PMID- 10411933
OWN - NLM
STAT- MEDLINE
DCOM- 19990823
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 15
DP  - 1999 Jul 20
TI  - Medin: an integral fragment of aortic smooth muscle cell-produced lactadherin
      forms the most common human amyloid.
PG  - 8669-74
AB  - Aortic medial amyloid is a form of localized amyloid that occurs in virtually all
      individuals older than 60 years. The importance and impact of the amyloid
      deposits are unknown. In this study we have purified a 5.5-kDa aortic medial
      amyloid component, by size-exclusion chromatography and RP-HPLC, from three
      individuals, and we have shown by amino acid sequence analysis that the amyloid
      is derived from an integral proteolytic fragment of lactadherin. Lactadherin is a
      364-aa glycoprotein, previously known to be expressed by mammary epithelial cells
      as a cell surface protein and secreted as part of the milk fat globule membrane. 
      The multidomain protein has a C-terminal domain showing homology to blood
      coagulation factors V and VIII. We found that the main constituent of aortic
      medial amyloid is a 50-aa-long peptide, here called medin, that is positioned
      within the coagulation factor-like domain of lactadherin. Our result is supported
      by the specific labeling of aortic medial amyloid in light and electron
      microscopy with two rabbit antisera raised against two synthetic peptides
      corresponding to different parts of medin. By using in situ hybridization we have
      shown that lactadherin is expressed by aortic medial smooth muscle cells.
      Furthermore, one of the synthetic peptides forms amyloid-like fibrils in vitro.
      Lactadherin was not previously known to be an amyloid precursor protein or to be 
      expressed in aortic tissue. The structure of lactadherin may implicate an
      important regulatory function in the aorta.
FAU - Haggqvist, B
AU  - Haggqvist B
AD  - Division of Molecular and Immunological Pathology and Cell Biology, Linkoping
      University, S-581 85 Linkoping, Sweden.
FAU - Naslund, J
AU  - Naslund J
FAU - Sletten, K
AU  - Sletten K
FAU - Westermark, G T
AU  - Westermark GT
FAU - Mucchiano, G
AU  - Mucchiano G
FAU - Tjernberg, L O
AU  - Tjernberg LO
FAU - Nordstedt, C
AU  - Nordstedt C
FAU - Engstrom, U
AU  - Engstrom U
FAU - Westermark, P
AU  - Westermark P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Amyloid)
RN  - 0 (Antibodies)
RN  - 0 (Antigens, Surface)
RN  - 0 (DNA, Complementary)
RN  - 0 (MFGE8 protein, human)
RN  - 0 (Milk Proteins)
RN  - 0 (Muscle Proteins)
RN  - 0 (Peptide Fragments)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Amino Acid Sequence
MH  - Amyloid/*chemistry/ultrastructure
MH  - Antibodies/immunology
MH  - Antigens, Surface/*chemistry
MH  - Aorta/metabolism
MH  - DNA, Complementary/genetics
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Male
MH  - Microscopy, Immunoelectron
MH  - Milk Proteins/*chemistry
MH  - Molecular Sequence Data
MH  - Muscle Proteins/*chemistry/isolation & purification
MH  - Muscle, Smooth, Vascular/*chemistry/metabolism
MH  - Peptide Fragments/chemistry/immunology
MH  - Sequence Analysis
PMC - PMC17574
EDAT- 1999/07/21 00:00
MHDA- 1999/07/21 00:01
CRDT- 1999/07/21 00:00
PHST- 1999/07/21 00:00 [pubmed]
PHST- 1999/07/21 00:01 [medline]
PHST- 1999/07/21 00:00 [entrez]
AID - 10.1073/pnas.96.15.8669 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8669-74. doi:
      10.1073/pnas.96.15.8669.