scholarly journals Age-related autocrine diabetogenic effects of transgenic resistin in spontaneously hypertensive rats: gene expression profile analysis

2011 ◽  
Vol 43 (7) ◽  
pp. 372-379 ◽  
Author(s):  
Michal Pravenec ◽  
Václav Zídek ◽  
Vladimír Landa ◽  
Miroslava Šimáková ◽  
Petr Mlejnek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Intolerance ◽  
Spontaneously Hypertensive Rats ◽  
Metabolic Effects ◽  
Related Factor ◽  
Hypertensive Rats ◽  
Transgenic Rats ◽  
Spontaneously Hypertensive

Increased circulating levels of resistin have been proposed as a possible link between obesity and insulin resistance; however, many of the potential metabolic effects of resistin remain to be investigated, including systemic versus local resistin action. We investigated potential autocrine effects of resistin on lipid and glucose metabolism in 2- and 16-mo-old transgenic spontaneously hypertensive rats (SHR) expressing a nonsecreted form of mouse resistin under control of the aP2 promoter. To search for possible molecular mechanisms, we compared gene expression profiles in adipose tissue in 6-wk-old transgenic SHR versus control rats, before development of insulin resistance, by digital transcriptional profiling using high-throughput sequencing. Both young and old transgenic rats showed moderate expression of the resistin transgene in adipose tissue but had serum resistin levels similar to control SHR and undetectable levels of transgenic resistin in the circulation. Young transgenic rats exhibited mild glucose intolerance. In contrast, older transgenic rats displayed marked glucose intolerance in association with near total resistance of adipose tissue to insulin-stimulated glucose incorporation into lipids (6 ± 2 vs. 77 ± 19 nmol glucose·g−1·2 h−1, P < 0.00001). Ingenuity Pathway Analysis of differentially expressed genes revealed calcium signaling, Nuclear factor-erythroid 2-related factor-2 (NRF2)-mediated oxidative stress response, and actin cytoskeletal signaling canonical pathways as those most significantly affected. Analysis using DAVID software revealed oxidative phosphorylation, glutathione metabolism, pyruvate metabolism, and peroxisome proliferator-activated receptor (PPAR) signaling as top Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. These results suggest that with increasing age autocrine effects of resistin in fat tissue may predispose to diabetes in part by impairing insulin action in adipose tissue.

scholarly journals Candesartan-Induced Gene Expression in Five Organs of Stroke-Prone Spontaneously Hypertensive Rats

2008 ◽  
Vol 31 (10) ◽  
pp. 1963-1975 ◽  
Author(s):  
Norihiro Kato ◽  
Yi-Qiang Liang ◽  
Yoshinori Ochiai ◽  
Naoko Birukawa ◽  
Masakuni Serizawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

scholarly journals System-based DNA microarray analyses of different gene expression profile in spontaneously hypertensive rats treated with Songling Xuemaikang Capsule reveals underlying causal mechanisms.

2019 ◽  
Author(s):  
Li-tao Liu ◽  
Cui-qi Yan ◽  
Qiao-xin Tang ◽  
Man-xi Zhao ◽  
Chuan-zhen Teng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vascular Remodeling ◽  
Spontaneously Hypertensive Rats ◽  
Control Group ◽  
Causal Network ◽  
Ang Ii ◽  
Dosage Group ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Songling Xuemaikang Capsule

Abstract Background: Hypertension is considered the major risk factor for human health in the world. Songling Xuemaikang Capsule (SXC) is clinically used as a medicine for the prevention and treatment of cardiovascular and cerebrovascular diseases such as hypertension and hyperlipidemia. However, the underlying mechanisms have yet to be fully identified. Methods: Valsartan, as a positive control drug, high- and low-dose of SXC were orally administration with for 28 days to investigate the anti-hypertensive effect of SXC in spontaneously hypertensive rats (SHRs). The serum levels of aldosterone and Angiotensin II (Ang II) were detected. The gene expression profiling was performed in the thoracic aorta of SHRs using the Whole Rat Genome Oligo nucleotide Microarray. The integrated causal network analysis was performed to understand the mechanism of antihypertensive effect of SXC. Results: The results shown that the systolic and diastolic blood pressure were significant decreased in SXC low-dosage group and high-dosage group compared with the control group respectively. SXC low and high-dosage treatment decreased serum aldosterone levels significantly but increased serum Ang II compared with the control group respectively. Causal network analysis shown that treatment with SXC reversing the vascular remodeling process, inhibiting vascular inflammation and atherosclerosis, reversing endothelial cells dysfunction and likely reducing peripheral vascular resistance by down-regulated processes related to vascular remodeling, dyslipidemia, the complement system, leukocyte rolling, and endothelial dysfunction. In addition, SXC treatment may also activate fibrinolysis and regulate lipid and glucose metabolism. Conclusions: Those obtained data could help our understanding and potential utilization of SXC in the treatment or prevention of hypertension。

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