Objective: Four-and-a-half LIM domain protein-2 (FHL2) is expressed in endothelial cells, vascular smooth muscle cells, and leukocytes. It regulates cell survival, migration, and inflammatory response, but its role in atherogenesis is unknown.
Approach And Results: To investigate the role of FHL2 in atherosclerosis, FHL2-deficient mice were crossed with ApoE-deficient mice, to generate ApoE/FHL2-/- mice. After high-fat diet, ApoE/FHL2-/- mice had significantly smaller atherosclerotic plaques than ApoE-/- mice in the aortic sinus, the brachiocephalic artery, and the aorta. This was associated with enhanced collagen and smooth muscle cell contents and a 2-fold reduction in macrophage content within the plaques of ApoE/FHL-2-/- versus ApoE-/- mice. This could be explained, in part, by the reduction in aortic ICAM-1 (intracellular adhesion molecule) mRNA and VCAM-1 (vascular cell adhesion molecule) protein expression in the plaque. Aortic gene expression of the chemokines CX3CL1 and CCL5 was increased in ApoE/FHL2-/- versus ApoE-/- mice. Peritoneal thioglycollate injection elicited equivalent numbers of monocytes and macrophages in both groups, but a significantly lower number of proinflammatory Ly6C high monocytes were recruited in ApoE/FHL2-/- versus ApoE-/- mice. Furthermore, mRNA levels of CX3CR1 were 2-fold higher in monocytes from ApoE/FHL2-/- versus ApoE-/- mice. Finally, we investigated the potential importance of myeloid cell FHL2 deficiency in atherosclerosis. After being irradiated, ApoE-/- or ApoE/FHL2-/- mice were transplanted with ApoE-/- or ApoE/FHL2-/- bone marrow. After high-fat diet, both chimeric groups developed smaller plaques than ApoE-/- transplanted with ApoE-/- bone marrow.
Conclusions: These results suggest that FHL2 in both myeloid and vascular cells may play an important role in atherosclerosis by promoting proinflammatory chemokine production, adhesion molecule expression, and proinflammatory monocyte recruitment.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1161/ATVBAHA.114.305071 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Near-infrared light therapy normalizes amyloid load, neuronal lipid membrane order, rafts and cholesterol level in Alzheimer's disease.
J Photochem Photobiol B
December 2024
Center for Biomedical Photonics, College of Physics and Optoelectronic Engineering, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, Shenzhen University, Shenzhen 518060, PR China. Electronic address:
Cholesterol dysregulation, disorder of neuronal membrane lipid packing, and lipid rafts lead to the synthesis and accumulation of toxic amyloid-β (Aβ), contributing to the development of Alzheimer's disease (AD). Our study shows that near-infrared (NIR) transcranial photobiomodulation therapy (tPBMT) can reduce Aβ load and restore the properties of neuronal plasma membrane, including Aβ production, bilayer order, rafts, lipid content, and Ca channels during AD. Mice in the experiments were exposed to 808-nm LED for 1 h daily over 3 months.
View Article and Find Full Text PDFUnc5b prevents macrophage-derived foam cell migration and promotes atherosclerotic development via the P53-cuproptosis signaling pathway.
Life Sci
December 2024
College of Basic Medicine, Inner Mongolia Medical University, Hohhot 010110, PR China; Medical Experiments Center, Inner Mongolia Medical University, Hohhot 010110, PR China. Electronic address:
Background: Atherosclerosis involves the buildup of macrophage-derived foam cells in the arterial intima. Facilitating the egress of these cells from plaques can significantly slow disease progression. The transmembrane receptor Unc5b, a vascular-specific axon guidance receptor, is upregulated in foam cells, and inhibits their migration from the plaques.
View Article and Find Full Text PDFNox1/PAK1 is required for angiotensin II-induced vascular inflammation and abdominal aortic aneurysm formation.
Redox Biol
December 2024
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Guizhou Medical University, Gui'an, 561113, Guizhou, PR China. Electronic address:
NADPH oxidase 1 (Nox1) is a major isoform of Nox in vascular smooth muscle cells (VSMCs). VSMC activation and extracellular matrix (ECM) remodelling induce abdominal aortic aneurysm (AAA). In this study, we aim to determine the role of Nox1 in the progression of AAA and explore the underling mechanism.
View Article and Find Full Text PDFTTK Inhibition Alleviates Postinjury Neointimal Formation and Atherosclerosis.
Adv Sci (Weinh)
December 2024
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Atherosclerosis and its associated cardio-cerebrovascular complications remain the leading causes of mortality worldwide. Current lipid-lowering therapies reduce only approximately one-third of the cardiovascular risk. Furthermore, vascular restenosis and thrombotic events following surgical interventions for severe vascular stenosis significantly contribute to treatment failure.
View Article and Find Full Text PDFComparative lipidomic and metabolomic profiling of mdx and severe mdx-apolipoprotein e-null mice.
Skelet Muscle
December 2024
Department of Physiology and Aging, University of Florida, Gainesville, FL, USA.
Despite its notoriously mild phenotype, the dystrophin-deficient mdx mouse is the most common model of Duchenne muscular dystrophy (DMD). By mimicking a human DMD-associated metabolic comorbidity, hyperlipidemia, in mdx mice by inactivating the apolipoprotein E gene (mdx-ApoE) we previously reported severe myofiber damage exacerbation via histology with large fibro-fatty infiltrates and phenotype humanization with ambulation dysfunction when fed a cholesterol- and triglyceride-rich Western diet (mdx-ApoE). Herein, we performed comparative lipidomic and metabolomic analyses of muscle, liver and serum samples from mdx and mdx-ApoE mice using solution and high-resolution-magic angle spinning (HR-MAS) H-NMR spectroscopy.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!