Journal article
Endothelial function in the time of the giants
Journal of cardiovascular pharmacology, Vol.52(5), pp.385-392
11/2008
DOI: 10.1097/FJC.0b013e31818a403b
PMCID: PMC2869214
PMID: 19033817
Abstract
Paul Vanhoutte is one of the fathers of vascular biology. Among his great contributions, he demonstrated that endothelium modulates vasomotor response to vasoactive products (including serotonin) that are released when platelets aggregate in an artery. He found in arteries ex vivo that when endothelium is dysfunctional, in atherosclerosis or hypertension, normal relaxation to aggregation of platelets is impaired and vessels may contract. He proposed that this mechanism may predispose to vasospasm. The results of our experiments in vivo indicate that atherosclerosis greatly potentiates vasoconstrictor responses to serotonin in the limb, brain, and eye of monkeys. We proposed that transient ischemic attacks may be mediated by platelet-induced vasospasm. We observed endothelial dysfunction in atherosclerotic monkeys, with improvement of endothelial function when hypercholesterolemia was corrected. Recently, we studied the aortic valve, which has unique endothelium, in hypercholesterolemic mice to examine the pathophysiology of aortic valvular stenosis. Oxidative stress is increased in stenotic valves, and severe aortic stenosis develops in about one third of old, hypercholesterolemic mice. In stenotic aortic valves from humans, there is increased oxidative stress near calcified regions of the valves. Oxidative stress may trigger expression of pro-calcific genes in the aortic valve. Finally, we have used gene transfer of extracellular superoxide dismutase (ecSOD) to study endothelial effects of oxidative stress. Gene transfer of normal ecSOD improves endothelial dysfunction in several disease states, but gene transfer of ecSOD(R213G), a gene variant of ecSOD that is common in humans, fails to improve endothelial function. Gene transfer approaches may be useful to study mechanisms by which gene variants predispose to endothelial dysfunction and vascular disease.
Details
- Title: Subtitle
- Endothelial function in the time of the giants
- Creators
- Donald D Heistad - From the Cardiovascular Center and Departments of Internal Medicine and Pharmacology, University of Iowa Carver College of Medicine and VA Medical Center Iowa City, Iowa 52242-1081, USA. donald-heistad@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Journal of cardiovascular pharmacology, Vol.52(5), pp.385-392
- DOI
- 10.1097/FJC.0b013e31818a403b
- PMID
- 19033817
- PMCID
- PMC2869214
- NLM abbreviation
- J Cardiovasc Pharmacol
- ISSN
- 0160-2446
- eISSN
- 1533-4023
- Publisher
- United States
- Grant note
- P01 NS024621-220019 / NINDS NIH HHS NS-24621 / NINDS NIH HHS P01 NS024621 / NINDS NIH HHS P01 HL062984 / NHLBI NIH HHS HL-62984 / NHLBI NIH HHS P01 HL062984-080002 / NHLBI NIH HHS
- Language
- English
- Date published
- 11/2008
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040312802771
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