ArticleArteriosclerosis, thrombosis, and vascular biology2012
G protein-coupled receptor kinase-5 attenuates atherosclerosis by regulating receptor tyrosine kinases and 7-transmembrane receptors.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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Who cites it
33 citing papers in PubMed, 45 citations in OpenAlex.
- Abnormal lipid metabolism and atherosclerosis: a new perspective on organelle function regulation and ferroptosis.Frontiers in immunology · 2025Article
- G protein-coupled receptor kinase 5 regulates thrombin signaling in platelets.Research and practice in thrombosis and haemostasis · 2024Article
- GRK5 is an essential co-repressor of the cardiac mineralocorticoid receptor and is selectively induced by finerenone.World journal of cardiology · 2022Article
- Drebrin attenuates atherosclerosis by limiting smooth muscle cell transdifferentiation.Cardiovascular research · 2022Article
- GRK5 Deficiency Causes Mild Cognitive Impairment due to Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2022Review
- Review
- The GRKs Reactome: Role in Cell Biology and Pathology.International journal of molecular sciences · 2021Review
- Targeting GRK5 for Treating Chronic Degenerative Diseases.International journal of molecular sciences · 2021Review
- Antagonistic Roles of GRK2 and GRK5 in Cardiac Aldosterone Signaling Reveal GRK5-Mediated Cardioprotection via Mineralocorticoid Receptor Inhibition.International journal of molecular sciences · 2020Article
- Drebrin regulates angiotensin II-induced aortic remodelling.Cardiovascular research · 2018Article
- USP20 (Ubiquitin-Specific Protease 20) Inhibits TNF (Tumor Necrosis Factor)-Triggered Smooth Muscle Cell Inflammation and Attenuates Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Single Nucleotide Polymorphisms in the G-Protein Coupled Receptor Kinase 5 (GRK5) Gene are associated with Plasma LDL-Cholesterol Levels in Humans.Scientific reports · 2018Article
- GRK5 functions as an oncogenic factor in non-small-cell lung cancer.Cell death & disease · 2018Article
- G-protein-coupled receptor kinase-5 promotes glioblastoma progression by targeting the nuclear factor kappa B pathway.American journal of translational research · 2018Article
- GRK5 - A Functional Bridge Between Cardiovascular and Neurodegenerative Disorders.Frontiers in pharmacology · 2018Review
- Mycobacteria exploit nitric oxide-induced transformation of macrophages into permissive giant cells.EMBO reports · 2017Article
- Interleukin-9 mediates chronic kidney disease-dependent vein graft disease: a role for mast cells.Cardiovascular research · 2017Article
- The influence of two functional genetic variants of GRK5 on tau phosphorylation and their association with Alzheimer's disease risk.Oncotarget · 2017Article
- Proinflammatory Cytokines Mediate GPCR Dysfunction.Journal of cardiovascular pharmacology · 2017Review
- C-X-C Motif Chemokine Receptor 3 Splice Variants Differentially Activate Beta-Arrestins to Regulate Downstream Signaling Pathways.Molecular pharmacology · 2017Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
objectiveG protein-coupled receptor kinase-5 (GRK5) is a widely expressed Ser/Thr kinase that regulates several atherogenic receptors and may activate or inhibit nuclear factor-κB (NF-κB). This study sought to determine whether and by what mechanisms GRK5 affects atherosclerosis. METHODS AND
resultsGrk5(-/-)/Apoe(-/-) mice developed 50% greater aortic atherosclerosis than Apoe(-/-) mice and demonstrated greater proliferation of macrophages and smooth muscle cells (SMCs) in atherosclerotic lesions. In Apoe(-/-) mice, carotid interposition grafts from Grk5(-/-) mice demonstrated greater upregulation of cell adhesion molecules than grafts from wild-type mice and, subsequently, more atherosclerosis. By comparing Grk5(-/-) with wild-type cells, we found that GRK5 desensitized 2 key atherogenic receptor tyrosine kinases: the platelet-derived growth factor receptor-β in SMCs, by augmenting ubiquitination/degradation; and the colony-stimulating factor-1 receptor (CSF-1R) in macrophages, by reducing CSF-1-induced tyrosyl phosphorylation. GRK5 activity in monocytes also reduced migration promoted by the 7-transmembrane receptor for monocyte chemoattractant protein-1 CC chemokine receptor-2. Whereas GRK5 diminished NF-κB-dependent gene expression in SMCs and endothelial cells, it had no effect on NF-κB activity in macrophages.
conclusionsGRK5 attenuates atherosclerosis through multiple cell type-specific mechanisms, including reduction of SMC and endothelial cell NF-κB activity and desensitization of receptor-specific signaling through the monocyte CC chemokine receptor-2, macrophage CSF-1R, and the SMC platelet-derived growth factor receptor-β.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.