Sclerostin and Vascular Pathophysiology

Catalano, Antonino; Bellone, Federica; Morabito, Nunziata; Corica, Francesco

doi:10.3390/ijms21134779

Cited by 42 publications

(35 citation statements)

References 78 publications

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“…Cardiovascular diseases are a significant health burden with an ever-increasing prevalence and remain the leading causes of morbidity and mortality worldwide ( Shaito et al, 2020 ). HCASMC proliferation and migration are the pathological basis of atherosclerosis ( Catalano et al, 2020 ; Maguire and Xiao, 2020 ). The purpose of the present study was to provide a comprehensive survey of lncRNAs and mRNAs in human coronary arteries and identify differentially expressed lncRNAs and mRNAs and possible regulatory pathways according to the histological classification of atherosclerotic lesions.…”

Section: Discussionmentioning

confidence: 99%

LncRNA Landscape of Coronary Atherosclerosis Reveals Differentially Expressed LncRNAs in Proliferation and Migration of Coronary Artery Smooth Muscle Cells

Zhou

Zhang

et al. 2021

Front. Cell Dev. Biol.

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We aimed to investigate differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in atherosclerosis and validate the expression of lncRNAs and co-expressed target genes in proliferation and migration models of human coronary artery smooth muscle cells (HCASMCs). Ten coronary artery specimens from a subject who died from a heart attack were employed. The pathological analysis was analyzed by hematoxylin and eosin (H&E) staining, and the lncRNAs and mRNAs were identified by RNA sequencing. Bioinformatic analyses were performed to predict possible mechanisms. The proliferation and migration of HCASMCs were induced with oxidized low-density lipoprotein (ox-LDL). Differentially expressed lncRNAs and mRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). In this study, 68 lncRNAs and 222 mRNAs were identified differentially expressed in atherosclerosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the Fanconi anemia pathway may be involved in atherosclerosis. GON4L was found to be the co-localized target gene of LNC_000439, and 14 genes had high correlations with the expression of seven lncRNAs. In addition, nine lncRNA–miRNA–mRNA networks were constructed, and 53 co-expressed gene modules were detected with weighted gene co-expression network analysis (WGCNA). LNC_000684, LNC_001046, LNC_001333, LNC_001538, and LNC_002115 were downregulated, while LNC_002936 was upregulated in proliferation and migration models of HCASMCs. In total, six co-expressed mRNAs were upregulated in HCASMCs. This study suggests that the differentially expressed lncRNAs identified by RNA sequencing and validated in smooth muscle cells may be a target for regulating HCASMC proliferation and migration in atherosclerosis, which will provide a new diagnostic basis and therapeutic target for the treatment of cardiovascular diseases.

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Section: Discussionmentioning

confidence: 99%

LncRNA Landscape of Coronary Atherosclerosis Reveals Differentially Expressed LncRNAs in Proliferation and Migration of Coronary Artery Smooth Muscle Cells

Zhou

Zhang

et al. 2021

Front. Cell Dev. Biol.

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“…The second one tackles the issue of kidney function. Most previous papers focused on sclerostin in patients with moderate/severe chronic kidney disease [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

The Impact of Sclerostin Levels on Long-Term Prognosis in Patients Undergoing Coronary Angiography: A Personalized Approach with 9-Year Follow-Up

Witkowski

Stompór

Kiewisz

et al. 2021

JPM

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Sclerostin might play a role in atherosclerosis development. This study aimed to analyze the impact of baseline sclerostin levels on 9-year outcomes in patients without significant renal function impairment and undergoing coronary angiography. The primary study endpoint was the rate of major cardiovascular events (MACE), defined as a combined rate of myocardial infarction (MI), stroke, or death at 9 years. We included 205 patients with a mean age of 62.9 ± 0.6 years and 70.2% male. Median serum sclerostin concentration was 133.22 pg/mL (IQR 64.0–276.17). At 9 years, in the whole population, the rate of MACE was 34.1% (n = 70), MI: 11.2% (n = 23), stroke: 2.4% (n = 5), and death: 20.5% (n = 42). In the high sclerostin (>median) group, we observed statistically significant higher rates of MACE and death: 25.2% vs. 43.1% (HR 1.75, 95% CI 1.1–2.10, p = 0.02) and 14.6% vs. 26.5% (HR 1.86, 95% CI 1.02–3.41, p = 0.049), respectively. Similar relationships were observed in patients with chronic coronary syndrome and SYNTAX 0–22 subgroups. Our results suggest that sclerostin assessment might be useful in risk stratification, and subjects with higher sclerostin levels might have a worse prognosis.

