Immunotherapy for atherosclerosis

Physiological Reviews, vol. 105, pp. 2141–2230

Abstract

Cardiovascular disease is the global number one cause of mortality and morbidity. The majority of cardiovascular diseases are caused by atherosclerosis, a lipid-driven, inflammatory disease of the middle- and large-sized arteries. The disease is characterized by the formation of atherosclerotic plaques throughout the arterial tree. Over the years, insights into the pathogenesis of atherosclerosis have shifted from a "lipid-driven" model to a "response-to-injury" perspective and more recently to a "lipid-driven inflammatory disease" viewpoint. We are now aware that a network of multiple immune cell types and subsets of the innate and adaptive immune system inhabit our arteries. Intricate interactions between these immune cell subsets, nonimmune cells, and local environmental substances such as lipids, cell debris, and calcium cause a fluidic balance of proinflammatory and regulatory responses. A dysregulation of this balance toward a proinflammatory milieu drives atherosclerotic disease progression. Although we have acknowledged that atherosclerosis is an inflammatory disease, state-of-the-art treatments are still based on lipid-lowering, antihypertensive, and lifestyle-changing strategies. In the past decade, clinical phase I, II, and III trials targeting the immune system revealed that patients tolerate immunotherapy, show decreased inflammation, and/or have a reduction in cardiovascular endpoints. However, the search for novel immunotherapeutic targets and treatment regimens as well as stratification of patients who would benefit from such treatments to combat atherosclerotic cardiovascular disease is only just beginning. In this review article, we will highlight the newest insights on the different cell subsets and components of the immune system in atherosclerosis and elaborate on current and future immunotherapeutics to treat atherosclerotic cardiovascular disease.

Authors 8

1. Claudia Gianini Monaco

   University of Oxford

   Affiliation as printed

   OX3 7FY University of Oxford

2. Coleen A. McNamara

   University of Virginia

   Affiliation as printed

   University of Virginia

3. Bram Slütter Aachen

   Leiden University

   Affiliation as printed

   Leiden University

4. Amanda C. Foks Aachen

   Leiden University

   Affiliation as printed

   Leiden University

5. Stefan Bekiranov

   University of Virginia

   Affiliation as printed

   University of Virginia

6. Willem J. M. Mulder

   Radboud University Medical Center · Eindhoven University of Technology

   Affiliation as printed

   Eindhoven University of Technology

   Radboud University Medical Center

7. Isabel Gonçalves

   Lund University

   Affiliation as printed

   Lund University

8. Esther Lutgens corresponding

   Mayo Clinic

   Affiliation as printed

   Mayo Clinic