Biology subjects

Hansson, G. K.

Publications and source records attributed to Hansson, G. K..

2 recordsLinked to original sources

bioRxiv2025

NOD1 ligand FK565 promotes atherogenesis and accumulation of NOD1high smooth muscle cells in atherosclerotic lesions

AimsNucleotide-binding oligomerization domain-containing protein (NOD)1 is an intracellular pattern recognition receptor that initiates immune responses upon ligation of molecules such as bacterial peptidoglycan containing a D-glutamyl-meso-diaminopimelic acid (iE-DAP) moiety. NOD1 ligation has been shown to promote vascular inflammation and atherosclerosis. In this study, we investigate the functional role of NOD1 in atherosclerotic plaques and characterize the vascular cells responsible for NOD1 expression and function. Methods and resultsNOD1 was mainly expressed in a subtype of vascular smooth muscle cells (SMC) in human atherosclerotic lesions. In ex vivo cultures, human endarterectomy specimens reacted to NOD1 ligand by activation of mitogen-activated protein kinase (MAPK) pathways, leading to cytokine expression. Levels of NOD1 mRNA were higher in carotid endarterectomy specimens obtained from symptomatic patients compared to asymptomatic ones. NOD1high SMC were also found in arteries of atherosclerosis-prone Ldlr-/- mice. Challenging these mice with a NOD1 agonist resulted in transmural vascular inflammation, severe arterial damage, accelerated atherogenesis throughout the aorta, and evidence of occlusive coronary artery disease. In rats, mechanic injury to carotid arteries promoted NOD1high SMC expansion and neointima formation. In vitro, neointima derived NOD1high SMCs responded to NOD1 ligand exposure by enhanced migration, increased iNOS+ cells and amplified CCL5 production. ConclusionOur findings show that NOD1 promotes vascular inflammation, vascular injury responses and atherosclerosis by acting on a NOD1high subtype of SMC.

immunology↗

bioRxiv2024

Fgf23 expression increases atherosclerotic plaque burden in male ApoE deficient mice

IntroductionComponents of both the innate and adaptive immune system impact on arterial walls in atherosclerosis. Fibroblast growth factor-23 (FGF23) is a phosphate regulating hormone linked to cardiovascular disease (CVD) in patients with and without chronic renal disease. However, it remains controversial whether FGF23 is merely a biomarker or contributes to CVD. Here, we overexpressed FGF23 in ApoE-/- mice to delineate the role of FGF23 in atherogenesis. Methods and Results10-week old ApoE-/- mice received a hydrodynamic tail vein with a plasmid encoding for Fgf23, and were sacrificed 10 weeks later. Fgf23 concentrations increased more than 400-fold in the Fgf23 treated group, remaining high throughout the experiment. Mice in the Fgf23 group developed hypophosphatemia, secondary hyperparathyroidism and a moderate increase in plasma creatinine concentrations. Male ApoE-/- mice exposed to high Fgf23 developed larger atherosclerotic lesions compared to controls, in two different locations of aorta, whereas no differences in plaque burden were seen between female ApoE-/- mice and controls. Serum IL-6 concentrations were increased in the Fgf23 group, associated with a vascular inflammatory response of recruited macrophages and neutrophils, and with a shift of CD4+ T effector cells from Th1 to Th17 and migration of lymphocytes to the spleen. ConclusionFgf23 increases the atherosclerotic burden in male ApoE-/- mice and alters both the innate immune system and T cell subpopulations, generating an inflammatory environment that may promote adverse clinical outcomes associated with Fgf23 excess.

physiology↗