PMID- 35363568
OWN - NLM
STAT- MEDLINE
DCOM- 20220415
LR  - 20240214
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 119
IP  - 14
DP  - 2022 Apr 5
TI  - Protective role of chaperone-mediated autophagy against atherosclerosis.
PG  - e2121133119
LID - 10.1073/pnas.2121133119 [doi]
LID - e2121133119
AB  - Chaperone-mediated autophagy (CMA) contributes to regulation of energy 
      homeostasis by timely degradation of enzymes involved in glucose and lipid 
      metabolism. Here, we report reduced CMA activity in vascular smooth muscle cells 
      and macrophages in murine and human arteries in response to atherosclerotic 
      challenges. We show that in vivo genetic blockage of CMA worsens atherosclerotic 
      pathology through both systemic and cell-autonomous changes in vascular smooth 
      muscle cells and macrophages, the two main cell types involved in atherogenesis. 
      CMA deficiency promotes dedifferentiation of vascular smooth muscle cells and a 
      proinflammatory state in macrophages. Conversely, a genetic mouse model with 
      up-regulated CMA shows lower vulnerability to proatherosclerotic challenges. We 
      propose that CMA could be an attractive therapeutic target against cardiovascular 
      diseases.
FAU - Madrigal-Matute, Julio
AU  - Madrigal-Matute J
AD  - Department of Development and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY 10461.
AD  - Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 
      10461.
FAU - de Bruijn, Jenny
AU  - de Bruijn J
AD  - Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht 
      University Medical Center, 6229 HX Maastricht, The Netherlands.
FAU - van Kuijk, Kim
AU  - van Kuijk K
AD  - Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht 
      University Medical Center, 6229 HX Maastricht, The Netherlands.
AD  - Institute of Experimental Medicine and Systems Biology, Faculty of Medicine, RWTH 
      Aachen University, 52074 Aachen, Germany.
FAU - Riascos-Bernal, Dario F
AU  - Riascos-Bernal DF
AD  - Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
FAU - Diaz, Antonio
AU  - Diaz A
AD  - Department of Development and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY 10461.
AD  - Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 
      10461.
FAU - Tasset, Inmaculada
AU  - Tasset I
AD  - Department of Development and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY 10461.
AD  - Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 
      10461.
FAU - Martin-Segura, Adrian
AU  - Martin-Segura A
AD  - Department of Development and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY 10461.
AD  - Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 
      10461.
FAU - Gijbels, Marion J J
AU  - Gijbels MJJ
AD  - Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht 
      University Medical Center, 6229 HX Maastricht, The Netherlands.
AD  - School for Oncology and Developmental Biology (GROW), Maastricht University 
      Medical Center, 6229 HX Maastricht, The Netherlands.
AD  - Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam 
      University Medical Centers, University of Amsterdam, 1081 HV Amsterdam, The 
      Netherlands.
FAU - Sander, Bianca
AU  - Sander B
AD  - Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht 
      University Medical Center, 6229 HX Maastricht, The Netherlands.
FAU - Kaushik, Susmita
AU  - Kaushik S
AD  - Department of Development and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY 10461.
AD  - Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 
      10461.
FAU - Biessen, Erik A L
AU  - Biessen EAL
AD  - Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht 
      University Medical Center, 6229 HX Maastricht, The Netherlands.
AD  - Institute for Molecular Cardiovascular Research, RWTH Aachen University, 52074 
      Aachen, Germany.
FAU - Tiano, Simoni
AU  - Tiano S
AD  - Department of Development and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY 10461.
AD  - Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 
      10461.
FAU - Bourdenx, Mathieu
AU  - Bourdenx M
AD  - Department of Development and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY 10461.
AD  - Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 
      10461.
FAU - Krause, Gregory J
AU  - Krause GJ
AD  - Department of Development and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY 10461.
AD  - Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 
      10461.
FAU - McCracken, Ian
AU  - McCracken I
AD  - Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, 
      United Kingdom.
FAU - Baker, Andrew H
AU  - Baker AH
AUID- ORCID: 0000-0003-1441-5576
AD  - Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht 
      University Medical Center, 6229 HX Maastricht, The Netherlands.
AD  - Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, 
      United Kingdom.
FAU - Jin, Han
AU  - Jin H
AUID- ORCID: 0000-0002-0955-6289
AD  - Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht 
      University Medical Center, 6229 HX Maastricht, The Netherlands.
