liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Apolipoprotein A-1 derived amyloid in the atherosclerotic intima of the human aorta
Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Amyloid is insoluble fibrillar protein deposited in the extracellular space. The resulting heterogeneous group of disorders, amyloidosis, can be sporadic or hereditary, and the amyloid is systemically distributed or localized in single organs. Systemic hereditary amyloidoses are disorders caused by mutant forms of plasma proteins such as transthyretin (TTR) or less frequently, apolipoprotein A-1 (apo A-1), the major protein in high-density lipoprotein (HDL). Local deposition of amyloid associated with aging may be pathogenically important in Alzheimer's disease and type II diabetes. Localized amyloid in the medial and intimal layer of the aorta, commonly found in elderly humans, is of unknown sigoificance. The aim of this work was to investigate the nature of amyloid in the atherosclerotic intima of the human aorta, its fibrillogenesis and potential pathogenic importance. Two biochemically different forms of localized amyloid deposits in the aorta were identified; one affecting the atherosclerotic plaques of the intima and the other the media. Amyloid fibrils from the media has subse quently been found to consist of a protein fragment derived from lactadherin. Purified amyloid protein from atherosclerotic plaques of aortas in utopsy cases was shown by amino acid sequence analysis to be derived from apo A-1. Apo A-1 derived amyloid was immunohistochemically confirmed in 14% of 72 autopsy cases. A mutation was found in the apo A-1 gene (Δ Lys 1 07) in one of the 9 cases with intimal amyloid. Thus wild type, as well as mutant apo A-1, is amyloidogenic in humans. There was a tendency towards higher plasma levels of apo A-1 in patients with apo A-1 derived amyloid who underwent arterial reconstruction, compared to those without amyloid (p= 0.055). Levels of LDL- and total cholesterol were higher in the group with amyloid. Atherosclerosis induces high concentration of the acute phase reactant SAA in atherosclerotic lesions. SAA may displace apo A-1 from HDL, which, in addition to high levels of plasma apo A-1, could lead to an increased concentration oflipid free apo A-1 in the intima. Conformational changes in apo A-1 are then induced, making it more prone to fibril formation. Since some forms of amyloid fibrils are known to be cytotoxic, apo A-1 derived amyloid may contribute to the injury caused by other factors in atherosclerotic lesions.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2000. , 74 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 636
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-28611Local ID: 13766ISBN: 91-7219-737-4 (print)OAI: oai:DiVA.org:liu-28611DiVA: diva2:249422
Public defence
2000-09-15, Berzeliussalen, Hälsouniversitetet, Linköping, 09:00 (Swedish)
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-08-13Bibliographically approved
List of papers
1. Senile aortic amyloid: Evidence for two distinct forms of localized deposits
Open this publication in new window or tab >>Senile aortic amyloid: Evidence for two distinct forms of localized deposits
1992 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 140, no 4, 871-877 p.Article in journal (Refereed) Published
Abstract [en]

Aortic tissues obtained at autopsy were examined from 84 patients (age, 18-96 years). Amyloid deposits were present in the media in 61 of 63 (97%) of the patients above the age of 50. In addition, intimal amyloid deposits were present in 35% of this group. Intimal amyloid differed from medial amyloid both in its morphologic characteristics and its association with atherosclerosis. An antiserum raised to a low molecular weight protein extracted from amyloid fibrils of the aortic media reacted specifically with medial amyloid but did not react with intimal deposits. Neither type of amyloid reacted with anti-ATTR (Senile systemic amyloid), anti-AANF (isolated atrial amyloid), or antisera to other known forms of amyloid. These findings are consistent with the presence of two separate forms of localized amyloid in the aging aorta.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79732 (URN)1562050 (PubMedID)
Available from: 2012-08-13 Created: 2012-08-13 Last updated: 2017-12-07Bibliographically approved
2. Apolipoprotein A1-derived amyloid in human aortic atherosclerotic plaques
Open this publication in new window or tab >>Apolipoprotein A1-derived amyloid in human aortic atherosclerotic plaques
Show others...
1995 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 147, no 5, 1186-1192 p.Article in journal (Refereed) Published
Abstract [en]

Amyloid deposits in the aortic intima are very common in association with atherosclerosis and aging. In the present study, a major fibril protein purified from amyloid present in human atherosclerotic plaques was shown to be a 69-amino acid N-terminal fragment of apolipoprotein AI. Although senile form of localized apolipoprotein AI-derived amyloidosis has recently been documented in pulmonary vessels of dogs, this is the first example of a localized human amyloid derived from this apolipoprotein.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79733 (URN)7485381 (PubMedID)
Available from: 2012-08-13 Created: 2012-08-13 Last updated: 2017-12-07Bibliographically approved
3. Extensive Intimal Apolipoprotein A1-Derived Amyloid Deposits in a Patient with an Apolipoprotein A1 Mutation
Open this publication in new window or tab >>Extensive Intimal Apolipoprotein A1-Derived Amyloid Deposits in a Patient with an Apolipoprotein A1 Mutation
Show others...
1998 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 242, no 3, 534-539 p.Article in journal (Refereed) Published
Abstract [en]

