RESUMO
BACKGROUNDS: Long noncoding RNAs (lncRNAs) play an important role in various biological processes. However, their functions in salt-sensitive hypertension are largely unknown. In this study, the lncRNA-seq technique was employed to compare the expression profiles of lncRNAs and mRNAs in salt-sensitive hypertensive rats. METHODS: Blood pressure, serum sodium, and urinary creatinine were texted in salt-sensitive and salt-insensitive rats fed with different salt concentrations. High-throughput sequencing was used to detect the expression of lncRNAs and mRNA in the renal medulla of the two groups. RESULTS: Blood pressure and urinary sodium/creatinine of high-salt diets of the sensitive group were significantly higher than that in the control group. Serum sodium has no significant difference between the two groups in high-salt diets. NONRATG007131.2 and NONRATG012674.2 were the most different lncRNAs in the high salt-sensitive group. Correlation analysis reveals that Matn1, Serpinb12, Anxa8, and Hspa5 may play an important role in salt-sensitive hypertension. CONCLUSION: This study analyzed the difference in lncRNA and mRNA between salt-sensitive and salt-insensitive rats with different salt diets by high-throughput sequencing. Salt sensitivity and salt concentration were two key factors for the induction of hypertension. We found some potential genes that play an important role in salt-sensitive hypertension.
Assuntos
Hipertensão/genética , RNA Longo não Codificante/genética , Transcriptoma/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Chaperona BiP do Retículo Endoplasmático , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hipertensão/sangue , Hipertensão/patologia , Hipertensão/urina , RNA Longo não Codificante/isolamento & purificação , Ratos , Ratos Endogâmicos Dahl/sangue , Ratos Endogâmicos Dahl/genética , Cloreto de Sódio/sangue , Cloreto de Sódio/urina , Cloreto de Sódio na Dieta/farmacologia , Sequenciamento do ExomaRESUMO
Salt-sensitive hypertension is a major risk factor for cardiovascular disorders. Our previous proteomic study revealed substantial differences in several proteins between Dahl salt-sensitive (SS) rats and salt-insensitive consomic SS.13(BN) rats. Subsequent experiments indicated a role of fumarase insufficiency in the development of hypertension in SS rats. In the present study, a global metabolic profiling study was performed using gas chromatography/mass spectrometry (GC/MS) in plasma of SS rats (n=9) and SS.13(BN) rats (n=8) on 0.4% NaCl diet, designed to gain further insights into the relationship between alterations in cellular intermediary metabolism and predisposition to hypertension. Principal component analysis of the data sets revealed a clear clustering and separation of metabolic profiles between SS rats and SS.13(BN) rats. 23 differential metabolites were identified (P<0.05). Higher levels of five TCA cycle metabolites, fumarate, cis-aconitate, isocitrate, citrate and succinate, were observed in SS rats. Pyruvate, which connects TCA cycle and glycolysis, was also increased in SS rats. Moreover, lower activity levels of fumarase, aconitase, α-ketoglutarate dehydrogenase and succinyl-CoA synthetase were detected in the heart, liver or skeletal muscles of SS rats. The distinct metabolic features in SS and SS.13(BN) rats indicate abnormalities of TCA cycle in SS rats, which may play a role in predisposing SS rats to developing salt-sensitive hypertension.
Assuntos
Proteínas Sanguíneas/metabolismo , Hipertensão/sangue , Proteoma/metabolismo , Ratos Endogâmicos BN/sangue , Ratos Endogâmicos Dahl/sangue , Cloreto de Sódio na Dieta/sangue , Animais , Pressão Sanguínea/genética , Predisposição Genética para Doença/genética , Hipertensão/genética , Endogamia , Ratos , Ratos Endogâmicos BN/genética , Ratos Endogâmicos Dahl/genética , Tolerância ao Sal/genéticaRESUMO
Plasma 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) concentration was shown to decrease during bed rest in several studies when baseline plasma 25-hydroxyvitamin D (25-OHD) concentration was sub-optimal. Dahl salt-sensitive female (S) rats, but not Dahl salt-resistant female (R) rats, demonstrated a 50% decrease in plasma 1,25-dihydroxycholecalciferol (1,25-(OH)(2)D(3)) concentration after 28 days of hind limb unloading (HU, disuse model) during low salt intake (0.3%). We tested the vitamin D endocrine system response of female S rats to hind limb unloading during high salt intake (2%, twice that of standard rat chow to mimic salt intake in the USA). Hind limb unloading resulted in lower plasma 25-OHD(3) concentrations in S-HU rats than in R-HU rats (P<0.05) and greater urinary loss of 25-OHD(3) by S-HU rats than by S rats (P<0.05). Plasma 1,25-(OH)(2)D(3) concentration of S-HU rats was half that of S rats, but was unchanged in R-HU rats. The association of low plasma 25-OHD concentration with decrease in plasma 1,25-(OH)(2)D concentration of hind limb unloaded rats and of bed rest participants (published studies) suggests that low vitamin D status might be a risk factor for decrease in plasma vitamin D hormone concentration during long-term immobilization or bed rest.