File Download
Supplementary

Conference Paper: The Endothelial Saga: From Function to Dysfunction

TitleThe Endothelial Saga: From Function to Dysfunction
Authors
Issue Date2014
PublisherThe Japanese Pharmacological Society (JPS).
Citation
The 87th Annual Meeting of The Japanese Pharmacological Society (JPS), Sendai, Japan, 19-21 March 2014 How to Cite?
AbstractEndothelium-dependent dilatations are due mainly to the release of nitric oxide (NO) which is formed by the constitutive endothelial NO synthase (eNOS). NO diffuses to the underlying vascular smooth muscle and stimulates soluble guanylyl cyclase with the resulting production of cyclic GMP. The release of NO from the endothelium can be mediated by both pertussis toxin-sensitive Gi - (e.g. α2-adrenergic agonists, serotonin) and insensitive Gq- (adenosine diphosphate, bradykinin) proteins. The ability of the endothelial cell to release NO can be down-regulated by oxidative stress and increased presence of oxidized low density lipoproteins (LDL). It is reduced chronically by aging, smoking, environmental pollution and in hypertension and diabetes. Following injury or apoptotic death, the endothelium regenerates. However, in regenerated endothelial cells, there is an early selective loss of the pertussis-toxin sensitive mechanisms of NO-release. Functional studies suggest that abnormal handling of LDL because of increased oxidative stress play a key role in this selective loss. Genomic analysis demonstrates the emergence of fatty acid binding protein-A (A-FABP)) in regenerated endothelial cells. To verify the role of oxidative stress and A-FABP in the genesis of coronary atherosclerosis, endothelial regeneration was induced in the coronary artery of pigs treated chronically with BMS309403 (A-FABP inhibitor) or apocynin (anti-oxidant) for 28 days before functional examination and histological analysis of the coronary arteries (with native or regenerated endothelium). Both the antioxidant treatment and inhibition of A-FABP normalized the diminished Gi -protein mediated relaxations to serotonin and reduced the intima-medial thickening caused by endothelial regeneration. These treatments did not affect the response to bradykinin or endothelium-independent agonists (detaNONOate and isoproterenol). These experiments confirm the crucial role of oxidative stress and of the emergence of A-FABP in the initiation of endothelial dysfunction and subsequent coronary atherosclerosis.
DescriptionConference Theme: Resilience, Ingenuity, and Rebirth
JPS Plenary Lecture
Persistent Identifierhttp://hdl.handle.net/10722/204443

 

DC FieldValueLanguage
dc.contributor.authorVanhoutte, PMGRen_US
dc.date.accessioned2014-09-19T23:52:21Z-
dc.date.available2014-09-19T23:52:21Z-
dc.date.issued2014en_US
dc.identifier.citationThe 87th Annual Meeting of The Japanese Pharmacological Society (JPS), Sendai, Japan, 19-21 March 2014en_US
dc.identifier.urihttp://hdl.handle.net/10722/204443-
dc.descriptionConference Theme: Resilience, Ingenuity, and Rebirth-
dc.descriptionJPS Plenary Lecture-
dc.description.abstractEndothelium-dependent dilatations are due mainly to the release of nitric oxide (NO) which is formed by the constitutive endothelial NO synthase (eNOS). NO diffuses to the underlying vascular smooth muscle and stimulates soluble guanylyl cyclase with the resulting production of cyclic GMP. The release of NO from the endothelium can be mediated by both pertussis toxin-sensitive Gi - (e.g. α2-adrenergic agonists, serotonin) and insensitive Gq- (adenosine diphosphate, bradykinin) proteins. The ability of the endothelial cell to release NO can be down-regulated by oxidative stress and increased presence of oxidized low density lipoproteins (LDL). It is reduced chronically by aging, smoking, environmental pollution and in hypertension and diabetes. Following injury or apoptotic death, the endothelium regenerates. However, in regenerated endothelial cells, there is an early selective loss of the pertussis-toxin sensitive mechanisms of NO-release. Functional studies suggest that abnormal handling of LDL because of increased oxidative stress play a key role in this selective loss. Genomic analysis demonstrates the emergence of fatty acid binding protein-A (A-FABP)) in regenerated endothelial cells. To verify the role of oxidative stress and A-FABP in the genesis of coronary atherosclerosis, endothelial regeneration was induced in the coronary artery of pigs treated chronically with BMS309403 (A-FABP inhibitor) or apocynin (anti-oxidant) for 28 days before functional examination and histological analysis of the coronary arteries (with native or regenerated endothelium). Both the antioxidant treatment and inhibition of A-FABP normalized the diminished Gi -protein mediated relaxations to serotonin and reduced the intima-medial thickening caused by endothelial regeneration. These treatments did not affect the response to bradykinin or endothelium-independent agonists (detaNONOate and isoproterenol). These experiments confirm the crucial role of oxidative stress and of the emergence of A-FABP in the initiation of endothelial dysfunction and subsequent coronary atherosclerosis.-
dc.languageengen_US
dc.publisherThe Japanese Pharmacological Society (JPS).-
dc.relation.ispartofAnnual Meeting of The Japanese Pharmacological Society (JPS)en_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleThe Endothelial Saga: From Function to Dysfunctionen_US
dc.typeConference_Paperen_US
dc.identifier.emailVanhoutte, PMGR: vanhoutt@hku.hken_US
dc.identifier.authorityVanhoutte, PMGR=rp00238en_US
dc.description.naturepublished_or_final_version-
dc.identifier.hkuros238776en_US
dc.publisher.placeJapan-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats