ArticleCell biology and toxicology2023
Herpud1 deficiency alleviates homocysteine-induced aortic valve calcification.
Article in Cell biology and toxicology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- BHMT Protects Against Diabetic Cataracts by Reducing Homocysteine and Counteracting Endoplasmic Reticulum Stress in Lens Epithelial Cells.Applied biochemistry and biotechnology · 2026Article
- Single-cell sequencing combined with transcriptome sequencing to reveal the molecular mechanisms related to integrated stress responses in atherosclerosis.Journal of cardiothoracic surgery · 2026Article
- Dysregulated homocysteine metabolism and cardiovascular disease and clinical treatments.Molecular and cellular biochemistry · 2025Review
- High-Sensitivity Troponins and Homocysteine: Combined Biomarkers for Better Prediction of Cardiovascular Events.International journal of molecular sciences · 2025Review
- Machine learning assists regulated cell death crucial biomarker selection in adenocarcinoma of the lung: biological data testing and cell assay determination.Discover oncology · 2025Article
- Valvular calcification in chronic kidney disease: new insights from recent clinical and preclinical studies.Clinical kidney journal · 2025Article
- Investigation of autophagy‑related genes and immune infiltration in calcific aortic valve disease: A bioinformatics analysis and experimental validation.Experimental and therapeutic medicine · 2024Article
- Valsartan Attenuated Homocysteine-Induced Impaired Autophagy and ER Stress in Human Umbilical Vein Endothelial Cells.Cardiovascular therapeutics · 2023Article
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
objectivesTo evaluate the role and therapeutic value of homocysteine (hcy)-inducible endoplasmic reticulum stress (ERS) protein with ubiquitin like domain 1 (Herpud1) in hcy-induced calcific aortic valve disease (CAVD).
backgroundThe morbidity and mortality rates of calcific aortic valve disease (CAVD) remain high while treatment options are limited.
methodsIn vivo, we use the low-density lipoprotein receptor (LDLR) and Herpud1 double knockout (LDLR-/-/Herpud1-/-) mice and used high methionine diet (HMD) to assess of aortic valve calcification lesions, ERS activation, autophagy, and osteogenic differentiation of aortic valve interstitial cells (AVICs). In vitro, the role of Herpud1 in the Hcy-related osteogenic differentiation of AVICs was investigated by manipulating of Herpud1 expression.
resultsHerpud1 was highly expressed in calcified human and mouse aortic valves as well as primary aortic valve interstitial cells (AVICs). Hcy increased Herpud1 expression through the ERS pathway and promoted CAVD progression. Herpud1 deficiency inhibited hcy-induced CAVD in vitro and in vivo. Herpud1 silencing activated cell autophagy, which subsequently inhibited hcy-induced osteogenic differentiation of AVICs. ERS inhibitor 4-phenyl butyric acid (4-PBA) significantly attenuated aortic valve calcification in HMD-fed low-density lipoprotein receptor-/- (LDLR-/-) mice by suppressing ERS and subsequent Herpud1 biosynthesis.
conclusionsThese findings identify a previously unknown mechanism of Herpud1 upregulation in Hcy-related CAVD, suggesting that Herpud1 silencing or inhibition is a viable therapeutic strategy for arresting CAVD progression. HIGHLIGHTS: • Herpud1 is upregulated in the leaflets of Hcy-treated mice and patients with CAVD. • In mice, global knockout of Herpud1 alleviates aortic valve calcification and Herpud1 silencing activates cell autophagy, inhibiting osteogenic differentiation of AVICs induced by Hcy. • 4-PBA suppressed Herpud1 expression to alleviate AVIC calcification in Hcy treated AVICs and to mitigate aortic valve calcification in mice.
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