+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

RAGE, vascular tone and vascular disease

RAGE, vascular tone and vascular disease

Pharmacology & Therapeutics 124(2): 185-194

Evidence provided by both clinical and pre-clinical studies regarding a central involvement of the receptor for advanced glycation endproducts (RAGE) in vascular disease continues to mount. RAGE is upregulated as a consequence of activation of the ubiquitous pro-inflammatory transcription factor NF-kappaB which is activated in response to diverse inflammatory stimuli including hyperglycaemia, oxidised low density lipoprotein (oxLDL) and reduced shear stress. RAGE may maintain and amplify inflammatory responses in the vasculature if ligand for the receptor is present. RAGE binding by circulating advanced glycation endproducts (AGEs) or S100 protein released by activated leukocytes results in the generation of reactive oxygen species (ROS) and further activation of NF-kappaB. This leads to upregulation of adhesion molecules for circulating monocytes as well as further upregulation of RAGE itself. In addition, these ROS may scavenge and reduce bioavailability of the labile vasodilator nitric oxide (NO), reducing its anti-inflammatory effects and possibly compromising control of vascular tone directly. In addition to atherosclerosis and vascular diseases associated with diabetes, recent data from studies in transgenic mice overexpressing the RAGE ligand S100A4/MTS1 suggest a role for RAGE in the pathogenesis of pulmonary arterial hypertension (PAH). RAGE antagonism also prevents proliferation and migration of pulmonary arterial smooth muscle cells in response to 5-HT, suggesting that S100-RAGE signalling may be of key importance in pulmonary vascular homeostasis and/or disease. Further study of the role of RAGE in inflammation seems likely to yield, not only promising therapeutics but key insights into the pathophysiology of vascular disease as well.

(PDF emailed within 0-6 h: $19.90)

Accession: 055333020

Download citation: RISBibTeXText

PMID: 19616578

DOI: 10.1016/j.pharmthera.2009.06.013

Related references

Human perivascular adipose tissue dysfunction as a cause of vascular disease: Focus on vascular tone and wall remodeling. European Journal of Pharmacology 766: 16-24, 2016

Cellular and molecular mechanisms regulating vascular tone. Part 1: basic mechanisms controlling cytosolic Ca2+ concentration and the Ca2+-dependent regulation of vascular tone. Journal of Anesthesia 21(2): 220-231, 2007

Role of endothelium-derived relaxing factor in regulation of vascular tone and remodeling. Update on humoral regulation of vascular tone. Hypertension 17(6 Pt 2): 909-916, 1991

Systemic activation of the calcium sensing receptor produces acute effects on vascular tone and circulatory function in uremic and normal rats: focus on central versus peripheral control of vascular tone and blood pressure by cinacalcet. Journal of Pharmacology and Experimental Therapeutics 323(1): 217-226, 2007

Value of the endothelium-derived relaxant factor as a mediator in vascular regulation. Effect of the vascular endothelium on vascular tone and thrombocyte function. Fortschritte der Medizin 106(20): 428-430, 1988

Diabetic vascular disease: it's all the RAGE. Antioxidants & Redox Signaling 7(11-12): 1588-1600, 2005

The next generation of RAGE modulators: implications for soluble RAGE therapies in vascular inflammation. Journal of Molecular Medicine 91(12): 1329-1331, 2014

RAGE: a novel biological and genetic marker for vascular disease. Clinical Science 116(8): 621-637, 2009

Low k m cyclic amp phosphodiesterase isozymes and modulation of tone in vascular airway and modulation of tone in vascular airway and gastrointestinal smooth muscle. Jacobson, K A , J W Daly And V Manganiello (Ed ) Purines in Cellular Signaling: Targets For New Drugs; Conference, Rockville, Maryland, Usa, September 17-20, 1989 Xv+448p Springer-Verlag New York, Inc : Secaucus, New Jersey, Usa; Berlin, West Germany Illus 358-364, 1990

RAGE: a novel target for drug intervention in diabetic vascular disease. Pharmaceutical Research 21(7): 1079-1086, 2004

Level of vascular tone as a factor of reactivity of smooth muscle vascular structures. Kardiologiya 17(10): 98-103, 1977

Effect of angiotensin and vasopressin on the vascular territory of the mesentery dependant on vascular tone in the dog. Therapie 22(6): 1369-1376, 1967

Vascular adaptations to hypoxia: molecular and cellular mechanisms regulating vascular tone. Essays in Biochemistry 43: 105-119, 2007

Vascular tone and reactivity to serotonin in the internal and external carotid vascular beds of the dog. Journal of Pharmacology and Experimental Therapeutics 197(1): 49-56, 1976

Vascular KCNQ channels in humans: the sub-threshold brake that regulates vascular tone?. British Journal of Pharmacology 162(1): 38-41, 2011