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NLM CIT. ID: 91067711
TITLE: Immunological evidence for the accumulation of lipoprotein(a) in
the atherosclerotic lesion of the hypoascorbemic guinea pig.
AUTHOR: Rath M; Pauling L
ADDRESS:
Linus Pauling Institute of Science and Medicine, Palo Alto, CA
94306-2025.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGE: Eng
REGISTRY NUMBERS:
0 (Antibodies)
0 (Lipoprotein(a))
0 (Lipoproteins)
ABSTRACT:
Lipoprotein(a) [Lp(a)] is an extremely atherogenic lipoprotein.
Lp(a) has been found in the plasma of humans and other primates,
but until now only in a few other species. The mechanism by which
it exerts its atherogenicity is still poorly understood. We
observed that Lp(a) has been found in the plasma of several
species unable to synthesize ascorbate and not in other species.
We have now detected apoprotein(a) in the plasma of the guinea
pig. We induced atherosclerosis in this animal by dietary
ascorbate depletion and, using SDS/PAGE and subsequent
immunoblotting, we identified Lp(a) as accumulating in the
atherosclerotic plaque. Most importantly, adequate amounts of
ascorbate (40 mg per kg of body weight per day) prevent the
development of atherosclerotic lesions in this animal model and
the accumulation of Lp(a) in the arterial wall. We suggest an
analogous mechanism in humans because of the similarity between
guinea pigs and humans with respect to both the lack of
endogenous ascorbate production and the role of Lp(a) in human
atherosclerosis.
MAIN MESH HEADINGS:
Lipoproteins/ANALYSIS/*METABOLISM
Atherosclerosis/COMPLICATIONS/*METABOLISM/PATHOLOGY
Ascorbic Acid Deficiency/COMPLICATIONS/*METABOLISM
ADDITIONAL MESH SUBJECTS:
Support, Non-U.S. Gov't
Muscle, Smooth, Vascular/METABOLISM/PATHOLOGY
Guinea Pigs
Female
Electrophoresis, Polyacrylamide Gel
Blotting, Western
Aorta/METABOLISM/PATHOLOGY
Antibodies
Animal
SOURCE: Proc Natl Acad Sci U S A 1990 Dec;87(23):9388-90
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NLM CIT. ID: 91031571
TITLE: Lipoprotein(a) in the arterial wall.
AUTHOR: Beisiegel U; Rath M; Reblin T; Wolf K; Niendorf A
ADDRESS:
Medizinische Kernklinik und Poliklinik, Universitatskrankenhaus
Eppendorf, Hamburg, F.R.G.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGE: Eng
REGISTRY NUMBERS:
0 (Apoproteins)
0 (Lipoprotein(a))
0 (Lipoproteins)
0 (Triglycerides)
57-88-5 (Cholesterol)
ABSTRACT:
We compared CHD patients with healthy blood donors to confirm the
role of Lp(a) as an independent risk factor. More important, we
performed biochemical and immunohistochemical studies to evaluate
the potential mechanism by which Lp(a) causes CHD. We measured
the Lp(a) concentration in comparison with other lipoprotein
parameters in fresh human arterial wall biopsies and, in autopsy
tissue, we localized apo (a) and apo B, as well as fibrin, with
immunohistochemical methods in different vessel areas. Density
gradient ultracentrifugation was used to analyse lipoprotein
fractions isolated from human arterial wall. Lp(a) accumulates in
the intima, preferentially in plaque areas, dependent on the
serum Lp(a) level. Most of the Lp(a) can be located
extracellularly, but apo(a) can also be detected in foam cells. A
strong co-localization has been observed for apo(a) and apo B;
only a few areas containing only apo B were detected. Moreover, a
striking co-localization for apo(a) and fibrin was found. The
possibilities for the pathways by which Lp(a) enters the arterial
wall and accumulates extracellularly are discussed on the basis
of the present data and recent data published by other groups.
