Atorvastatin inhibits the expression of RAGE induced by advanced glycation end products on aortas in healthy Sprague–Dawley rats

Liu, Xu; Zang, Panpan; Feng, Bo; Qian, Qiaohui

doi:10.1186/1758-5996-6-102

Cited by 30 publications

(21 citation statements)

References 35 publications

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“…The half-life of AGEs is about double that of the average cell life, meaning that damage can persist for quite some time, especially in long-lived cells like nerve and brain cells, eye and collagen proteins, although the body is able to handle AGEs slowly. The pathophysiological function of AGEs has been implicated in the progression of aging and age-related diseases including Alzheimer's (Vitek et al 1994;Salahuddin et al 2014), Parkinson's disease (Salahuddin et al 2014), atherosclerosis-related diseases (cardiovascular diseases and stroke) (Chappey et al 1997;Moriya et al 2014;Pertynska-Marczewska andMerhi 2014, 2014;Xu et al 2014). The mechanism with AGEs-pathogenesis is through a process called cross linking that causes intracellular damage and apoptosis.…”

Section: Ages and Ragementioning

confidence: 98%

Role of RAGE in Alzheimer’s Disease

et al. 2015

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Receptor for advanced glycation end products (RAGE) is a receptor of the immunoglobulin super family that plays various important roles under physiological and pathological conditions. Compelling evidence suggests that RAGE acts as both an inflammatory intermediary and a critical inducer of oxidative stress, underlying RAGE-induced Alzheimer-like pathophysiological changes that drive the process of Alzheimer's disease (AD). A critical role of RAGE in AD includes beta-amyloid (Aβ) production and accumulation, the formation of neurofibrillary tangles, failure of synaptic transmission, and neuronal degeneration. The steady-state level of Aβ depends on the balance between production and clearance. RAGE plays an important role in the Aβ clearance. RAGE acts as an important transporter via regulating influx of circulating Aβ into brain, whereas the efflux of brain-derived Aβ into the circulation via BBB is implemented by LRP1. RAGE could be an important contributor to Aβ generation via enhancing the activity of β- and/or γ-secretases and activating inflammatory response and oxidative stress. However, sRAGE-Aβ interactions could inhibit Aβ neurotoxicity and promote Aβ clearance from brain. Meanwhile, RAGE could be a promoting factor for the synaptic dysfunction and neuronal circuit dysfunction which are both the material structure of cognition, and the physiological and pathological basis of cognition. In addition, RAGE could be a trigger for the pathogenesis of Aβ and tau hyper-phosphorylation which both participate in the process of cognitive impairment. Preclinical and clinical studies have supported that RAGE inhibitors could be useful in the treatment of AD. Thus, an effective measure to inhibit RAGE may be a novel drug target in AD.

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Section: Ages and Ragementioning

confidence: 98%

Role of RAGE in Alzheimer’s Disease

et al. 2015

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“…114 Atorvastatin downregulates the expression of RAGE in vitro. 115 Angiotensin II receptor blockers, telmisartan, and candesartan downregulates the RAGE expression. 116,117 Thiazolidinediones reduce the expression of RAGE in the endothelium.…”

Section: Downregulation Of Rage Expressionmentioning

confidence: 99%

Do Advanced Glycation End Products and Its Receptor Play a Role in Pathophysiology of Hypertension?

