Stimulatory Effects of Atorvastatin on Extracellular Nucleotide Degradation in Human Endothelial Cells

Osman, Lana; Amrani, Mohamed; Isley, C.; Yacoub, Magdi H.; Smolenski, Ryszard T.

doi:10.1080/15257770600894196

Cited by 12 publications

(9 citation statements)

References 6 publications

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“…Many of these signaling factors are similar to those found in vascular atherosclerosis and bone formation. Matrix MetalloProteinases (MMP)53, 62, Interleukin 163, Transforming growth factor-beta(TGF-beta)64, purine nucleotides42, 65, RANK66, osteoprotegrin(OPG)66, and TNF alpha67, have all been identified as signaling pathways important in the development of this disease process. Evidence, for the angiotensin converting enzyme pathway expressed and colocalize with LDL in calcified aortic valves also plays a role in future potential medical therapy68.…”

Section: Osteoblast Phenotype Is the Final Common Pathway For Aortic mentioning

confidence: 99%

Calcific Aortic Stenosis

Rajamannan

2009

ATVB

143

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Abstract-Calcific aortic stenosis is the most common indication for surgical valve replacement in the United States. For years this disease has been described as a passive degenerative process during which serum calcium attaches to the valve surface and binds to the leaflet to form nodules. Therefore, surgical treatment of this disease has been the approach toward relieving outflow obstruction in these patients. Recent studies demonstrate an association between atherosclerosis and its risk factors for aortic valve disease. In 2008, there are increasing number of epidemiology and experimental studies to provide evidence that this disease process is not a passive phenomena. There is an active cellular process that develops within the valve leaflet and causes a regulated bone formation to develop. If the atherosclerotic hypothesis is important in the initiation of aortic stenosis, then treatments used in slowing the progression of atherosclerosis may be effective in patients with aortic valve disease. This review will discuss the pathogenesis and the potential for medical therapy in the management of patients with calcific aortic stenosis by examining the lessons provided from the experimental research. Key Words: valvular heart disease Ⅲ lipids Ⅲ pathophysiology atherosclerosis Ⅲ experimental models C alcific aortic stenosis is the most common indication for surgical valve replacement in the United States. 1 With the decline of acute rheumatic fever, calcific aortic stenosis has become the most common indication for valvular disease in the United States. Landmark epidemiological studies identified risk factors for the aortic valve which are similar to those of vascular atherosclerosis, such as smoking, male gender, hypertension, elevated cholesterol levels, and renal failure. [2][3][4] For years this disease process was thought to be attributable to the build-up of nodules along the valve surface to induce a mechanical stenosis in the valve. 5 Furthermore, surgical therapy for severe symptomatic aortic stenosis is currently the only treatment option in 2008 as defined in a landmark study from 1968. 5 This study also defined the classic triad of symptoms which include chest pain, shortness of breath, and lightheadedness. This research also demonstrated that the life expectancy of this patient population is reduced significantly, if patients do not have surgical valve replacement at the onset of symptoms. 5 Currently, it is a Class I indication for surgical valve replacement according to the American Heart Association and American College of Cardiology guidelines for valvular heart disease. 6 Over the past decade, there are a growing number of studies evaluating human disease tissues to define the cellular pathways important in this calcific aortic stenosis. This review will bring together the basic science and clinical science to develop a unified approach toward treating this disease. Aortic Valve CalcificationThe presence of calcification in the aortic valve is responsible for valve stenosis. Recent descriptive ...

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Section: Osteoblast Phenotype Is the Final Common Pathway For Aortic mentioning

confidence: 99%

Calcific Aortic Stenosis

Rajamannan

2009

ATVB

143

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“…Previous studies demonstrated that statins (3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors) reduce serum low-density lipoprotein (LDL) cholesterol, which is associated with a significant reduction in cardiovascular events. [1][2][3][4] Statins also have cholesterol-independent pleiotropic effects, such as upregulation of ecto-59-nucleotidase, [5][6][7][8] activation of the phosphatidylinositol 3-kinase-Akt pathway, 9 activation of the ERK 1/2 pathway 10 and upregulation of nitric oxide (NO) synthase. 11,12 These pleiotropic actions may contribute to the cardioprotective effects of statins, such as an improved tolerance against ischemia and reperfusion injury (IR injury).…”

Section: Introductionmentioning

confidence: 99%

Short-term Statin Treatment Does Not Prevent Ischemia and Reperfusion-induced Endothelial Dysfunction in Humans

