Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Editorial
. 2018 Jan;10(1):64-69.
doi: 10.21037/jtd.2017.12.47.

The quest for immunotherapy in atherosclerosis: CANTOS study, interleukin-1β and vascular inflammation

Valmore Bermúdez  1   2 , Joselyn Rojas-Quintero  2   3 , Manuel Velasco  4
Affiliations
Editorial

The quest for immunotherapy in atherosclerosis: CANTOS study, interleukin-1β and vascular inflammation

Valmore Bermúdez et al. J Thorac Dis. 2018 Jan.
No abstract available

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
All roads lead to Rome: vascular inflammation. Multiple pro-inflammatory pathways can participate in triggering and amplifying endothelial dysfunction, offering multiple venues to explore, target wise. IL-1 pathway blockade offers three targets worth exploring: blocking the cytokine (canakinumab), its receptor (anakinra) or IL-1 receptor antagonist therapy. In regards to cholesterol synthesis, besides the obvious hypolipemic effect observed with statins, it can also be argued that they lower geranyl-geranyl-pyrophosphate, and in this, lowering Rac1 activation. Ergo, farnesylation inhibition is also an attractive target for oxidative stress control. As for immunization, conventional and experimental vaccines have been proposed. Rac1 activation it’s common pathway of endothelial inflammation for C. pneumoniae, so a pathogen-specific therapeutic vaccine is viable target. Vaccines against neoantigens such as ApoB100, and specific common epitopes which are conserved even after LDL modification, are underway. Finally, using ApoA1 mimetics is a direct way to accelerate and increase the efficacy of reverse cholesterol transport. IL, interleukin; TNF-α, tumor necrosis factor-α; Rac1, Ras-related C3 botulinum toxin substrate 1; SMC, smooth muscle cell; VLDL, very low-density lipoprotein; HDL, high density lipoprotein; LDL, low density lipoprotein; mLDL, modified low density lipoprotein; ApoB100, apolipoprotein B100; HMG-CoA, hydroxy-methyl-glutaryl coenzyme A; NLRP3, Nod-like receptor family pyrin domain containing 3; NF-κβ, nuclear factor-κβ; JNK, c-Jun N-terminal kinase; p38, p38 mitogen-activated protein kinases.
See this image and copyright information in PMC

Comment on

  • Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.
    Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ; CANTOS Trial Group. Ridker PM, et al. N Engl J Med. 2017 Sep 21;377(12):1119-1131. doi: 10.1056/NEJMoa1707914. Epub 2017 Aug 27. N Engl J Med. 2017. PMID: 28845751 Clinical Trial.

References

    1. Capron L. Pathogenesis of atherosclerosis: an update on the three main theories. Ann Cardiol Angeiol (Paris) 1989;38:631-4. - PubMed
    1. Müller C. Angina pectoris in hereditary xanthomatosis. Arch Intern Med 1939;64:675-700. 10.1001/archinte.1939.00190040016002 - DOI
    1. Wilson PW, Garrison RJ, Castelli WP, et al. Prevalence of coronary heart disease in the Framingham Offspring Study: role of lipoprotein cholesterols. Am J Cardiol 1980;46:649-54. 10.1016/0002-9149(80)90516-0 - DOI - PubMed
    1. Thompson GR, Packard CJ, Stone NJ. Goals of statin therapy: three viewpoints. Curr Atheroscler Rep 2002;4:26-33. 10.1007/s11883-002-0059-6 - DOI - PubMed
    1. Bertrand MJ, Tardif JC. Inflammation and beyond: new directions and emerging drugs for treating atherosclerosis. Expert Opin Emerg Drugs 2017;22:1-26. 10.1080/14728214.2017.1269743 - DOI - PubMed

LinkOut - more resources