Angela Pirillo1,2, Fabrizia Bonacina3, Giuseppe Danilo Norata3,4, Alberico Luigi Catapano5,6,7. 1. Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Milan, Italy. 2. IRCCS Multimedica, Milan, Italy. 3. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy. 4. School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia. 5. IRCCS Multimedica, Milan, Italy. alberico.catapano@unimi.it. 6. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy. alberico.catapano@unimi.it. 7. Department of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica, Via Balzaretti, 9, 20133, Milan, Italy. alberico.catapano@unimi.it.
Abstract
PURPOSE OF REVIEW: Atherosclerosis is an inflammatory disorder of the arterial wall, in which several players contribute to the onset and progression of the disease. Besides the well-established role of lipids, specifically cholesterol, and immune cell activation, new insights on the molecular mechanisms underlying the atherogenic process have emerged. RECENT FINDINGS: Meta-inflammation, a condition of low-grade immune response caused by metabolic dysregulation, immunological memory of innate immune cells (referred to as "trained immunity"), cholesterol homeostasis in dendritic cells, and immunometabolism, i.e., the interplay between immunological and metabolic processes, have all emerged as new actors during atherogenesis. These observations reinforced the interest in directly targeting inflammation to reduce cardiovascular disease. The novel acquisitions in pathophysiology of atherosclerosis reinforce the tight link between lipids, inflammation, and immune response, and support the benefit of targeting LDL-C as well as inflammation to decrease the CVD burden. How this will translate into the clinic will depend on the balance between costs (monoclonal antibodies either to PCSK9 or to IL-1ß), side effects (increased incidence of death due to infections for anti-IL-1ß antibody), and the benefits for patients at high CVD risk.
PURPOSE OF REVIEW: Atherosclerosis is an inflammatory disorder of the arterial wall, in which several players contribute to the onset and progression of the disease. Besides the well-established role of lipids, specifically cholesterol, and immune cell activation, new insights on the molecular mechanisms underlying the atherogenic process have emerged. RECENT FINDINGS:Meta-inflammation, a condition of low-grade immune response caused by metabolic dysregulation, immunological memory of innate immune cells (referred to as "trained immunity"), cholesterol homeostasis in dendritic cells, and immunometabolism, i.e., the interplay between immunological and metabolic processes, have all emerged as new actors during atherogenesis. These observations reinforced the interest in directly targeting inflammation to reduce cardiovascular disease. The novel acquisitions in pathophysiology of atherosclerosis reinforce the tight link between lipids, inflammation, and immune response, and support the benefit of targeting LDL-C as well as inflammation to decrease the CVD burden. How this will translate into the clinic will depend on the balance between costs (monoclonal antibodies either to PCSK9 or to IL-1ß), side effects (increased incidence of death due to infections for anti-IL-1ß antibody), and the benefits for patients at high CVD risk.
Authors: Giuseppe Danilo Norata; Giuseppina Caligiuri; Triantafyllos Chavakis; Giuseppe Matarese; Mihai Gheorge Netea; Antonino Nicoletti; Luke A J O'Neill; Federica M Marelli-Berg Journal: Immunity Date: 2015-09-15 Impact factor: 31.745
Authors: Andrew J Murphy; Mani Akhtari; Sonia Tolani; Tamara Pagler; Nora Bijl; Chao-Ling Kuo; Mi Wang; Marie Sanson; Sandra Abramowicz; Carrie Welch; Andrea E Bochem; Jan Albert Kuivenhoven; Laurent Yvan-Charvet; Alan R Tall Journal: J Clin Invest Date: 2011-10 Impact factor: 14.808
Authors: R de Nooijer; J H von der Thüsen; C J N Verkleij; J Kuiper; J W Jukema; E E van der Wall; J C van Berkel; E A L Biessen Journal: Arterioscler Thromb Vasc Biol Date: 2004-10-07 Impact factor: 8.311
Authors: Liudmila V Dergunova; Elena V Nosova; Veronika G Dmitrieva; Alexandra V Rozhkova; Ekaterina V Bazaeva; Svetlana A Limborska; Alexander D Dergunov Journal: J Med Biochem Date: 2020-09-02 Impact factor: 3.402
Authors: Julita Anna Krahel; Anna Baran; Tomasz W Kamiński; Magdalena Maciaszek; Iwona Flisiak Journal: J Clin Med Date: 2020-03-26 Impact factor: 4.241