Secreted Frizzled Related Proteins in Cardiovascular and Metabolic Diseases

Guan, Hua; Jin, Zhang; Luan, Jing; Xu, Hao; Huang, Zhenghao; Yu, Qi; Gou, Xin; Xu, Lina

doi:10.3389/fendo.2021.712217

Cited by 19 publications

(7 citation statements)

References 167 publications

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“…[43][44][45] SFRP1, a member of the secreted frizzled-related glycoprotein family that act as extracellular signaling ligands and modulators of Wnt/β-catenin signal transduction pathways, is ubiquitously expressed and has been implicated in cardiac remodeling and fibrosis. 46,47 A nested case-control study from a cohort of middle-aged women demonstrated increased blood concentrations of SFRP1 to be a predictor of cardiovascular events. 48 The principal strengths of our study include the prospective cohort design of the CHS, with adjudicated IS events and subtypes.…”

Section: Discussionmentioning

confidence: 99%

Plasma Proteomic Associations With Incident Ischemic Stroke in Older Adults

et al. 2023

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Background:Plasma proteomics may elucidate novel insights into the pathophysiology of ischemic stroke (IS), identify biomarkers of IS risk, and guide development of nascent prevention strategies. We evaluated the relationship between the plasma proteome and IS risk in the population-based Cardiovascular Health Study (CHS).Methods:Eligible CHS participants were free of prevalent stroke and underwent quantification of 1298 plasma proteins using the aptamer-based SOMAScan assay platform from the 1992-1993 study visit. Multivariable Cox proportional hazards regression was used to evaluate associations between a 1-standard deviation increase in the log-2 transformed estimated plasma protein concentrations and incident IS, adjusting for demographics, IS risk factors, and estimated glomerular filtration rate. For proteins independently associated with incident IS, a secondary stratified analysis evaluated associations in subgroups defined by sex and race. Exploratory analyses evaluated plasma proteomic associations with cardioembolic and non-cardioembolic IS as well as proteins associated with IS risk in participants with left atrial dysfunction but without atrial fibrillation.Results:Of 2983 eligible participants, the mean age was 74.3 (± 4.8) years, 61.2% were women, and 15.4% were Black. Over a median follow-up of 12.6 years, 450 participants experienced an incident IS. N-terminal pro-brain natriuretic peptide (NTproBNP, adjusted HR 1.37, 95% CI 1.23-1.53, P=2.08x10-08) and macrophage metalloelastase (MMP12, adjusted HR 1.30, 95% CI 1.16-1.45, P=4.55x10-06) were independently associated with IS risk. These two associations were similar in men and women and in Black and non-Black participants. In exploratory analyses, NTproBNP was independently associated with incident cardioembolic IS, E-selectin with incident non-cardioembolic IS, and secreted frizzled-related protein 1 with IS risk in participants with left atrial dysfunction.Conclusions:In a cohort of older adults, NTproBNP and MMP12 were independently associated with IS risk. We identified plasma proteomic determinants of incident cardioembolic and non-cardioembolic IS and found a novel protein associated with IS risk in those with left atrial dysfunction.

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Section: Discussionmentioning

confidence: 99%

Plasma Proteomic Associations With Incident Ischemic Stroke in Older Adults

et al. 2023

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“…Similarly, the expression of Sfrp2 , another Wnt signaling pathway component was greatly enhanced in E16.5 cKO hippocampi and VZ/SVZ of neocortices ( Figure 5M-5O ). Although members of the SFRP family were first reported as Wnt inhibitors, Sfrp2 regulates anteroposterior axis elongation, optic nerve development, and cardiovascular and metabolic processes by the promoting or inhibiting Wnt signaling pathway(Guan et al, 2021; Marcos et al, 2015; Satoh, Gotoh, Tsunematsu, Aizawa, & Shimono, 2006; von Marschall & Fisher, 2010),…”

Section: Resultsmentioning

confidence: 99%

KDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors

Zhang

Zhao

Shen

et al. 2023

Preprint

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The hippocampus plays major roles in learning and memory. Similar to other parts of the brain, the development of hippocampus requires precise coordination of patterning, cell proliferation, differentiation, and migration, with both cell-intrinsic and extrinsic mechanisms involved. Here we genetically removed the chromatin-association capability of KDM2B - a key component of the variant Polycomb repressive complex 1 (PRC1) - in the progenitors of developing dorsal telencephalon (Kdm2bΔCxxC) to surprisingly discover that the size of Kdm2bΔCxxC hippocampus, particularly the dentate gyrus, became drastically smaller with disorganized cellular components and structure. Kdm2bΔCxxC mice displayed prominent defects in spatial memory, motor learning and fear conditioning. The differentiation trajectory of the developing Kdm2bΔCxxC hippocampus was greatly delayed, with a significant amount of TBR2-expressing intermediate progenitors stuck along the migratory/differentiation path. Transcriptome and chromatin immunoprecipitation studies of neonatal hippocampi and their progenitors indicated that genes implicated in stemness maintenance, especially components of canonical Wnt signaling, could not be properly silenced by PRC1 and PRC2. Activating the Wnt signaling disturbed hippocampal neurogenesis, recapitulating the effect of KDM2B loss. Together, we unveiled a previously unappreciated gene repressive program mediated by KDM2B that controls progressive fate specifications and cell migration, hence morphogenesis of hippocampus during development.

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“…Previous studies have shown that expression of SFRP4 in human ventricular myocardium correlates with apoptosis-related gene expression [ 37 ]. SFRP4 has been detected during cardiovascular maturation and in the adult heart.…”

Section: Discussionmentioning

confidence: 99%

SFRP4 Reduces Atherosclerosis Plaque Formation in ApoE Deficient Mice

Guan

Liu

et al. 2023

Cardiology Research and Practice

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Secreted frizzled related protein 4 (SFRP4), a member of the SFRPs family, contributes to a significant function in metabolic and cardiovascular diseases. However, there is not enough evidence to prove the antiatherosclerosis effect of SFRP4 in ApoE knock-out (KO) mice. ApoE KO mice were fed a western diet and injected adenovirus (Ad)-SFRP4 through the tail vein for 12 weeks. Contrasted with the control cohort, the area of atherosclerotic plaque in ApoE KO mice overexpressing SFRP4 was reduced significantly. Plasma high-density lipoprotein cholesterol was elevated in the Ad-SFRP4 group. RNA sequence analysis indicated that there were 96 differentially expressed genes enriched in 10 signaling pathways in the mRNA profile of aortic atherosclerosis lesions. The analysis data also revealed the expression of a number of genes linked to metabolism, organism system, and human disease. In summary, our data demonstrates that SFRP4 could play an important role in improving atherosclerotic plaque formation in the aorta.

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Secreted Frizzled Related Proteins in Cardiovascular and Metabolic Diseases

Cited by 19 publications

References 167 publications

Plasma Proteomic Associations With Incident Ischemic Stroke in Older Adults

Plasma Proteomic Associations With Incident Ischemic Stroke in Older Adults

KDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors

SFRP4 Reduces Atherosclerosis Plaque Formation in ApoE Deficient Mice

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