TY  - JOUR
AU  - Degenhardt, Karoline
AU  - Wagner, Jessica
AU  - Skodras, Angelos
AU  - Candlish, Michael
AU  - Koppelmann, Anna Julia
AU  - Wild, Katleen
AU  - Maxwell, Rusheka
AU  - Rotermund, Carola
AU  - von Zweydorf, Felix
AU  - Gloeckner, Christian Johannes
AU  - Davies, Hannah A
AU  - Madine, Jillian
AU  - Del Turco, Domenico
AU  - Feederle, Regina
AU  - Lashley, Tammaryn
AU  - Deller, Thomas
AU  - Kahle, Philipp
AU  - Hefendehl, Jasmin K
AU  - Jucker, Mathias
AU  - Neher, Jonas
TI  - Medin aggregation causes cerebrovascular dysfunction in aging wild-type mice.
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 117
IS  - 38
SN  - 1091-6490
CY  - Washington, DC
PB  - National Acad. of Sciences
M1  - DZNE-2021-00215
SP  - 23925 - 23931
PY  - 2020
N1  - ISSN 1091-6490 not unique: **3 hits**.
AB  - Medin is the most common amyloid known in humans, as it can be found in blood vessels of the upper body in virtually everybody over 50 years of age. However, it remains unknown whether deposition of Medin plays a causal role in age-related vascular dysfunction. We now report that aggregates of Medin also develop in the aorta and brain vasculature of wild-type mice in an age-dependent manner. Strikingly, genetic deficiency of the Medin precursor protein, MFG-E8, eliminates not only vascular aggregates but also prevents age-associated decline of cerebrovascular function in mice. Given the prevalence of Medin aggregates in the general population and its role in vascular dysfunction with aging, targeting Medin may become a novel approach to sustain healthy aging.
KW  - Aged, 80 and over
KW  - Aging: metabolism
KW  - Amyloid: genetics
KW  - Amyloid: metabolism
KW  - Animals
KW  - Antigens, Surface: genetics
KW  - Antigens, Surface: metabolism
KW  - Aorta: metabolism
KW  - Aorta: pathology
KW  - Brain Chemistry: physiology
KW  - Cerebrovascular Circulation: physiology
KW  - Female
KW  - Humans
KW  - Male
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Milk Proteins: genetics
KW  - Milk Proteins: metabolism
KW  - Vascular Diseases: metabolism
KW  - Vascular Diseases: pathology
KW  - MFG-E8 (Other)
KW  - Medin (Other)
KW  - aging (Other)
KW  - amyloid (Other)
KW  - cerebrovascular dysfunction (Other)
KW  - Amyloid (NLM Chemicals)
KW  - Antigens, Surface (NLM Chemicals)
KW  - MFGE8 protein, human (NLM Chemicals)
KW  - Mfge8 protein, mouse (NLM Chemicals)
KW  - Milk Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:32900929
C2  - pmc:PMC7519322
DO  - DOI:10.1073/pnas.2011133117
UR  - https://pub.dzne.de/record/154362
ER  -