Journal Article

Requirement of JNK2 for Scavenger Receptor A: Mediated Foam Cell Formation in Atherogenesis

Eriksson, Urs, Lüscher, Thomas F., Ricci, Romeo, Sumara, Izabela, Borén, Jan, Becher, Burkhard, Eberli, Franz R., Chen, Mian, Moore, Kathryn J., Matter, Christian M., Wagner, Erwin F., Hersberger, Martin, Akhmedov, Alexander, Freeman, Mason W., Kurrer, Michael, Sumara, Grzegorz, Rozenberg, Izabela, Cybulsky, Myron I.

2004

Overview

In vitro studies suggest a role for c-Jun N-terminal kinases (JNKs) in proatherogenic cellular processes. We show that atherosclerosis-prone ApoE-/-mice simultaneously lacking JNK2 ($ApoE^{-/-} JNK2^{-/-}$mice), but not ApoE-/- $JNK1^{-/-}$mice, developed less atherosclerosis than do ApoE-/-mice. Pharmacological inhibition of JNK activity efficiently reduced plaque formation. Macrophages lacking JNK2 displayed suppressed foam cell formation caused by defective uptake and degradation of modified lipoproteins and showed increased amounts of the modified lipoprotein-binding and -internalizing scavenger receptor A (SR-A), whose phosphorylation was markedly decreased. Macrophage-restricted deletion of JNK2 was sufficient to decrease atherogenesis. Thus, JNK2-dependent phosphorylation of SR-A promotes uptake of lipids in macrophages, thereby regulating foam cell formation, a critical step in atherogenesis.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science,American Association for the Advancement of Science (AAAS)
• Subject: Animals / Antigens / Aorta / Aorta - chemistry / Aorta - pathology / Aorta/chemistry/pathology / Apolipoproteins E - genetics / Arteriosclerosis - metabolism / Arteriosclerosis - pathology / Arteriosclerosis/metabolism/pathology / Atherogenic / Atherosclerosis / Atherosclerosis (general aspects, experimental research) / Biochemistry / Biological and medical sciences / Blood and lymphatic vessels / Bone Marrow Transplantation / Brain / Cardiology. Vascular system / CD36 Antigens - metabolism / CD36/metabolism / Cells / Cells, Cultured / Cellular biology / Cholesterol / Cholesterol - metabolism / Cholesterol, Dietary - administration & dosage / Class A / Cultured / Diet / Diet, Atherogenic / Dietary/administration & dosage / Endothelial cells / Endothelial Cells - physiology / Enzymes / Foam cells / Foam Cells - metabolism / Genetic aspects / Immunologic/genetics/metabolism / Inbred C57BL / Individualized Instruction / Knockout / LDL/metabolism / Life Sciences / Lipids / Lipoproteins / Lipoproteins, LDL - metabolism / Macrophages / Macrophages - metabolism / Macrophages, Peritoneal - physiology / Medical and Health Sciences / Medical sciences / Medicin och hälsovetenskap / Mice / Mice, Inbred C57BL / Mice, Knockout / Mitogen-Activated Protein Kinase 8 - metabolism / Mitogen-Activated Protein Kinase 9 - genetics / Mitogen-Activated Protein Kinase 9 - metabolism / Mitogen-Activated Protein Kinase 9/genetics/metabolism / Muscle / Muscle, Smooth, Vascular - cytology / Myocytes / Myocytes, Smooth Muscle - physiology / Obesity / Pathology / Peritoneal/physiology / Phosphorylation / Proteins / Receptors / Receptors, Immunologic - genetics / Receptors, Immunologic - metabolism / Receptors, Scavenger / Scavenger / Scavenger Receptors / Scavenger Receptors, Class A / Smooth / Smooth Muscle/physiology / Statistical Analysis / Statistical Significance / T lymphocytes / T-Lymphocytes - immunology / Vascular/cytology