Dataset Information

Study on biomarkers of homocysteine-induced transformation of vascular smooth muscle cells into foam cells

ABSTRACT: Objective: Foam cells, predominantly originating from vascular smooth muscle cells (VSMCs) and macrophages, are a hallmark of atherosclerotic plaque development. Strategies aimed at inhibiting foam cell formation have emerged as pivotal for atherosclerosis (AS) prevention and therapy. Homocysteine (Hcy), recognized as an independent risk factor for AS, has been shown to trigger the phenotypic transition of VSMCs into foam cells; however, the molecular mechanisms underlying this process remain incompletely elucidated. The present study aimed to identify crucial regulatory proteins and elucidate the mechanistic pathways involved in Hcy-induced foam cell formation from VSMCs, thereby offering a theoretical framework for AS intervention. Methods: VSMCs were allocated into two groups: a control cohort and a group exposed to Hcy to simulate an AS-like state. Quantitative proteomic profiling was performed using 4D Fast-DIA approach to detect differentially expressed proteins between these groups. To explore functional implications, enrichment analyses involving Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were conducted. Protein-protein interaction networks were constructed using the STRING database to identify central interactors. Target proteins were subsequently validated through parallel reaction monitoring (PRM). Furthermore, histological analyses including hematoxylin and eosin (HE) staining, Oil Red O staining, Western blot, and biochemical analysis were utilized to confirm the role and mechanism of identified proteins in the context of Hcy-driven foam cell conversion. Results: Proteomic analysis identified 4804 proteins, with 4799 proteins being quantitatively comparable. A total of 54 proteins displayed significant differential expression based on thresholds of p < 0.05 and fold change > 1.5 or < 1/1.5. Among them, 13 proteins were upregulated, while 41 were downregulated in response to Hcy treatment. PRM validation focused on 16 candidate proteins: COX7C, STX5, UBQLN2, DDX50, TBCB, GSR, PCNP, CDV3, PEBP1, PPIA, S100A6, EIF4E2, UBQLN1, ARMC1, NUDCD2, and H1-2. Histological staining demonstrated enhanced lipid accumulation and morphological changes indicative of foam cell transformation in Hcy-treated VSMCs. The protein levels of COX7C, and sterol regulatory element-binding proteins (SREBP1C and SREBP2) were elevated upon Hcy exposure. Overexpression of COX7C further augmented the expression of SREBP1C and SREBP2, exacerbated lipid accumulation, and promoted foam cell transformation in Hcy-treated VSMCs. On the other hand, knockdown of COX7C had the opposite effects. Conclusion: COX7C serves as a central regulatory protein in Hcy-induced transformation of VSMCs into foam cells. Its pathogenic role is likely mediated through the upregulation of SREBP1C and SREBP2, thereby promoting lipid accumulation. These findings provide new insights into AS pathogenesis and identify COX7C as a potential therapeutic target.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Vascular Smooth Muscle Cell

SUBMITTER: minghao zhang

LAB HEAD: Minghao Zhang

PROVIDER: PXD064315 | Pride | 2026-02-16

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	XB02401DA_Control1_B1_1_30148.d.zip	Other
	XB02401DA_Control2_B2_1_30149.d.zip	Other
	XB02401DA_Control3_B3_1_30150.d.zip	Other
	XB02401DA_Hcy1_B4_1_30152.d.zip	Other
	XB02401DA_Hcy2_B5_1_30153.d.zip	Other

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Publications

Study on biomarkers of homocysteine-induced transformation of vascular smooth muscle cells into foam cells.

Wang Xiuyu X Ma Xinpeng X Zhang Xiang X Ma Xing X Zhang Minghao M

Scientific reports 20260205

Homocysteine (Hcy) is an independent risk factor for atherosclerosis (AS). Hcy induces the transformation of vascular smooth muscle cells (VSMCs) into foam cells, which play a crucial role in this process. However, the detailed mechanism is still unclear. To identify the key regulatory proteins during this process and clarify the possible mechanism of Hcy-induced foam cell formation in VSMCs, thereby providing theoretical support for the intervention of AS. VSMCs were allocated into two groups: ...[more]

PMID: 41644998

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