Wouters

Wever²,

Bronckers³

et al. 2012

Journal of Cardiovascular Pharmacology

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Statins are known to have cholesterol-independent pleiotropic effects, such as upregulation of the enzyme ecto-5'-nucleotidase. These effects may contribute to the protective effect of statins against ischemia and reperfusion (IR). Interestingly, pleiotropic effects have been shown to differ between hydrophilic and lipophilic statins. Flow-mediated dilation (FMD) represents a largely nitric oxide-mediated, endothelium-dependent dilation and has been shown to decrease after exposure to IR in humans. FMD has been validated to study (pharmacological) interventions in IR injury. We examined the effect of a short-term (3-7 days) statin pretreatment on brachial artery endothelial function before and after IR, and whether the effect on brachial artery endothelial function differs between rosuvastatin (hydrophilic statin) and atorvastatin (lipophilic statin). Our results show that IR significantly decreases FMD; however, statin pretreatment did not alter the effect of IR on FMD (irrespective of treatment duration or type of statin used). This experiment suggests that the cardioprotective effects of statins (both lipophilic and hydrophilic) against IR are not mediated through preservation of endothelial function.

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“…Previous studies have demonstrated that statins induce ecto-5Ј-nucletidase activation and increased interstitial adenosine formation in a setting of acute myocardial infarction in rabbits (46). Statin administration increases ATP breakdown and adenosine formation in human umbilical vein endothelial cells and human microvascular endothelial cells (34). The increased interstitial adenosine is an important trigger of K ATP channel opening (46).…”

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confidence: 99%

Effect of pravastatin on sympathetic reinnervation in postinfarcted rats

Lee¹,

Lin²,

Chang³

2007

American Journal of Physiology-Heart and Circulatory Physiology

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Lee TM, Lin MS, Chang NC. Effect of pravastatin on sympathetic reinnervation in postinfarcted rats. Am J Physiol Heart Circ Physiol 293: H3617-H3626, 2007. First published September 21, 2007; doi:10.1152/ajpheart.00875.2007.-We assessed whether pravastatin attenuates cardiac sympathetic reinnervation after myocardial infarction through the activation of ATP-sensitive K ϩ (KATP) channels. Epidemiological studies have shown that men treated with statins appear to have a lower incidence of sudden death than men without statins. However, the specific factor for this has remained disappointingly elusive. Twenty-four hours after ligation of the anterior descending artery, male Wistar rats were randomized to groups treated with either vehicle, nicorandil (a specific mitochondrial KATP channel agonist), pinacidil (a nonspecific KATP channel agonist), pravastatin, glibenclamide (a KATP channel blocker), or a combination of nicorandil and glibenclamide, pinacidil and glibenclamide, or pravastatin and glibenclamide for 4 wk. Myocardial norepinephrine levels revealed a significant elevation in vehicle-treated rats at the remote zone compared with sham-operated rats (2.54 Ϯ 0.17 vs. 1.26 Ϯ 0.36 g/g protein, P Ͻ 0.0001), consistent with excessive sympathetic reinnervation after infarction. Immunohistochemical analysis for tyrosine hydroxylase, growth-associated factor 43, and neurofilament also confirmed the change of myocardial norepinephrine. This was paralleled by a significant upregulation of tyrosine hydroxylase protein expression and mRNA in vehicle-treated rats, which was reduced after the administration of either nicorandil, pinacidil, or pravastatin. Arrhythmic scores during programmed stimulation in vehicle-treated rats were significantly higher than those treated with pravastatin. In contrast, the beneficial effects of pravastatin were reversed by the addition of glibenclamide, implicating KATP channels as the relevant target. The sympathetic reinnervation after infarction is modulated by the activation of K ATP channels. Chronic use of pravastatin after infarction, resulting in attenuated sympathetic reinnervation by the activation of K ATP channels, may modify the arrhythomogenic response to programmed electrical stimulation.immunohistochemistry; ion channels; myocardial infarction; norepinephrine; polymerase chain reaction PHARMACOLOGICAL ACTIONS of 3-hydroxy-3-methyglutaryl-CoA reductase inhibitors, commonly referred to as "statins," are not merely due to blockade of cholesterol synthesis. Statins possess important adjunctive properties that may confer additional benefits beyond changes in plasma cholesterol concentrations (25). Epidemiological studies have shown that men treated with statin administration appear to have a lower incidence of sudden death than men without statins (40). Patterson et al. (35) have shown that statins improved baroreflex sensitivity, a predictor of sudden cardiac death. There is evidence that many effects of statins are the result of reduced synthesis of isoprenoid intermediates ...

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Stimulatory Effects of Atorvastatin on Extracellular Nucleotide Degradation in Human Endothelial Cells

Cited by 12 publications

References 6 publications

Calcific Aortic Stenosis

Calcific Aortic Stenosis

Short-term Statin Treatment Does Not Prevent Ischemia and Reperfusion-induced Endothelial Dysfunction in Humans

Effect of pravastatin on sympathetic reinnervation in postinfarcted rats

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