Document Detail


Homocysteine induced arteriosclerosis-like alterations of the aorta in normotensive and hypertensive rats following application of high doses of methionine.
MedLine Citation:
PMID:  8769683     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Following oral administration of methionine in high doses to normotensive (NR) and spontaneously hypertensive (SHR) rats, its degradation product, homocysteine (HC), which is markedly elevated in serum, exerts an angiotoxic action directed to the aorta. This is accompanied by considerable loss of endothelium and degeneration, partly with dissolution of the media cells with formation of characteristic processes of the degenerating mitochondria, and by elevated HC and cystathion (CT) values in the aortic wall. At the arterial vessels of other organs similar alterations did not occur. There are quantitative differences between NR and SHR. In SHR, serum shows higher HC and CT concentrations than in NR, and the methionine-related aortic alterations are considerably more pronounced and develop earlier, with the additional formation of connective tissue. Here, a certain dependence on the methionine dose is noted, in contrast to NR, for which the magnitude of the reaction appears to be more related to the length of time of methionine application. Additional administration of atherogenic substances (cholestane-3 beta, 5 alpha, 6 beta-triol, cholesterol, angiotensin II, cholic acid with methylthiouracil) in SHR causes an exacerbation of the methionine-related aortic alterations. Only cholestane-triol has the same effect on the aortic wall in NR and SHR, with more accentuation in SHR. Cholestane-triol has, in NR as well as in SHR, a high coincidence with methionine-induced morphological reactions including the formation of mitochondrial processes. Simultaneous application of these two substances did not cause a potentiation of the effect. High doses of cholesterol bring about aortic alterations in SHR but not in NR. Thus, in addition to the disorder of fat and carbohydrate metabolism, disturbed protein metabolism is of decisive importance as a risk factor for coronary and other vascular diseases.
Authors:
D Matthias; C H Becker; R Riezler; P H Kindling
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Atherosclerosis     Volume:  122     ISSN:  0021-9150     ISO Abbreviation:  Atherosclerosis     Publication Date:  1996 May 
Date Detail:
Created Date:  1996-11-06     Completed Date:  1996-11-06     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  IRELAND    
Other Details:
Languages:  eng     Pagination:  201-16     Citation Subset:  IM    
Affiliation:
Max-Delbrück-Center for Molecular Medicine, Berline Buch, Germany.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II / pharmacology
Animals
Antilipemic Agents / pharmacology
Aorta / drug effects,  metabolism,  ultrastructure*
Arteriosclerosis / blood,  chemically induced,  pathology*
Cholestanols / pharmacology
Cholesterol / pharmacology
Cholic Acid
Cholic Acids / pharmacology
Endothelium, Vascular / pathology
Homocysteine / blood*
Hypertension / blood,  pathology*
Male
Methionine / pharmacology*
Methylthiouracil / pharmacology
Microscopy, Electron
Mitochondria / ultrastructure
Rats
Rats, Inbred SHR
Rats, Wistar
Tunica Intima / drug effects,  metabolism,  ultrastructure
Vasoconstrictor Agents / pharmacology
Chemical
Reg. No./Substance:
0/Antilipemic Agents; 0/Cholestanols; 0/Cholic Acids; 0/Vasoconstrictor Agents; 11128-99-7/Angiotensin II; 115510-05-9/cholestane-3,5,6-triol; 454-28-4/Homocysteine; 56-04-2/Methylthiouracil; 57-88-5/Cholesterol; 63-68-3/Methionine; 81-25-4/Cholic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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