Fibroblast Activation Protein Regulates Lesion Burden and the Fibroinflammatory Response in Apoe-Deficient Mice in a Sexually Dimorphic Manner

Monslow, James; Todd, Leslie; Chojnowski, John E.; Govindaraju, Priya; Assoian, Richard K.; Puré, Ellen

doi:10.1016/j.ajpath.2020.01.004

Cited by 10 publications

(16 citation statements)

References 62 publications

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“…marked vascular smooth muscle cells with a proliferative and matrix-producing tendency in atherosclerotic mice (12). In accordance with pioneering results, elevated FAP expression in thin fibrous cap and fibrosis, collagen-rich tissue in intima was both detected in our immunohistological findings.…”

Section: Monslow Et Al Demonstrated Co-localization Of Fap and Vascul...supporting

confidence: 93%

Feasibility of In Vivo Imaging of Fibroblast Activation Protein in Human Arterial Walls

Ning

et al. 2021

J Nucl Med

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Increased expression of fibroblast activating protein (FAP) in fibrous caps may contribute to progression of atherosclerotic plaques. Methods Forty-one patients who underwent gallium-68conjugated quinoline-based FAP inhibitor ( 68 Ga-FAPI-04) PET/CT for non-cardiovascular indications were retrospectively analyzed. Correlations were assessed between the uptake of 68 Ga-FAPI-04 in large arterial walls (SUVmax and target-to-background ratio, TBR) and degree of calcification and cardiovascular risk factors. Results Focal arterial uptake of 68 Ga-FAPI-04 or calcification was detected in 1,177 arterial segments in all 41 patients. TBR was negatively correlated with the degree of calcification (Hounsfield Units, HU) (r = -0.27, P < 0.01). Mean TBR in higher-risk patients was greater than lower-risk patients (2.2 ± 0.3 vs. 1.8 ± 0.3, P < 0.01).Immunohistochemical labeling of carotid plaques exhibited prominent FAP expression in a thin fibrous cap and moderate FAP expression in a thick cap. Conclusion 68 Ga-FAPI-04 PET/CT might have potential for imaging fibroblastic activation in the arterial wall.

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Section: Monslow Et Al Demonstrated Co-localization Of Fap and Vascul...supporting

confidence: 93%

Feasibility of In Vivo Imaging of Fibroblast Activation Protein in Human Arterial Walls

Ning

et al. 2021

J Nucl Med

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“… 15 Moreover, there is little overlap of FAP+ fibroblasts with fibroblasts expressing α-smooth muscle actin (α-SMA), generally considered a marker of HSC activation and fibrogenesis. 16 , 17 The gene expression profile of FAP+ fibroblasts is enriched for inflammatory genes, 18 , 19 , 20 , 21 suggesting that FAP-expressing fibroblasts drive inflammation during chronic wound healing. Still, the function of FAP and FAP-expressing fibroblasts and HSCs in chronic (liver) injury and fibrosis remains elusive.…”

mentioning

confidence: 99%

Fibroblast Activation Protein Activates Macrophages and Promotes Parenchymal Liver Inflammation and Fibrosis

Yang

Kim

Yan

et al. 2023

Cellular and Molecular Gastroenterology and Hepatology

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“…Of note, FAP is expressed in atherosclerotic plaques but its role in regulating inflammatory and fibrotic response is still poorly understood [ 7 , 8 , 31 ]. Two recent studies reported contrasting data: Monslow et al demonstrated that global deletion of FAP in ApoE −/− mice accelerated atherosclerotic disease progression by altering macrophage infiltration into the vulnerable plaque [ 31 ]. Instead, Stein et al reported that deletion of FAP in ApoE −/− mice resulted in decreased atherosclerotic plaque formation [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic ablation of fibroblast activation protein alpha attenuates left ventricular dilation after myocardial infarction

et al. 2021

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Introduction Regulating excessive activation of fibroblasts may be a promising target to optimize extracellular matrix deposition and myocardial stiffness. Fibroblast activation protein alpha (FAP) is upregulated in activated fibroblasts after myocardial infarction (MI), and alters fibroblast migration in vitro. We hypothesized that FAP depletion may have a protective effect on left ventricular (LV) remodeling after MI. Materials and methods We used the model of chronic MI in homozygous FAP deficient mice (FAP-KO, n = 51) and wild type mice (WT, n = 55) to analyze wound healing by monocyte and myofibroblast infiltration. Heart function and remodeling was studied by echocardiography, morphometric analyses including capillary density and myocyte size, collagen content and in vivo cell-proliferation. In non-operated healthy mice up to 6 months of age, morphometric analyses and collagen content was assessed (WT n = 10, FAP-KO n = 19). Results Healthy FAP-deficient mice did not show changes in LV structure or differences in collagen content or cardiac morphology. Infarct size, survival and cardiac function were not different between FAP-KO and wildtype mice. FAP-KO animals showed less LV-dilation and a thicker scar, accompanied by a trend towards lower collagen content. Wound healing, assessed by infiltration with inflammatory cells and myofibroblasts were not different between groups. Conclusion We show that genetic ablation of FAP does not impair cardiac wound healing, and attenuates LV dilation after MI in mice. FAP seems dispensable for normal cardiac function and homeostasis.

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Fibroblast Activation Protein Regulates Lesion Burden and the Fibroinflammatory Response in Apoe-Deficient Mice in a Sexually Dimorphic Manner

Cited by 10 publications

References 62 publications

Feasibility of In Vivo Imaging of Fibroblast Activation Protein in Human Arterial Walls

Feasibility of In Vivo Imaging of Fibroblast Activation Protein in Human Arterial Walls

Fibroblast Activation Protein Activates Macrophages and Promotes Parenchymal Liver Inflammation and Fibrosis

Genetic ablation of fibroblast activation protein alpha attenuates left ventricular dilation after myocardial infarction

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