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Neferine improves cardiac remodeling induced by hypertension by modulating multiple signaling pathways --heart

ABSTRACT: The goals of this study is to compare the differently expressed genes in heart tissue of WKY and SHR with or withoutneferine treatment. The SHRs were randomly divided into 2 groups: SHR, and SHR +neferine (10mg/kg/d) groups . WKY rats were set as control. Rats in WKY and SHR groups were intragastrically with double distilled water (dd H2O), while rats in SHR + neferine (10mg/kg/d) group were intragastrically with 10 mg/kg/d of neferine for 10 weeks. Then the heart tissues were used to identify differentially expressed genes among different groups.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE249274 | GEO | 2025/11/20

REPOSITORIES: GEO

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Project description:Background: The vascular wall of small arteries is heavily affected by high blood pressure. However, the underlying mechanisms causing vascular changes are not fully elucidated. Using a novel data-independent acquisition mass spectrometry (DIA-MS) approach, we aimed to determine the proteomic changes in small mesenteric arteries during early-onset high blood pressure in a rat model of hypertension. Methods: Snap frozen small mesenteric and renal arteries from the spontaneous hypertension rat (SHR) model and Wistar Kyoto (WKY) control rats were collected from two time points (6- and 12-weels of age) and analyzed by a label free quantitative DIA-MS workflow. Mesenteric arteries from Wister Hannover rats were included as an additional control to clarify genetic drift caused by selective inbreeding. Results: We identified a total of 3956 consistent proteins in the mesenteric artery wall and found that 286 proteins were significantly regulated in 12-weeks old SHRs compared to WKY controls. Comparing to an in silico matrisome database, we identified 38 extracellular matrix-associated proteins that could distinguish SHRs from WKY controls. Furthermore, when comparing the significantly regulated proteins identified in mesenteric and renal arteries, we identified 18 proteins, including Serpina3l, Igg-2a, ENSRNOG00000049829, Acyp2, Enpp3, Lss, Acaa1a, Basp1, an isoform of Basp1, Flot1, Flot2, Gstt1, Nit1, Ppid, Ikbkap, Poglut3, P4ha2 and Usp15, that were changed in both vascular beds. These proteins were associated with vital cellular processes, such as dyslipidemia, protease inhibition, remodeling and generation of reactive oxygen species. Majority of the identified proteins and pathways were associated with hypertension, and mapping the underlying changes help understanding the pathological processes occurring in the arterial wall during early-onset hypertension. Conclusions: Our data provides an in-depth analysis of the proteomic architecture of the mesenteric and renal artery wall from SHRs and WKY control rats. We identified 18 novel candidate proteins that highlights critical changes in small arteries of the SHR.

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Neferine improves cardiac remodeling induced by hypertension by modulating multiple signaling pathways --heart

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