RNA-Seq transcriptomic landscape profiling of spontaneously hypertensive rats treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor

Tan, Fangyan; Long, Xianglin; Du, Jianlin; Yuan, Xin

doi:10.1016/j.biopha.2023.115289

Cited by 3 publications

(2 citation statements)

References 55 publications

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“…This dataset includes transcriptome expression profiles of multiple tissues from SHR rats treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin. Although HTN is not an indication for engeletin, the treatment remained effective ( 56 ). Throughout the blood pressure-lowering course, there was a tendency for Spp1, Postn, and Gpnmb to decrease in visceral white adipose tissue, with insignificant changes in Col4a2.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms and potential therapeutic targets in the pathogenesis of hypertension in visceral adipose tissue induced by a high-fat diet

Su,

Sun,

Gao

et al. 2024

Front. Cardiovasc. Med.

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BackgroundHypertension (HTN) presents a significant global public health challenge with diverse causative factors. The accumulation of visceral adipose tissue (VAT) due to a high-fat diet (HFD) is an independent risk factor for HTN. While various studies have explored pathogenic mechanisms, a comprehensive understanding of impact of VAT on blood pressure necessitates bioinformatics analysis.MethodsDatasets GSE214618 and GSE188336 were acquired from the Gene Expression Omnibus and analyzed to identify shared differentially expressed genes between HFD-VAT and HTN-VAT. Gene Ontology enrichment and protein-protein interaction analyses were conducted, leading to the identification of hub genes. We performed molecular validation of hub genes using RT-qPCR, Western-blotting and immunofluorescence staining. Furthermore, immune infiltration analysis using CIBERSORTx was performed.ResultsThis study indicated that the predominant characteristic of VAT in HTN was related to energy metabolism. The red functional module was enriched in pathways associated with mitochondrial oxidative respiration and ATP metabolism processes. Spp1, Postn, and Gpnmb in VAT were identified as hub genes on the pathogenic mechanism of HTN. Proteins encoded by these hub genes were closely associated with the target organs-specifically, the resistance artery, aorta, and heart tissue. After treatment with empagliflozin, there was a tendency for Spp1, Postn, and Gpnmb to decrease in VAT. Immune infiltration analysis confirmed that inflammation and immune response may not be the main mechanisms by which visceral adiposity contributes to HTN.ConclusionsOur study pinpointed the crucial causative factor of HTN in VAT following HFD. Spp1, Postn, and Gpnmb in VAT acted as hub genes that promote elevated blood pressure and can be targets for HTN treatment. These findings contributed to therapeutic strategies and prognostic markers for HTN.

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Section: Discussionmentioning

confidence: 99%

Molecular mechanisms and potential therapeutic targets in the pathogenesis of hypertension in visceral adipose tissue induced by a high-fat diet

Su,

Sun,

Gao

et al. 2024

Front. Cardiovasc. Med.

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“… 99 Moreover, in spontaneously hypertensive rats, continuous feeding of empagliflozin for 30 days improved inflammatory response and blood pressure. 100 Dapagliflozin pretreatment of macrophages obtained from healthy humans reduced M1 polarisation by bacterial lipopolysaccharide in vitro, thus reducing the M1/M2 ratio and blocking pro-inflammatory factor secretion. 101 Additionally, in C57BL/6 mice with lipopolysaccharide-induced lung injury, canagliflozin reduced the M1/M2 macrophage ratio in vivo and contributed to attenuating the inflammatory response.…”

Section: Obesity-associated Hypertension Sglt-2 Inhibitors and Inflam...mentioning

confidence: 99%

Sodium–Glucose Cotransporter Protein 2 Inhibitors: Novel Application for the Treatment of Obesity-Associated Hypertension

Hu,

Bao,

Gao

et al. 2024

DMSO

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Obesity is becoming increasingly prevalent in China and worldwide and is closely related to the development of hypertension. The pathophysiology of obesity-associated hypertension is complex, including an overactive sympathetic nervous system (SNS), activation of the renin–angiotensin–aldosterone system (RAAS), insulin resistance, hyperleptinemia, renal dysfunction, inflammatory responses, and endothelial function, which complicates treatment. Sodium–glucose cotransporter protein 2 (SGLT-2) inhibitors, novel hypoglycemic agents, have been shown to reduce body weight and blood pressure and may serve as potential novel agents for the treatment of obesity-associated hypertension. This review discusses the beneficial mechanisms of SGLT-2 inhibitors for the treatment of obesity-associated hypertension. SGLT-2 inhibitors can inhibit SNS activity, reduce RAAS activation, ameliorate insulin resistance, reduce leptin secretion, improve renal function, and inhibit inflammatory responses. SGLT-2 inhibitors can, therefore, simultaneously target multiple mechanisms of obesity-associated hypertension and may serve as an effective treatment for obesity-associated hypertension.

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Hepatoprotective and cardioprotective effects of empagliflozin in spontaneously hypertensive rats fed a high-fat diet

Hojná,

Malínská,

Hüttl

et al. 2024

Biomedicine & Pharmacotherapy

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RNA-Seq transcriptomic landscape profiling of spontaneously hypertensive rats treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor

Cited by 3 publications

References 55 publications

Molecular mechanisms and potential therapeutic targets in the pathogenesis of hypertension in visceral adipose tissue induced by a high-fat diet

Molecular mechanisms and potential therapeutic targets in the pathogenesis of hypertension in visceral adipose tissue induced by a high-fat diet

Sodium–Glucose Cotransporter Protein 2 Inhibitors: Novel Application for the Treatment of Obesity-Associated Hypertension

Hepatoprotective and cardioprotective effects of empagliflozin in spontaneously hypertensive rats fed a high-fat diet

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