In the aortic intima amyloid deposits are often associated with atherosclerotic plaques. In a recent study of one patient with aortic intimal amyloid the major fibril protein was an N-terminal fragment of apolipoprotein A1 (apoA1) consisting of 69 amino acid residues. In the present study, we have screened the apoA1 gene for mutations in autopsy cases with aortic intimal amyloid immunohistochemically positive for apoA1, using single stranded conformational polymorphism (SSCP) analysis and DNA sequencing. All cases except one had a normal apoA1 gene sequence. One case of exceptionally severe atherosclerosis combined with extensive intimal amyloid deposits showed an apoA1 deletion corresponding to Lys 107. Thus, wild type apoA1 is amyloidogenic but our findings suggest that the expression of a mutant apoA1-form may be associated with enhanced amyloidogenicity.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79734 (URN)10.1006/bbrc.1997.8005 (DOI)
Available from: 2012-08-13 Created: 2012-08-13 Last updated: 2017-12-07Bibliographically approved
4. Apolipoprotein A-1-derived amyloid in atherosclerotic plaques of the human aorta
Open this publication in new window or tab >>Apolipoprotein A-1-derived amyloid in atherosclerotic plaques of the human aorta
2001 (English)In: Journal of Pathology, ISSN 0022-3417, E-ISSN 1096-9896, Vol. 193, no 2, 270-275 p.Article in journal (Refereed) Published
Abstract [en]

Previous studies have shown that the amyloid localized to the aortic intima may be a biochemical entity different from other forms of localized amyloid. The amyloid fibril protein in one patient studied consisted of an N-terminal fragment of apolipoprotein A-1 (apo A-1). Since this patient was later shown to carry a missense mutation in the apo A-1 gene, leading to a deletion at position 107 of the mature protein, the question remained whether wild-type apo A-1 is amyloidogenic. In autopsy specimens from the thoracic aorta from 69 individuals, intimal atherosclerotic plaque-related amyloid was present in 11 cases (16%) and amyloid outside plaques in 37 cases (54%). The immunoreactivity of amyloid localized to the aortic intima was evaluated with the aid of antisera against N-terminal segments of apo A-1. The amyloid in association with atherosclerotic plaques was positively labelled by immunohistochemistry. The amyloid fibril protein from one patient, previously shown not to carry any mutation in the apo A-1 gene, was purified and shown by amino acid sequence analysis to be of apo A-1 nature. The result shows that wild-type apo A-1 is amyloidogenic and gives rise to a common localized form of amyloid associated with atherosclerosis.

Keyword
amyloid, aorta, intima, apolipoprotein A-1, atherosclerosis, immunocytochemistry
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25966 (URN)10.1002/1096-9896(2000)9999:9999<::AID-PATH753>3.0.CO;2-S (DOI)10414 (Local ID)10414 (Archive number)10414 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
5. Apolipoprotein A-I–Derived Amyloid in Atherosclerosis: Its Association With Plasma Levels of Apolipoprotein A-I and Cholesterol
Open this publication in new window or tab >>Apolipoprotein A-I–Derived Amyloid in Atherosclerosis: Its Association With Plasma Levels of Apolipoprotein A-I and Cholesterol
Show others...
2001 (English)In: American Journal of Clinical Pathology, ISSN 0002-9173, E-ISSN 1943-7722, Vol. 115, 298-303 p.Article in journal (Refereed) Published
Abstract [en]

Wild-type apolipoprotein A-I (apo A-I)–derived amyloid commonly occurs in atherosclerotic plaques. To clarify apo A-I amyloid formation, plasma levels of apo A-I and cholesterol were related to the presence of amyloid in atherosclerotic plaques in 15 patients with peripheral atherosclerosis, subjected to arterial reconstruction. Plasma levels of apo A-I and high-density lipoprotein (HDL) cholesterol were slightly higher in patients with apo A-I–derived amyloid than in those without, but the difference was not significant. Levels of low-density lipoprotein cholesterol and total cholesterol were significantly higher in the group with amyloid. High concentrations of apo A-I in the arterial intima are probably of greater importance to amyloid formation than high plasma levels of the protein. During atherosclerosis, the acute phase reactant serum amyloid A may displace apo A-I from HDL, leading to increased concentration of lipid-free apo A-I in the intima and conformational changes of apo A-I, which make it more fibrillogenic. Some forms of amyloid fibrils have been shown to be cytotoxic. Apo AI–derived amyloid is possibly a pathogenically important factor in atherosclerosis.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25965 (URN)10413 (Local ID)10413 (Archive number)10413 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved

Open Access in DiVA

No full text

By organisation
Molecular and Immunological PathologyFaculty of Health Sciences
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 59 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf