Aspirin inhibits ox-LDL-mediated LOX-1 expression and metalloproteinase-1 in human coronary endothelial cells

Mehta, Jawahar L.; Chen, J.; Yu, Fangming; Li, D.Y.

doi:10.1016/j.cardiores.2004.07.002

Cited by 106 publications

(70 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…LOX-1 activation has also been shown to activate NADPH oxidase and subsequent redox signals involving MAPKs and NF-B in human endothelial cells. 14,38 We found that the small proangiogenic concentrations of oxLDL that led to LOX-1 expression also induced NADPH oxidase (both gp91 phox and p47 phox subunits), activated MAPK (both p38 and p44/42 components) and NF-B p65, and resulted in VEGF expression. Our experiments show that VEGF expression induced by oxLDL is a major mechanism of capillary tube formation from HCAECs.…”

Section: Discussionmentioning

confidence: 86%

“…Previous studies have demonstrated that LOX-1 activation induces oxidative stress 10 and oxidative stress in turn stimulates LOX-1 expression, 14 suggesting a positive feedback loop between oxidative stress and LOX-1 expression. LOX-1 activation has also been shown to activate NADPH oxidase and subsequent redox signals involving MAPKs and NF-B in human endothelial cells.…”

Section: Discussionmentioning

confidence: 98%

“…14 oxLDL was kept in 50 mol/L Tris-HCl, 0.15 mol/L NaCl and 2 mol/L EDTA at pH 7.4 and used within 10 days of preparation.…”

Section: Preparation Of Lipoproteinsmentioning

confidence: 99%

See 2 more Smart Citations

Small Concentrations of oxLDL Induce Capillary Tube Formation From Endothelial Cells via LOX-1–Dependent Redox-Sensitive Pathway

Dandapat

Sun

et al. 2007

ATVB

140

116

View full text Add to dashboard Cite

Objective-Vascular endothelial growth factor (VEGF), a key angiogenic growth factor, stimulates angiogenesis. Low levels of reactive oxygen species (ROS) function as signaling molecules for angiogenesis. We postulated that low concentrations of oxLDL might induce low levels of ROS and initiate angiogenesis. Methods and Results-An in vitro model of tube formation from human coronary artery endothelial cells (HCAECs) was used.oxLDL (0.1, 1, 2, 5 g/mL) induced VEGF expression and enhanced tube formation. oxLDL-mediated VEGF expression and tube formation were suppressed by a specific blocking anti-LOX-1 antibody. Anti-LOX-1 antibody also reduced oxLDL-induced increase in the expression of NADPH oxidase (gp91 phox and p47 phox subunits) and subsequent intracellular ROS generation, phosphorylation of p38 as well as p44/42MAPK, and NF-B p65 expression. gp91 phox siRNA had a similar effect. The expression of VEGF and NF-B p65 induced by oxLDL was also inhibited by the specific extracellular signal-regulated kinase (ERK) 1/2 inhibitor U0126 and the p38 MAPK inhibitor SB203580. Importantly, the NADPH oxidase inhibitor apocynin, gp91 phox siRNA, U0126, and SB203580 all reduced tube formation in response to oxLDL. Conclusions-These

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Small Concentrations of oxLDL Induce Capillary Tube Formation From Endothelial Cells via LOX-1–Dependent Redox-Sensitive Pathway

Dandapat

Sun

et al. 2007

ATVB

140

116

View full text Add to dashboard Cite

show abstract

“…Experimentally, however, no studies have been performed to investigate the potential use of NSAIDs as MMPs inhibitors in the MI setting. Aspirin, the most commonly used NSAID among patients with myocardial infarction and heart failure, suppresses MMP-1 in isolated human coronary endothelial cells but did not affect MMP-2 or -9 levels [140,141].…”

Section: 25mentioning

confidence: 93%

Matrix Metalloproteinases: Drug Targets for Myocardial Infarction

Yabluchanskiy¹,

Li²,

Chilton³

et al. 2013

CDT

View full text Add to dashboard Cite

Myocardial infarction (MI) remains a major cause of morbidity and mortality worldwide. Rapid advances in the treatment of acute MI have significantly improved short-term outcomes in patient, due in large part to successes in preventing myocardial cell death and limiting infarct area during the time of ischemia and subsequent reperfusion. Matrix metalloproteases (MMPs) play key roles in post-MI cardiac remodeling and in the development of adverse outcomes. This review highlights the importance of MMPs in the injury and remodeling response of the left ventricle and also discusses their potential as therapeutic targets Additional pre-clinical and clinical research is needed to further investigate and understand the cardioprotective effects of MMPs inhibitors.

show abstract

“…We have observed that aspirin, in a dose-and timedependent fashion, reduced ox-LDL-mediated LOX-1 expression, MMP-1 expression and activity, p38MAPK activation and superoxide anion generation in human coronary artery endothelial cells (15). Interestingly, we have observed that the treatment of human coronary artery endothelial cells with salicylate, but not indomethacin, resulted in effects similar to those of aspirin (15).…”

Section: Effect On Oxidative Stressmentioning

confidence: 72%

Relevance of Platelet-independent Effects of Aspirin to Its Salutary Effect in Atherosclerosis-related Events

Khan¹,

Mehta²

2005

JAT

View full text Add to dashboard Cite

There is a close inter-relationship between oxidative stress, coagulation, inflammation, and smooth muscle cell growth as key components of atherosclerosis (Fig. 1). As an analgesic and anti-pyretic, aspirin has been in use for over a century. It acetylates the COX enzyme, irreversibly inhibiting the formation of prostaglandin. Its action on platelet TxA2 has highlighted its role as an anti-thrombotic agent in cardiovascular patients. Over the last two decades, unique anti-inflammatory properties of aspirin not shared by other non-steroidals have been discovered. Aspirin biotransforms into salicylate, which has diverse but potent anti-inflammatory properties. As we strive to better understand the concepts of atherogenesis, chronic inflammation, oxidative stress, and endothelial activation, these novel effects of aspirin provide new insights as to how this wonder drug works. These effects of aspirin alter many, if not all, components of the atherogenesis cascade shown in Fig. 1

show abstract

Aspirin inhibits ox-LDL-mediated LOX-1 expression and metalloproteinase-1 in human coronary endothelial cells

Cited by 106 publications

References 41 publications

Small Concentrations of oxLDL Induce Capillary Tube Formation From Endothelial Cells via LOX-1–Dependent Redox-Sensitive Pathway

Small Concentrations of oxLDL Induce Capillary Tube Formation From Endothelial Cells via LOX-1–Dependent Redox-Sensitive Pathway

Matrix Metalloproteinases: Drug Targets for Myocardial Infarction

Relevance of Platelet-independent Effects of Aspirin to Its Salutary Effect in Atherosclerosis-related Events

Contact Info

Product

Resources

About