Medin aggregation causes cerebrovascular dysfunction in aging wild-type mice
Standard
Medin aggregation causes cerebrovascular dysfunction in aging wild-type mice. / Degenhardt, Karoline; Wagner, Jessica; Skodras, Angelos; Candlish, Michael; Koppelmann, Anna Julia; Wild, Katleen; Maxwell, Rusheka; Rotermund, Carola; von Zweydorf, Felix; Gloeckner, Christian Johannes; Davies, Hannah A; Madine, Jillian; Del Turco, Domenico; Feederle, Regina; Lashley, Tammaryn; Deller, Thomas; Kahle, Philipp; Hefendehl, Jasmin K; Jucker, Mathias; Neher, Jonas J.
In: P NATL ACAD SCI USA, Vol. 117, No. 38, 22.09.2020, p. 23925-23931.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Medin aggregation causes cerebrovascular dysfunction in aging wild-type mice
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 J
PY - 2020/9/22
Y1 - 2020/9/22
N2 - 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.
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 - Animals
KW - Antigens, Surface/genetics
KW - Aorta/metabolism
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 - Vascular Diseases/metabolism
U2 - 10.1073/pnas.2011133117
DO - 10.1073/pnas.2011133117
M3 - SCORING: Journal article
C2 - 32900929
VL - 117
SP - 23925
EP - 23931
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 38
ER -