chronic kidney disease model of subtotal-nephrectomized rats, treatment with NOS inhibitors decreased systemic NO production and induced left ventricular systolic dysfunction (renocardiac syndrome).
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PMID:Altered Nitric Oxide System in Cardiovascular and Renal Diseases. 2723 71

The family of nitric oxide synthases (NOS) has significant importance in various physiological mechanisms and is also involved in many pathological processes. Three NOS isoforms have been identified: neuronal NOS (nNOS or NOS 1), endothelial NOS (eNOS or NOS 3), and an inducible NOS (iNOS or NOS 2). Both nNOS and eNOS are constitutively expressed. Classically, eNOS is considered the main isoform involved in the control of the vascular function. However, more recent studies have shown that nNOS is present in the vascular endothelium and importantly contributes to the maintenance of the homeostasis of the cardiovascular system. In physiological conditions, besides nitric oxide (NO), nNOS also produces hydrogen peroxide (H2O2) and superoxide ([Formula: see text]) considered as key mediators in non-neuronal cells signaling. This mini-review highlights recent scientific releases on the role of nNOS in vascular homeostasis and cardiovascular disorders such as hypertension and atherosclerosis.
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PMID:Neuronal Nitric Oxide Synthase in Vascular Physiology and Diseases. 2731 45

Cardiovascular disease (CVD) is the major cause of morbidity and mortality worldwide. The implication of estrogen in this disease has been extensively studied. While the vast majority of published research argue for a cardioprotective role of estrogen in vascular inflammation such as in atherosclerosis, the role of estrogen in hypertension remains far from being resolved. The vasorelaxant effect of estrogen has already been well-established. However, emerging evidence supports a vasoconstrictive potential of this hormone. It has been proposed that the microenvironment dictates the effect of estrogen-induced type 1 nitric oxide synthase-1 (nNOS) on vasotone. Indeed, depending on nNOS product, nitric oxide or superoxide, estrogen can induce vasodilation or vasoconstriction, respectively. In this review, we discuss the evidence supporting the vasorelaxant effects of estrogen, and the molecular players involved. Furthermore, we shed light on recent reports revealing a vasoconstrictive role of estrogen, and speculate on the underlying signaling pathways. In addition, we identify certain factors that can account for the discrepant estrogenic effects. This review emphasizes a yin-yang role of estrogen in regulating blood pressure.
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PMID:The hypertensive potential of estrogen: An untold story. 3162 18


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