Medin aggregation causes cerebrovascular dysfunction in aging wild-type mice

被引：28

作者：

Degenhardt, Karoline ^{[1
,2
,3
]}

Wagner, Jessica ^{[1
,2
,3
]}

Skodras, Angelos ^{[1
,2
]}

Candlish, Michael ^{[4
,5
]}

Koppelmann, Anna Julia ^{[2
,3
]}

Wild, Katleen ^{[1
]}

Maxwell, Rusheka ^{[2
,6
]}

Rotermund, Carola ^{[1
,6
]}

von Zweydorf, Felix ^{[1
]}

Gloeckner, Christian Johannes ^{[1
,7
]}

Davies, Hannah A. ^{[8
,9
]}

Madine, Jillian ^{[8
,10
]}

Del Turco, Domenico ^{[11
]}

Feederle, Regina ^{[12
,13
]}

Lashley, Tammaryn ^{[14
,15
]}

Deller, Thomas ^{[11
]}

Kahle, Philipp ^{[1
,6
]}

Hefendehl, Jasmin K. ^{[4
,5
]}

Jucker, Mathias ^{[1
,2
]}

Neher, Jonas J. ^{[1
,2
]}

机构：

[1] German Ctr Neurodegenerat Dis DZNE, D-72076 Tubingen, Germany

[2] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Cellular Neurol, D-72072 Tubingen, Germany

[3] Univ Tubingen, Grad Sch Cellular & Mol Neurosci, D-72074 Tubingen, Germany

[4] Goethe Univ Frankfurt, Buchmann Inst Mol Life Sci, D-60438 Frankfurt, Germany

[5] Goethe Univ Frankfurt, Inst Cell Biol & Neurosci, D-60438 Frankfurt, Germany

[6] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat, Lab Funct Neurogenet, D-72076 Tubingen, Germany

[7] Univ Tubingen, Inst Ophthalm Res, Core Facil Med Bioanalyt, Ctr Ophthalmol, D-72076 Tubingen, Germany

[8] Univ Liverpool, Inst Life Course & Med Sci, Dept Cardiovasc & Metab Med, Liverpool L69 3BX, Merseyside, England

[9] Univ Liverpool, Liverpool Ctr Cardiovasc Sci, Liverpool L14 3PE, Merseyside, England

[10] Univ Liverpool, Inst Syst Mol & Integrat Biol, Dept Biochem & Syst Biol, Liverpool L69 7ZB, Merseyside, England

[11] Goethe Univ, Neurosci Ctr, Inst Clin Neuroanat, Dr Senckenberg Anat, D-60590 Frankfurt, Germany

[12] Helmholtz Zentrum Munchen, Inst Diabet & Obes, Res Ctr Environm Hlth, Monoclonal Antibody Core Facil, D-85764 Neuherberg, Germany

[13] DZNE, D-81377 Munich, Germany

[14] UCL, Queen Sq Inst Neurol, Queen Sq Brain Bank Neurol Disorders, London WC1N 1PJ, England

[15] UCL, Queen Sq Inst Neurol, Dept Neurodegenerat Dis, London WC1N 1PJ, England

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2020年 / 117卷 / 38期

关键词：

Medin; MFG-E8; cerebrovascular dysfunction; aging; amyloid; SMOOTH-MUSCLE-CELLS; MOUSE MODEL; A-BETA; BLOOD-FLOW; AMYLOIDOSIS; GROWTH; MFG-E8; VASCULATURE; DEMENTIA; INTEGRIN;

D O I：

10.1073/pnas.2011133117

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：23925 / 23931

页数：7

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