Protective role of chaperone-mediated autophagy against atherosclerosis-Reference-Cited by-同舟云学术

Protective role of chaperone-mediated autophagy against atherosclerosis

Published:2022-04 Issue:14 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Madrigal-Matute Julio¹²,de Bruijn Jenny³,van Kuijk Kim³⁴,Riascos-Bernal Dario F.⁵,Diaz Antonio¹²,Tasset Inmaculada¹²,Martín-Segura Adrián¹²,Gijbels Marion J. J.³⁶⁷,Sander Bianca³,Kaushik Susmita¹²,Biessen Erik A. L.³⁸,Tiano Simoni¹²,Bourdenx Mathieu¹²,Krause Gregory J.¹²,McCracken Ian⁹,Baker Andrew H.³⁹^ORCID,Jin Han³^ORCID,Sibinga Nicholas E. S.¹⁵,Bravo-Cordero Jose Javier¹⁰,Macian Fernando²¹¹,Singh Rajat¹²⁵^ORCID,Rensen Patrick C. N.¹²¹³^ORCID,Berbée Jimmy F. P.¹²¹³,Pasterkamp Gerard¹⁴,Sluimer Judith C.³⁹,Cuervo Ana Maria¹²⁵^ORCID

Affiliation:

1. Department of Development and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461

2. Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 10461

3. Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands

4. Institute of Experimental Medicine and Systems Biology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany

5. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461

6. School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands

7. Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam University Medical Centers, University of Amsterdam, 1081 HV Amsterdam, The Netherlands

8. Institute for Molecular Cardiovascular Research, RWTH Aachen University, 52074 Aachen, Germany

9. Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom

10. Division of Hematology and Medical Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029

11. Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461

12. Section of Endocrinology, Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

13. Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

14. Experimental Cardiology Laboratory, Department of Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands

Abstract

Significance Cardiovascular diseases remain the leading cause of death worldwide, with atherosclerosis being the most common source of clinical events. Metabolic changes with aging associate with concurrent increased risk of both type 2 diabetes and cardiovascular disease, with the former further raising the risk of the latter. The activity of a selective type of autophagy, chaperone-mediated autophagy (CMA), decreases with age or upon dietary excesses. Here we study whether reduced CMA activity increases risk of atherosclerosis in mouse models. We have identified that CMA is up-regulated early in response to proatherogenic challenges and demonstrate that reduced systemic CMA aggravates vascular pathology in these conditions. We also provide proof-of-concept support that CMA up-regulation is an effective intervention to reduce atherosclerosis severity and progression.

Funder

HHS | NIH | National Institute on Aging

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

Fondation Leducq

Hartstichting

American Heart Association

Ramon Areces

HHS | NIH | National Institute of General Medical Sciences

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary