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Hsp60 in Atherosclerosis: Past, Present and Future

  • Bojana JakicEmail author
  • Georg Wick
  • Giuseppe Cappellano
Chapter
Part of the Heat Shock Proteins book series (HESP, volume 18)

Abstract

Atherosclerosis is a multifactorial inflammatory disease of the arteries that manifests itself with calcified plaque formation within endothelial cells and the smooth muscle cell layer of vessels. T cells that recognize endogenous Hsp60 on endothelial cells initiate the disease. Here, we first describe the initial experiments that led to the discovery of Hsp60 as an autoantigenic driver of atherosclerosis. Then, we address numerous epidemiological and experimental studies performed by our lab and others that have firmly established Hsp60 as an autoantigen. In addition, we describe the pathogenic mechanisms mediated by Hsp60 and list known inducers of ectopic Hsp60 expression. Finally, we discuss the potential of Hsp60-based vaccination against atherosclerosis.

Keywords

Atherosclerosis Autoimmunity Hsp60 Immunoregulation T cell Vaccination 

Abbreviations

AA

Adjuvant arthritis

ApoE

Apolipoprotein E

ARFY

Atherosclerosis risk factor in female youngsters

ARMY

Atherosclerosis risk factor in male youngsters

CAD

Coronary artery disease

CFA

Complete Freund’s adjuvant

cHsp60

Chlamydia pneumoniae-derived Hsp60

CMV

Cytomegalovirus

CRP

C-reactive protein

DC

Dendritic cell(s)

EC

Endothelial cell(s)

ELISA

Enzyme-linked immunosorbent assay

eNOS

Endothelial nitric oxide synthase 3

ERK

Extracellular signal-regulated kinase

HCAEC

Human coronary artery endothelial cell(s)

hHsp60

Human Hsp60

HNE

4-hydroxy-2-nonenal

Hsp

Heat shock protein

Hsp60

Heat shock protein 60

HUVEC

Human umbilical vein endothelial cell(s)

i.p.

Intraperitoneal

i.v.

Intravenous

ICAM-1

Intercellular adhesion molecule 1

IFA

Incomplete Freund’s adjuvant

IFN-γ

Interferon γ

IL

Interleukin

LDL

Low-density lipoprotein

LOX-1

Lectin-like oxidized LDL receptor

LPS

Lipopolysaccharide

MALT

Muscosa-associated lymphoid tissue

MAPK

Mitogen-activated protein kinase

mbHsp60

Mycobacterial Hsp60

MDSCs

Myeloid-derived suppressor cells

MHC

Major histocompatibility complex

MLN

Mesenteric lymph node

NZW

New Zealand white rabbits

OVA

Ovalbumin

oxLDL

Oxidized LDL

RA

Rheumatoid arthritis

s.c.

Subcutaneous

sHsp60

Soluble/circulating Hsp60

TGF-β

Transforming growth factor β

Th

T-helper cells

TLR

Toll-like receptor

TNF-α

Tumor necrosis factor α

Treg

Regulatory T cell

VALT

Vascular-associated lymphoid tissue

VCAM-1

Vascular cell adhesion molecule 1

VSMC

Vascular smooth muscle cell(s)

Notes

Acknowledgments

We would like to thank past and present members of the Laboratory of Autoimmunity for their contributions to the work on Hsp60. We would also like to thank funding agencies that have supported our research; FP-7HEALTH EU funded TOLERAGE, Austrian Science Fund (FWF), Tyrolean Science Fund (Tiroler Wissenschaft Fonds, TWF), the Jubiläumsfonds of the Austrian National Bank (Österreichische National- bank, ÖNB) and the Lore and Udo Saldow Donation. Lastly, we would like to thank Rajam Csordas for critical evaluation of the English language.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Bojana Jakic
    • 1
    • 2
    Email author
  • Georg Wick
    • 1
  • Giuseppe Cappellano
    • 1
    • 3
  1. 1.Laboratory of Autoimmunity, Division of Experimental Pathophysiology and Immunology, BiocenterMedical University of InnsbruckInnsbruckAustria
  2. 2.Division of Translational Cell Genetics, Department for Pharmacology and GeneticsMedical University of InnsbruckInnsbruckAustria
  3. 3.Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Department of Health SciencesUniversity of Piemonte Orientale (UPO)NovaraItaly

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