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CA1 significantly aggravats atherosclerosis and MTZ, a inhibitor of CA1, can alleviate the disease.

ABSTRACT: Aortic calcification is essential for atherosclerosis (AS). Carbonic anhydrase I (CA1) can promote calcification in aortic tissues to stimulate AS plaque formation, and methazolamide (MTZ), a CA inhibitor, can be used to treat AS by inhibiting CA1-mediated calcification. This study used an established a CA1 [+/+] KI Apoe [-/-] mice to confirm stimulatory role of CA1 on AS and the therapeutic effect of MTZ and investigate the mechanism. In this study, Apoe [-/-] mice with CA1 overexpression were induced to AS by administrating high-fat food. The present study confirmed that CA1 is AS-therapeutic target by mediating the proportions of B1/MZB-1 cells, CD8+T cells, CD11c+ macrophages and CD11c- macrophages as well as their AS-related gene expressions and focal adhesion pathway. MTZ can be used for AS therapy.

ORGANISM(S): Mus musculus

PROVIDER: GSE253001 | GEO | 2026/01/19

REPOSITORIES: GEO

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Methazolamide can treat atherosclerosis

Project description:Methoxazolamide (MTZ) has been confirmed to treat atherosclerosis (AS) by inhibiting calcification in aortic tissues. This study investigated the therapeutic mechanism. In this study, ApoE-/- mice were fed a high-fat diet to establish an AS model and then treated with MTZ. The aortic tissues were analyzed using single-cell sequencing. MTZ significantly increased the proportions of B-1/MZB cells, CD8+CD122+ Treg-like cell. Those cells can exert atheroprotective role by suppressing immune response and proinflammation. Meanwhile, MTZ decreased the proportions of nonclassical CD14+CD16++ monocytes and Spp1+ macrophages. Those cells can exert atherogenic role by suppressing proinflammation, calcification and tissue remodeling. The result suggested that MTZ is a potential anti-AS drug that regulates proportions of immunosuppressive cells and proinflammatory cells as well as their calcification-stimulating gene expression.

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A novel long noncoding RNA SNHG3 promotes osteoblast differentiation through BMP2 upregulation in calcific aortic valve disease

Project description:The role of long noncoding RNAs (lncRNAs) in calcific aortic valve disease (CAVD) remains largely elusive. This study aims to report a novel therapeutic lncRNA, SNHG3, and elucidate its role in CAVD. Based on high-throughput transcriptomic sequencing of human aortic valves, SNHG3 is among the most highly expressed lncRNAs in CAVD. Furthermore, SNHG3 upregulation is verified in human calcified aortic valves, osteoblastic human aortic valve interstitial cells (hVICs), and aortic valve tissues in CAVD mice. Moreover, knockdown of SNHG3 with antisense oligonucleotide markedly ameliorates aortic valve calcification in high cholesterol diet-treated ApoE-/- mice, as evidenced by reduced calcium deposition in the aortic valve leaflets, improved echocardiographic parameters, and decreased osteogenic differentiation markers (RUNX2, osteopontin, and osteocalcin) in aortic valves. Consistent with these in vivo findings, SNHG3 overexpression aggravates the calcification of hVICs, while knockdown of SNHG3 alleviates the process of differential calcification. Transcriptomics sequencing, gene set enrichment analyses, RNA-pull down, RNA immunoprecipitation and chromatin immunoprecipitation-qPCR show that SNHG3 physically interacts with polycomb repressive complex 2 to suppress the H3K27 tri-methylation BMP2 locus, which in turn activates BMP2 expression and signaling pathways. Taken together, SNHG3 promotes aortic valve calcification by upregulating BMP2, which might be a novel therapeutic target in human CAVD.

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carbonic anhydrase (1 or 2) simple or double mutants-Comparative transcriptome analysis between carbonic anhydrase mutants and wild type Arabidopsis

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2012-03-25 | GSE36625 | GEO

carbonic anhydrase (1 or 2) simple or double mutants-Comparative transcriptome analysis between carbonic anhydrase mutants and wild type Arabidopsis

2012-03-25 | E-GEOD-36625 | biostudies-arrayexpress

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2014-05-02 | E-MTAB-2409 | biostudies-arrayexpress

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Project description:Aortic valve calcification is the most common form of valvular heart disease, but the mechanisms of calcific aortic valve disease (CAVD) are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development of CAVD is not well understood. The aim of this study was to investigate the molecular changes that occur with inhibition of Notch signaling in the aortic valve. Notch signaling pathway members are expressed in adult aortic valve cusps, and examination of diseased human aortic valves revealed decreased expression of NOTCH1 in areas of calcium deposition. To identify downstream mediators of Notch1, we examined gene expression changes that occur with chemical inhibition of Notch signaling in rat aortic valve interstitial cells (AVICs). We found significant downregulation of Sox9 along with several cartilage-specific genes that were direct targets of the transcription factor, Sox9. Loss of expression Sox9 has been published to be associated with aortic valve calcification. Utilizing an in vitro porcine aortic valve calcification model system, inhibition of Notch activity resulted in accelerated calcification while stimulation of Notch signaling attenuated the calcific process. Finally, the addition of Sox9 was able to prevent the calcification of porcine AVICs that occurs with Notch inhibition. In conclusion, loss of Notch signaling contributes to aortic valve calcification via a Sox9-dependent mechanism. 3 samples of aortic valve interstitial cells treated with DAPT were compared with 3 samples of aortic valve interstitial cells treated with DMSO

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