Dataset Information

Quantitative TMT proteomics of brainstem in spontaneously hypertensive rats

ABSTRACT: The brainstem, the core of the central nervous system, plays a vital role in controlling arterial blood pressure and its elevation of hypertension subtypes, especially essential hypertension. Integrative metabolic and proteomic profiling was performed on the brainstem samples of 11-week-old spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar rats, using hydrophilic interaction liquid chromatography-quadrupole/time-of-flight mass spectrometry (HILIC-Q/TOFMS) and nano-liquid chromatography-high-resolution-mass spectrometry (nano-LC-high-resolution-MS) combined with quantitative tandem mass tags (TMT).

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain

SUBMITTER: Cheng Yu

LAB HEAD: Yu Cheng

PROVIDER: PXD021210 | Pride | 2020-09-24

REPOSITORIES: Pride

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Publications

Integrative Metabolic and Proteomic Profiling of the Brainstem in Spontaneously Hypertensive Rats.

Cheng Yu Y Sun Dongmei D Zhu Bangjie B Zhou Wenbin W Lv Chunming C Kou Fang F Wei Hai H

Journal of proteome research 20200915 10

The brainstem, the core of the central nervous system, plays a vital role in controlling arterial blood pressure and its elevation of hypertension subtypes, especially essential hypertension. Integrative metabolic and proteomic profiling was performed on the brainstem samples of 11 week old spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar rats, using hydrophilic interaction liquid chromatography quadrupole/time-of-flight mass spectrometry (HILIC-Q/TOFMS) (PeptideAtlas: ...[more]

PMID: 32869641

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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.

Project description:Abstract Background: Long-term hypertension can lead to hypertensive heart disease, which ultimately progresses to heart failure. As an angiotensin receptor blocker (ARB) antihypertensive drug, allisartan can control blood pressure and improve cardiac remodeling and cardiac dysfunction caused by hypertension. The objective of this study is to investigate the protective effects of Allisartan on the heart of spontaneously hypertensive rats (SHRs) and the underlying mechanisms. Methods: We used spontaneously hypertensive rats (SHRs) as an animal model of hypertensive heart disease and treated them with allisartan orally at a dose of 25 mg/(Kg·day). We continuously monitored the rats' blood pressure levels, measured their body and heart weights, and evaluated their cardiac structure and function using echocardiography. WGA staining and Masson trichrome staining were employed to assess the morphology of the myocardial tissue. We performed transcriptome and proteome analysis using the Solexa/Illumina sequencing platform and tandem mass tag (TMT) technology, respectively. We used immunofluorescence co-localization to analyze Nrf2 nuclear translocation, and TUNEL to detect the level of cell apoptosis. The protein and mRNA levels were determined by Western blotting and qRT-PCR, respectively. Results: Allisartan lowered blood pressure, attenuated cardiac remodeling, and improved cardiac function. Allisartan alleviated cardiomyocyte hypertrophy and cardiac fibrosis. Allisartan significantly affected the pentose phosphate pathway, fatty acid elongation, valine, leucine and isoleucine degradation, glutathione metabolism, and amino sugar and nucleotide sugar metabolism pathways in the hearts of SHRs, and upregulated the expression level of GSTM2. Allisartan activated the PI3K-AKT-Nrf2 signaling pathway and inhibited cardiomyocyte apoptosis. Conclusions: Our study determined that allisartan effectively controls blood pressure in SHRs and improves cardiac remodeling and cardiac dysfunction. Allisartan upregulates the expression level of GSTM2 in the hearts of SHRs and significantly affects glutathione metabolism shown by transcriptomics and proteomics analysis. The cardioprotective effect of allisartan may be mediated through activation of the PI3K-AKT-Nrf2 signaling pathway, upregulation of GSTM2 expression, and reduction of SHRs cardiomyocyte apoptosis.

Dataset Information

Quantitative TMT proteomics of brainstem in spontaneously hypertensive rats

Publications

Integrative Metabolic and Proteomic Profiling of the Brainstem in Spontaneously Hypertensive Rats.

Similar Datasets

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