Prasad

Mishra

2017

Int J Angiol

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Hypertension (HTN) accounts for 6% of death worldwide. The prevalence of HTN varies being lowest in rural India (3.4% in men and 6.8% in women), and highest in Poland (68.9% in men and 72.5% in women).1 Prevalence of HTN was 27.1% in men and 30.1% in women in the adult population of United States. 1HTN is a risk factor for cardiovascular diseases including stroke and myocardial infarction. There are two types of HTN. Primary or essential which accounts for 90 to 95% and its etiology is not known. Secondary HTN which accounts for 5 to 10% and its etiology is known.Advanced glycation end products (AGEs) and its cellular receptor (RAGE) may play a role in the pathophysiology of HTN. Interaction of AGEs with RAGE increases the expression and release of inflammatory cytokines, generation of reactive oxygen species (ROS), and activates nuclear factor kappa-B (NF-κB).2-4 These agents might affect the structures of arterial wall and/or produce contraction of the arterial wall. Various measures are available for the prevention and treatment of HTN. 5 However, very little attention has been given to the role of AGEs and its receptors in initiation and maintenance of arterial stiffness and HTN. Keywords► advanced glycation end products ► receptor for AGE ► soluble receptor for AGE ► hypertension ► arterial stiffness ► management of hypertension AbstractThere is a close relationship between arterial stiffness and blood pressure. The studies suggest that the advanced glycation end products (AGEs) and its cell receptor (RAGE) are involved in the arterial stiffness in two ways: changes in arterial structure and vascular function. Plasma levels of AGEs and expression of RAGE are elevated, while the levels of soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) are lowered in patients with hypertension (HTN). There is a positive correlation between plasma levels of AGEs and arterial stiffness, and an inverse association between arterial stiffness/HTN, and serum levels of sRAGE and esRAGE. Various measures can reduce the levels of AGEs and expression of RAGE, and elevate sRAGE. Arterial stiffness and blood pressure could be reduced by lowering the serum levels of AGEs, and increasing the levels of sRAGE. Levels of AGEs can be lowered by reducing the consumption of AGE-rich diet, short duration of cooking in moist heat at low temperature, and cessation of cigarette smoking. Drugs such as aminoguanidine, vitamins, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor blockers, statins, and metformin inhibit AGE formation. Alagebrium, an AGE breakers reduces levels of AGEs. Clinical trials with some drugs tend to reduce stiffness. Systemic administration of sRAGE has beneficial effect in animal studies. In conclusion, AGE-RAGE axis is involved in arterial stiffness and HTN. The studies suggest that inhibition of AGEs formation, reduction of AGE consumption, blockade of AGE-RAGE interaction, suppression of RAGE expression, and exogenous administration of sRAGE may be novel therapeutic strategies for treatment...

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“…Statins (simvastatin, atorvastatin), 106,107 angiotensin-II receptor blockers (candesartan, telmisartan), 108,109 calcium channel blocker (nifedipine), 110 antidiabetic agents (pioglitazone, rosiglitazone), 111 and curcumin 112 downregulate the expression of RAGE. Azeliragon (TTP488) inhibits interaction of RAGE with AGE and other RAGE ligands.…”

Section: Suppression Of Rage Expressions and Rage Blockersmentioning

confidence: 99%

AGE-RAGE Axis in the Pathophysiology of Chronic Lower Limb Ischemia and a Novel Strategy for Its Treatment

Prasad

Bhanumathy

2020

Int J Angiol

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This review focuses on the role of advanced glycation end products (AGEs) and its cell receptor (RAGE) and soluble receptor (sRAGE) in the pathogenesis of chronic lower limb ischemia (CLLI) and its treatment. CLLI is associated with atherosclerosis in lower limb arteries. AGE-RAGE axis which comprises of AGE, RAGE, and sRAGE has been implicated in atherosclerosis and restenosis. It may be involved in atherosclerosis of lower limb resulting in CLLI. Serum and tissue levels of AGE, and expression of RAGE are elevated, and the serum levels of sRAGE are decreased in CLLI. It is known that AGE, and AGE-RAGE interaction increase the generation of various atherogenic factors including reactive oxygen species, nuclear factor-kappa B, cell adhesion molecules, cytokines, monocyte chemoattractant protein-1, granulocyte macrophage-colony stimulating factor, and growth factors. sRAGE acts as antiatherogenic factor because it reduces the generation of AGE-RAGE-induced atherogenic factors. Treatment of CLLI should be targeted at lowering AGE levels through reduction of dietary intake of AGE, prevention of AGE formation and degradation of AGE, suppression of RAGE expression, blockade of AGE-RAGE binding, elevation of sRAGE by upregulating sRAGE expression, and exogenous administration of sRAGE, and use of antioxidants. In conclusion, AGE-RAGE stress defined as a shift in the balance between stressors (AGE, RAGE) and antistressor (sRAGE) in favor of stressors, initiates the development of atherosclerosis resulting in CLLI. Treatment modalities would include reduction of AGE levels and RAGE expression, RAGE blocker, elevation of sRAGE, and antioxidants for prevention, regression, and slowing of progression of CLLI.

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Atorvastatin inhibits the expression of RAGE induced by advanced glycation end products on aortas in healthy Sprague–Dawley rats

Cited by 30 publications

References 35 publications

Role of RAGE in Alzheimer’s Disease

Role of RAGE in Alzheimer’s Disease

Do Advanced Glycation End Products and Its Receptor Play a Role in Pathophysiology of Hypertension?

AGE-RAGE Axis in the Pathophysiology of Chronic Lower Limb Ischemia and a Novel Strategy for Its Treatment

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