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“…Qureshi et al demonstrate that circulating SOST levels are associated with vascular calcification, implicating SOST serves as a surrogate marker between CKD-MBD and cardiovascular disease [ 31 ]. From then on, a large number of existing studies in the broader literature have examined the clinical use of SOST in CKD-MBD [ 32 ]. Nonetheless, the clinical use of SOST remains controversial.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effect of Calcimimetics on Osteoclast–Osteoblast Crosslink in Chronic Kidney Disease and Mineral Bone Disease

Hung

Chang

Hsu

et al. 2020

IJMS

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We have previously demonstrated calcimimetics optimize the balance between osteoclastic bone resorption and osteoblastic mineralization through upregulating Wingless and int-1 (Wnt) signaling pathways in the mouse and cell model. Nonetheless, definitive human data are unavailable concerning therapeutic effects of Cinacalcet on chronic kidney disease and mineral bone disease (CKD-MBD) and osteoclast–osteoblast interaction. We aim to investigate whether Cinacalcet therapy improves bone mineral density (BMD) through optimizing osteocytic homeostasis in a human model. Hemodialysis patients with persistently high intact parathyroid hormone (iPTH) levels > 300 pg/mL for more than 3 months were included and received fixed dose Cinacalcet (25 mg/day, orally) for 6 months. Bone markers presenting osteoclast–osteoblast communication were evaluated at baseline, the 3rd and the 6th month. Eighty percent of study patients were responding to Cinacalcet treatment, capable of improving BMD, T score and Z score (16.4%, 20.7% and 11.1%, respectively). A significant correlation between BMD improvement and iPTH changes was noted (r = −0.26, p < 0.01). Nonetheless, baseline lower iPTH level was associated with better responsiveness to Cinacalcet therapy. Sclerostin, an inhibitor of canonical Wnt/β-catenin signaling, was decreased from 127.3 ± 102.3 pg/mL to 57.9 ± 33.6 pg/mL. Furthermore, Wnt-10b/Wnt 16 expressions were increased from 12.4 ± 24.2/166.6 ± 73.3 pg/mL to 33.8 ± 2.1/217.3 ± 62.6 pg/mL. Notably, procollagen type I amino-terminal propeptide (PINP), a marker of bone formation and osteoblastic activity, was increased from baseline 0.9 ± 0.4 pg/mL to 91.4 ± 42.3 pg/mL. In contrast, tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), a marker of osteoclast activity, was decreased from baseline 16.5 ± 0.4 mIU/mL to 7.7 ± 2.2 mIU/mL. Moreover, C-reactive protein levels were suppressed from 2.5 ± 0.6 to 0.8 ± 0.5 mg/L, suggesting the systemic inflammatory burden may be benefited after optimizing the parathyroid–bone axis. In conclusion, beyond iPTH suppression, our human model suggests Cinacalcet intensifies BMD through inhibiting sclerostin expression and upregulating Wnt-10b/Wnt 16 signaling that activates osteoblastic bone formation and inhibits osteoclastic bone resorption and inflammation. From the perspective of translation to humans, this research trial brings a meaningful insight into the osteoblast–osteoclast homeostasis in Cinacalcet therapy for CKD-MBD.

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Sclerostin and Vascular Pathophysiology

Cited by 42 publications

References 78 publications

LncRNA Landscape of Coronary Atherosclerosis Reveals Differentially Expressed LncRNAs in Proliferation and Migration of Coronary Artery Smooth Muscle Cells

LncRNA Landscape of Coronary Atherosclerosis Reveals Differentially Expressed LncRNAs in Proliferation and Migration of Coronary Artery Smooth Muscle Cells

The Impact of Sclerostin Levels on Long-Term Prognosis in Patients Undergoing Coronary Angiography: A Personalized Approach with 9-Year Follow-Up

Therapeutic Effect of Calcimimetics on Osteoclast–Osteoblast Crosslink in Chronic Kidney Disease and Mineral Bone Disease

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