Modulation by α- and γ-tocopherol and oxidized low-density lipoprotein of apoptotic signaling in human coronary smooth muscle cells∗

Nigris, Filomena de; Franconi, Flavia; Maida, Ivana; Palumbo, Giuseppe; Anania, V.; Napoli, Claudio

doi:10.1016/s0006-2952(00)00275-6

Cited by 62 publications

(53 citation statements)

References 57 publications

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“…Tissue sections (5 mm) from arterial segments were homogenized (46), and Western blot analysis was performed (47). Gels were transblotted onto nitrocellulose membranes and blocked with milk powder overnight, and samples were incubated with monoclonal antibodies (1:500 dilution for 1.5 h at room temperature) against Elk-1, p-CREB, and eNOS (epitope of NOS-III, no crossreactivity with NOS-I or -II; Santa Cruz Biotechnology) (46)(47)(48). Proteins were detected by chemiluminescence (Amersham Pharmacia Biotech enhanced chemiluminescence kit).…”

Section: Detection Of Enos Ets-like Gene-1 (Elk-1) and Phosphorylatmentioning

confidence: 99%

l -citrulline and l -arginine supplementation retards the progression of high-cholesterol-diet-induced atherosclerosis in rabbits

Hayashi

Juliet

Matsui-Hirai

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

131

117

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The objective of this study was to evaluate the influence of ingested L-arginine, L-citrulline, and antioxidants (vitamins C and E) on the progression of atherosclerosis in rabbits fed a highcholesterol diet. The fatty diet caused a marked impairment of endothelium-dependent vasorelaxation in isolated thoracic aorta and blood flow in rabbit ear artery in vivo, the development of atheromatous lesions and increased superoxide anion production in thoracic aorta, and increased oxidation-sensitive gene expression [Elk-1 and phosphorylated cAMP response element-binding protein]. Rabbits were treated orally for 12 weeks with L-arginine, L-citrulline, and͞or antioxidants. L-arginine plus L-citrulline, either alone or in combination with antioxidants, caused a marked improvement in endothelium-dependent vasorelaxation and blood flow, dramatic regression in atheromatous lesions, and decrease in superoxide production and oxidation-sensitive gene expression. These therapeutic effects were associated with concomitant increases in aortic endothelial NO synthase expression and plasma NO 2 ؊ ؉ NO 3 ؊ and cGMP levels. These observations indicate that ingestion of certain NO-boosting substances, including L-arginine, L-citrulline, and antioxidants, can abrogate the state of oxidative stress and reverse the progression of atherosclerosis. This approach may have clinical utility in the treatment of atherosclerosis in humans.antioxidant ͉ nitric oxide ͉ amino acids ͉ endothelial nitric oxide synthase A therosclerosis is an inflammatory disease (1) characterized by vascular endothelial cell dysfunction and diminished production of NO (2-5). Endothelial NO synthase (eNOS) gene transfer can reduce atherogenesis in hypercholesterolemic animals (6). NO is a widespread signaling molecule in the cardiovascular system, which functions in multiple ways to protect against the initiation and progression of atherosclerosis (7-9). For example, NO aids in preventing the adhesion and aggregation of blood cells and platelets along the endothelial cell lining in blood vessels (7,8) and is a potent inhibitor of vascular smooth muscle cell proliferation (10). NO is a potent antioxidant that can elicit antiinflammatory effects by scavenging certain reactive oxygen species (11-13), and it can prevent the oxidation of low-density lipoprotein cholesterol and thereby retard the progression of atherosclerosis (5, 14). Moreover, NO deficiency is generally associated with up-regulation of oxidation-sensitive genes, whereas increased NO production leads to decreased expression of oxidation-sensitive genes (7,15). NO is synthesized by NOS, which utilizes L-arginine as substrate and produces L-citrulline as the second reaction product. L-arginine can be synthesized from L-citrulline in endothelial and other cell types, thereby providing a recycling pathway for the conversion of L-citrulline to NO via L-arginine (16)(17)(18)(19).The oral administration of L-arginine to animals (7, 12, 20-26) and humans (5,8,(27)(28)(29) has been demonstrated to slow the progressi...

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Section: Detection Of Enos Ets-like Gene-1 (Elk-1) and Phosphorylatmentioning

confidence: 99%

l -citrulline and l -arginine supplementation retards the progression of high-cholesterol-diet-induced atherosclerosis in rabbits

Hayashi

Juliet

Matsui-Hirai

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

131

117

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“…Thus, NCX-4016 has a potent antioxidant effect also in the atherosclerotic lesions of mice probably by means of scavenging of the radical-induced oxidation of LDL also in the arterial wall. Oxidized LDL may induce apoptosis in human coronary cells (7,8). This phenomenon may favor the development of unstable atherosclerotic lesions (7,8).…”

