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Conference Paper: The Endothelial Saga: From Function to Dysfunction
Title | The Endothelial Saga: From Function to Dysfunction |
---|---|
Authors | |
Issue Date | 2014 |
Publisher | The Japanese Pharmacological Society (JPS). |
Citation | The 87th Annual Meeting of The Japanese Pharmacological Society (JPS), Sendai, Japan, 19-21 March 2014 How to Cite? |
Abstract | Endothelium-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. |
Description | Conference Theme: Resilience, Ingenuity, and Rebirth JPS Plenary Lecture |
Persistent Identifier | http://hdl.handle.net/10722/204443 |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Vanhoutte, PMGR | en_US |
dc.date.accessioned | 2014-09-19T23:52:21Z | - |
dc.date.available | 2014-09-19T23:52:21Z | - |
dc.date.issued | 2014 | en_US |
dc.identifier.citation | The 87th Annual Meeting of The Japanese Pharmacological Society (JPS), Sendai, Japan, 19-21 March 2014 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/204443 | - |
dc.description | Conference Theme: Resilience, Ingenuity, and Rebirth | - |
dc.description | JPS Plenary Lecture | - |
dc.description.abstract | Endothelium-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.language | eng | en_US |
dc.publisher | The Japanese Pharmacological Society (JPS). | - |
dc.relation.ispartof | Annual Meeting of The Japanese Pharmacological Society (JPS) | en_US |
dc.title | The Endothelial Saga: From Function to Dysfunction | en_US |
dc.type | Conference_Paper | en_US |
dc.identifier.email | Vanhoutte, PMGR: vanhoutt@hku.hk | en_US |
dc.identifier.authority | Vanhoutte, PMGR=rp00238 | en_US |
dc.description.nature | published_or_final_version | - |
dc.identifier.hkuros | 238776 | en_US |
dc.publisher.place | Japan | - |