Abstract

Inflammation crucially drives atherosclerosis from disease initiation to the emergence of clinical complications. Targeting pivotal inflammatory pathways without compromising the host defense could compliment therapy with lipid-lowering agents, anti-hypertensive treatment, and lifestyle interventions to address the substantial residual cardiovascular risk that remains beyond classical risk factor control. Detailed understanding of the intricate immune mechanisms that propel plaque instability and disruption is indispensable for the development of novel therapeutic concepts. In this review, we provide an overview on the role of key immune cells in plaque inception and progression, and discuss recently identified maladaptive immune phenomena that contribute to plaque destabilization, including epigenetically programmed trained immunity in myeloid cells, pathogenic conversion of autoreactive regulatory T-cells and expansion of altered leukocytes due to clonal hematopoiesis. From a more global perspective, the article discusses how systemic crises such as acute mental stress or infection abruptly raise plaque vulnerability and summarizes recent advances in understanding the increased cardiovascular risk associated with COVID-19 disease. Stepping outside the box, we highlight the role of gut dysbiosis in atherosclerosis progression and plaque vulnerability. The emerging differential role of the immune system in plaque rupture and plaque erosion as well as the limitations of animal models in studying plaque disruption are reviewed.

Highlights

  • Inflammation crucially drives atherosclerosis from disease initiation to the emergence of clinical complications

  • We provide an overview on the role of key immune cells in plaque inception and progression, and discuss recently identified maladaptive immune phenomena that contribute to plaque destabilization, including epigenetically programmed trained immunity in myeloid cells, pathogenic conversion of autoreactive regulatory T-cells and expansion of altered leukocytes due to clonal hematopoiesis

  • Does the training effect and duration vary between the different innate immune cell types? Does it directly influence the players of the adaptive immune system that are omnipresent in the plaque? Is trained immunity thoroughly reversible and can we therapeutically exploit this? Could some of the “genetic” cardiovascular risk be due to training-induced epigenetic alterations being passed on in the germline?

Read more

Summary

Immune Mechanisms of Plaque Instability

Teresa Gerhardt , 1,2,3 Arash Haghikia , 1,2,3 Philip Stapmanns 1 and David Manuel Leistner * 1,2,3. Detailed understanding of the intricate immune mechanisms that propel plaque instability and disruption is indispensable for the development of novel therapeutic concepts. We provide an overview on the role of key immune cells in plaque inception and progression, and discuss recently identified maladaptive immune phenomena that contribute to plaque destabilization, including epigenetically programmed trained immunity in myeloid cells, pathogenic conversion of autoreactive regulatory T-cells and expansion of altered leukocytes due to clonal hematopoiesis. From a more global perspective, the article discusses how systemic crises such as acute mental stress or infection abruptly raise plaque vulnerability and summarizes recent advances in understanding the increased cardiovascular risk associated with COVID-19 disease. We highlight the role of gut dysbiosis in atherosclerosis progression and plaque vulnerability. The emerging differential role of the immune system in plaque rupture and plaque erosion as well as the limitations of animal models in studying plaque disruption are reviewed

CLINICAL RELEVANCE
ATHEROSCLEROTIC PLAQUE FORMATION AND FEATURES OF PLAQUE INSTABILITY
MOUSE MODELS OF PLAQUE
IMMUNE CELLS CRUCIALLY DRIVE
Macrophages and Neutrophils
THAT DESTABILIZE THE PLAQUE
Trained Immunity
Protective Autoimmune Cells
Clonal Hematopoiesis
Immune Mechanisms of Plaque Rupture
Immune Mechanisms of Plaque Erosion
PLAQUES INTO CRISIS
Acute Infections and Cardiovascular
Prevalent Modifiable Risk Factor
Fatty Acids
CONCLUSION
Findings
AUTHOR CONTRIBUTIONS

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.