Section: Discussionmentioning

confidence: 99%

“…Oxidized LDL may induce apoptosis in human coronary cells (7,8). This phenomenon may favor the development of unstable atherosclerotic lesions (7,8). However, apoptosis in macrophages also may reduce a potential source of mediators which can contribute to destabilizing the plaque (e.g., metalloproteinases and MCP-1).…”

Section: Discussionmentioning

confidence: 99%

“…5,6). Recent data indicate that LDL oxidation may promote per se activation of several signaling pathways and transcription factors in human coronary arteries (7)(8)(9). Several of these pathways are reduced by concomitant administration of vitamin E (7,9).…”

mentioning

confidence: 99%

“…Recent data indicate that LDL oxidation may promote per se activation of several signaling pathways and transcription factors in human coronary arteries (7)(8)(9). Several of these pathways are reduced by concomitant administration of vitamin E (7,9). Thus, compounds with antioxidant properties may reduce downstream effects induced by LDL oxidation in the arterial wall, and this phenomenon could retard the progression of atherosclerosis.…”

mentioning

confidence: 99%

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Chronic treatment with nitric oxide-releasing aspirin reduces plasma low-density lipoprotein oxidation and oxidative stress, arterial oxidation-specific epitopes, and atherogenesis in hypercholesterolemic mice

Napoli

Ackah

Nigris

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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The effects of chronic treatment with nitric oxide-containing aspirin (NO-aspirin, NCX-4016) in comparison with regular aspirin or placebo on the development of a chronic disease such as atherosclerosis were investigated in hypercholesterolemic low-density lipoprotein (LDL)-receptor-deficient mice. Male mice were assigned randomly to receive in a volume of 10 ml͞kg either placebo (n ‫؍‬ 10), 30 mg͞kg͞day NO-aspirin (n ‫؍‬ 10), or 18 mg͞kg͞day of regular aspirin (n ‫؍‬ 10). After 12 weeks of treatment, the computerassisted imaging analysis revealed that NO-aspirin reduced the aortic cumulative lesion area by 39.8 ؎ 12.3% compared with that of the placebo (P < 0.001). Regular aspirin did not reduce significantly aortic lesions (؊5.1 ؎ 2.3%) compared with the placebo [P ‫؍‬ 0.867, not significant (NS)]. Furthermore, NO-aspirin reduced significantly plasma LDL oxidation compared with aspirin and placebo, as shown by the significant reduction of malondialdehyde content (P < 0.001) as well as by the prolongation of lag-time (P < 0.01). Similarly, systemic oxidative stress, measured by plasma isoprostanes, was significantly reduced by treatment with NCX-4016 (P < 0.05). More importantly, mice treated with NO-aspirin revealed by immunohistochemical analysis of aortic serial sections a significant decrease in the intimal presence of oxidation-specific epitopes of oxLDL (E06 monoclonal antibody, P < 0.01), and macrophages-derived foam cells (F4͞80 monoclonal antibody, P < 0.05), compared with placebo or aspirin. These data indicate that enhanced NO release by chronic treatment with the NO-containing aspirin has antiatherosclerotic and antioxidant effects in the arterial wall of hypercholesterolemic mice.atherosclerosis ͉ LDL-receptor-deficient mice

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Assessing Mitochondrial Redox Status by Flow Cytometric Methods: Vascular Response to Fluid Shear Stress

Jen

et al. 2011

CP Cytometry

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Mitochondria are an important source of superoxide production contributing to physiological and pathological responses, including vascular oxidative stress that is relevant to cardiovascular diseases. Vascular oxidative stress is intimately linked with pro‐inflammatory states and atherosclerosis. Oxidized low‐density lipoprotein (OxLDL) modulates intracellular redox status and induces apoptosis in endothelial cells. Hemodynamic, specifically, fluid shear stress imparts both biomechanical and metabolic effects on vasculature. Mitochondria are an important source of superoxide production contributing to vascular oxidative stress with relevance to cardiovascular diseases. We hereby present biophysical and biochemical approaches, including fluorescence‐activated cell sorting, to assess the dynamics of vascular redox status. Curr. Protoc. Cytom. 58:9.37.1‐9.37.14. © 2011 by John Wiley & Sons, Inc.

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Modulation by α- and γ-tocopherol and oxidized low-density lipoprotein of apoptotic signaling in human coronary smooth muscle cells∗

Cited by 62 publications

References 57 publications

l -citrulline and l -arginine supplementation retards the progression of high-cholesterol-diet-induced atherosclerosis in rabbits

l -citrulline and l -arginine supplementation retards the progression of high-cholesterol-diet-induced atherosclerosis in rabbits

Chronic treatment with nitric oxide-releasing aspirin reduces plasma low-density lipoprotein oxidation and oxidative stress, arterial oxidation-specific epitopes, and atherogenesis in hypercholesterolemic mice

Assessing Mitochondrial Redox Status by Flow Cytometric Methods: Vascular Response to Fluid Shear Stress

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