FAU - Sibinga, Nicholas E S
AU  - Sibinga NES
AD  - Department of Development and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY 10461.
AD  - Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
FAU - Bravo-Cordero, Jose Javier
AU  - Bravo-Cordero JJ
AD  - Division of Hematology and Medical Oncology, Department of Medicine, Icahn School 
      of Medicine at Mount Sinai, New York, NY 10029.
FAU - Macian, Fernando
AU  - Macian F
AD  - Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 
      10461.
AD  - Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.
FAU - Singh, Rajat
AU  - Singh R
AUID- ORCID: 0000-0001-9389-8574
AD  - Department of Development and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY 10461.
AD  - Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 
      10461.
AD  - Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
FAU - Rensen, Patrick C N
AU  - Rensen PCN
AUID- ORCID: 0000-0002-8455-4988
AD  - Section of Endocrinology, Department of Internal Medicine, Leiden University 
      Medical Center, 2333 ZA Leiden, The Netherlands.
AD  - Einthoven Laboratory for Experimental Vascular Medicine, Leiden University 
      Medical Center, 2333 ZA Leiden, The Netherlands.
FAU - Berbee, Jimmy F P
AU  - Berbee JFP
AD  - Section of Endocrinology, Department of Internal Medicine, Leiden University 
      Medical Center, 2333 ZA Leiden, The Netherlands.
AD  - Einthoven Laboratory for Experimental Vascular Medicine, Leiden University 
      Medical Center, 2333 ZA Leiden, The Netherlands.
FAU - Pasterkamp, Gerard
AU  - Pasterkamp G
AD  - Experimental Cardiology Laboratory, Department of Cardiology, University Medical 
      Center Utrecht, 3584 CX Utrecht, The Netherlands.
FAU - Sluimer, Judith C
AU  - Sluimer JC
AD  - Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht 
      University Medical Center, 6229 HX Maastricht, The Netherlands.
AD  - Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, 
      United Kingdom.
FAU - Cuervo, Ana Maria
AU  - Cuervo AM
AUID- ORCID: 0000-0002-0771-700X
AD  - Department of Development and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY 10461.
AD  - Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 
      10461.
AD  - Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
LA  - eng
GR  - R01 AG021904/AG/NIA NIH HHS/United States
GR  - RG/20/5/34796/BHF_/British Heart Foundation/United Kingdom
GR  - T32 GM007491/GM/NIGMS NIH HHS/United States
GR  - R01 AI113919/AI/NIAID NIH HHS/United States
GR  - R01 HL149921/HL/NHLBI NIH HHS/United States
GR  - CH/11/2/28733/BHF_/British Heart Foundation/United Kingdom
GR  - P01 AG031782/AG/NIA NIH HHS/United States
GR  - R37 AG021904/AG/NIA NIH HHS/United States
GR  - R01 DK098408/DK/NIDDK NIH HHS/United States
GR  - T32 GM007288/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20220401
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
SB  - IM
CIN - Autophagy. 2022 Oct;18(10):2505-2507. PMID: 35787098
MH  - Animals
MH  - *Atherosclerosis/genetics/pathology
MH  - *Chaperone-Mediated Autophagy/genetics
MH  - Disease Models, Animal
MH  - Lysosomes/metabolism
MH  - Mice
PMC - PMC9168839
OTO - NOTNLM
OT  - atherosclerotic plaques
OT  - lipid challenge
OT  - lysosomes
OT  - proteolysis
OT  - vascular disease
COIS- Competing interest statement: J.M.-M. is a founder and consultant for Instituto 
      Ibions SLP. A.H.B. is a coauthor with T.F. of a review article in 2019. A.M.C. is 
      a cofounder and scientific advisor for the autophagy program at Life Biosciences 
      and consults for Generian Pharmaceuticals and Cognition Therapeutics.
EDAT- 2022/04/02 06:00
MHDA- 2022/04/16 06:00
PMCR- 2022/04/01
CRDT- 2022/04/01 17:13
PHST- 2022/04/01 17:13 [entrez]
PHST- 2022/04/02 06:00 [pubmed]
PHST- 2022/04/16 06:00 [medline]
PHST- 2022/04/01 00:00 [pmc-release]
AID - 202121133 [pii]
AID - 10.1073/pnas.2121133119 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2022 Apr 5;119(14):e2121133119. doi: 
      10.1073/pnas.2121133119. Epub 2022 Apr 1.