MAIN MESH HEADINGS:
Lipoproteins/*ANALYSIS
Endothelium, Vascular/*CHEMISTRY
Coronary Disease/*METABOLISM
Aorta/*CHEMISTRY
ADDITIONAL MESH SUBJECTS:
Triglycerides/ANALYSIS
Support, Non-U.S. Gov't
Proteins/ANALYSIS
Middle Age
Lipids/ANALYSIS
Immunohistochemistry
Human
Cholesterol/ANALYSIS
Apoproteins/ANALYSIS
SOURCE: Eur Heart J 1990 Aug;11 Suppl E:174-83
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NLM CIT. ID: 90349583
TITLE: Hypothesis: lipoprotein(a) is a surrogate for ascorbate
[published erratum appears in Proc Natl Acad Sci U S A 1991 Dec
15;88(24):11588]
AUTHOR: Rath M; Pauling L
ADDRESS:
Linus Pauling Institute of Science and Medicine, Palo Alto, CA
94306.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGE: Eng
REGISTRY NUMBERS:
0 (Antioxidants)
0 (Lipoprotein(a))
0 (Lipoproteins)
50-81-7 (Ascorbic Acid)
ABSTRACT:
The concept that lipoprotein(a) [Lp(a)] is a surrogate for
ascorbate is suggested by the fact that this lipoprotein is found
generally in the blood of primates and the guinea pig, which have
lost the ability to synthesize ascorbate, but only rarely in the
blood of other animals. Properties of Lp(a) that are shared with
ascorbate, in accordance with this hypothesis, are the
acceleration of wound healing and other cell-repair mechanisms,
the strengthening of the extracellular matrix (e.g., in blood
vessels), and the prevention of lipid peroxidation. High plasma
Lp(a) is associated with coronary heart disease and other forms
of atherosclerosis in humans, and the incidence of cardiovascular
disease is decreased by elevated ascorbate. Similar observations
have been made in cancer and diabetes. We have formulated the
hypothesis that Lp(a) is a surrogate for ascorbate in humans and
other species and have marshaled the evidence bearing on this
hypothesis.
MAIN MESH HEADINGS:
Lipoproteins/*PHYSIOLOGY
Cardiovascular Diseases/*PHYSIOPATHOLOGY
Ascorbic Acid/*METABOLISM
ADDITIONAL MESH SUBJECTS:
Wound Healing
Neoplasms/PHYSIOPATHOLOGY
Human
Evolution
Disease Models, Animal
Diabetes Mellitus/PHYSIOPATHOLOGY
Atherosclerosis/PHYSIOPATHOLOGY
Antioxidants/METABOLISM
Animal
SOURCE: Proc Natl Acad Sci U S A 1990 Aug;87(16):6204-7
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NLM CIT. ID: 90312898
TITLE: Morphological detection and quantification of lipoprotein(a)
deposition in atheromatous lesions of human aorta and coronary
arteries [published erratum appears in Virchows Arch A Pathol
Anat Histopathol 1991;418(1):86]
AUTHOR: Niendorf A; Dietel M; Beisiegel U; Arps H; Peters S
Wolf K; Rath M
ADDRESS:
Institut fur Pathologie, Universitat Hamburg, Federal Republic
of Germany.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGE: Eng
REGISTRY NUMBERS:
0 (Apolipoproteins A)
0 (Apolipoproteins B)
0 (Lipoprotein(a))
0 (Lipoproteins)
ABSTRACT:
Lipoprotein(a), as an atherogenic particle, represents an
independent risk factor for coronary heart disease. In the
present study the morphological distribution of apoprotein (a)
and apoprotein B within the arterial wall is described.
Apoprotein B, a constituent of very low-density lipoprotein,
low-density lipoprotein and lipoprotein(a) has previously been
demonstrated in atheromatous lesions. Lipoprotein(a) possesses an
additional protein, designated apoprotein (a). Autopsy material
(n = 74) from the left coronary artery and from the thoracic
aorta has been examined by means of immunohistochemistry and both
apoprotein (a) and apoprotein B were detected, primarily
associated with the extracellular matrix and accumulating in
lesions in the arterial wall. The staining pattern for both
antigens was almost always found to be congruent, suggesting that
the detection of (a)-antigen has to be attributed at least in
part to the presence of lipoprotein(a). It is concluded that both
low-density lipoprotein and lipoprotein(a) have an important role
in the pathogenesis of atherosclerosis.
MAIN MESH HEADINGS:
Lipoproteins/*METABOLISM
Coronary Disease/*METABOLISM/PATHOLOGY
Atherosclerosis/*METABOLISM/PATHOLOGY
Arteriosclerosis/*METABOLISM
Aortic Diseases/*METABOLISM/PATHOLOGY
ADDITIONAL MESH SUBJECTS:
Tissue Distribution
Middle Age
Infant, Newborn
Infant
Immunohistochemistry
Human
Coronary Vessels/METABOLISM/PATHOLOGY
Comparative Study
Child, Preschool
Child
Apolipoproteins B/METABOLISM
Apolipoproteins A/METABOLISM
Aorta/METABOLISM/PATHOLOGY
Aged, 80 and over
Aged
Adult
Adolescence
SOURCE: Virchows Arch A Pathol Anat Histopathol 1990;417(2):105-11