Corynoline protects Ang II-induced hypertensive heart failure by increasing PPARα and inhibiting NF-κB pathway
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA823927 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18653326_1.fastq.gz | Fastqsanger.gz | |||
| SRR18653326_2.fastq.gz | Fastqsanger.gz | |||
| SRR18653327_1.fastq.gz | Fastqsanger.gz | |||
| SRR18653327_2.fastq.gz | Fastqsanger.gz | |||
| SRR18653328_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Heart failure is a fairly common outcome of hypertension. Recent studies have highlighted the key role of the non-hemodynamic activity of angiotensin II (Ang II) in hypertensive heart failure via inducing cardiac inflammation. Drugs that disrupt Ang II-induced cardiac inflammation may have clinical utility in the treatment of hypertensive heart failure. A naturally occurring compound, corynoline, exhibit anti-inflammatory activities in other systems. C57BL/6 mice were injected with Ang II via a micro-osmotic pump for four weeks to develop hypertensive heart failure. The mice were treated with corynoline by gavage for two weeks. RNA-sequencing analysis was performed to explore the potential mechanism of corynoline. We found that corynoline could inhibit inflammation, myocardial fibrosis, and hypertrophy to prevent heart dysfunction, without the alteration of blood pressure. RNA-sequencing analysis indicates that the PPARα pathway is involved Ang II-induced cardiac fibrosis and cardiac remodeling. Corynoline reversed Ang II-induced PPARα inhibition both in vitro and in vivo. We further found that corynoline increases the interaction between PPARα and P65 to inhibit the NF-κB pro-inflammatory pathway in H9c2 cells. Our studies show that corynoline relieves Ang II-induced hypertensive heart failure by increasing the interaction between PPARα and P65 to inhibit the NF-κB pathway.
2022-04-09 | GSE200279 | GEO
Project description:To investigated the therapeutic mechanism underlying the MK-626 improves vascular endothelial functionin hypertension, we performed bioinformatics analyses on the expression profiles of long noncoding RNAs (lncRNAs) and message RNAs (mRNAs) and in the aortae from Ang Ⅱ-induced hypertensive mice with or without MK-626 treatment.
2021-08-11 | GSE165561 | GEO
Project description:The Ca2+/calmodulin-dependent kinase II is expressed in smooth muscle and believed to mediate intracellular calcium handling and calcium-dependent gene transcription. CaMKII is activated by Angiotensin-II. The multifunctional calcium/calmodulin-dependent kinase II (CaMKII) is activated by Angiotensin-II (Ang-II) in vascular smooth muscle cells (VSMC), but its impact on hypertension remains unknown. In our transgenic mice that express the inhibitor peptide CaMKIIN in smooth muscle (TG SM-CaMKIIN), the blood pressure response to chronic Ang-II infusion was significantly reduced as compared to littermate controls. Surprisingly, examination of blood pressure and heart rate under ganglionic blockade revealed a key role for VSMC CaMKII in efferent sympathetic outflow in response to Ang II hypertension. Consistently, the efferent splanchnic nerve activity and plasma phenylephrine concentrations were significantly lower in TG SM-CaMKIIN mice as compared to littermates. Moreover, the aortic depressor nerve activity was reset in hypertensive wild type animals, but not in TG SM-CaMKIIN mice, suggesting that changes in baroreceptor wall activity may be responsible for the blood pressure difference in Ang-II hypertension. The pulse wave velocity, a measure of vascular wall stiffness in vivo, was increased in aortas of hypertensive compared to normotensive WT animals. However, Ang-II infusion did not alter the pulse wave velocity in transgenic mice, suggesting that CaMKII in VSMC controls structural smooth muscle genes. Accordingly, analysis of gene expression changes in aortas from wild type and TG SM-CaMKIIN hypertensive mice demonstrated that CaMKII inhibition mainly altered the expression of muscle contractile proteins. In contrast, TG SM-CaMKIIN aortas were protected from the Ang-II induced upregulation of genes linked to proliferation, suggesting that CaMKII inhibition prevents the Ang-II-induced reprogramming of smooth muscle cell gene expression towards a proliferative phenotype. 5 WT C57Bl/6 and 5 mice that express the Ca2+/calmodulin-dependent kinase II peptide inhibitor CaMKIIN in smooth muscle only (TG SM-CaMKIIN) were infused with 1.25 ug/kg/min Angiotensin-II by osmotic minipump for 14 days. 5 WT and 5 transgenic mice infused with normal saline served as controls. The mice were sacrificed on day 14 and the thoracic aortas isolated. RNA was isolated and pooled for the following groups: WT (wild type), C (TG SM-CaMKIIN), WT-A (WT with Angiotensin-II), C-A (TG SM-CaMKIIN + Angiotensin-II)
2015-07-01 | E-GEOD-64613 | biostudies-arrayexpress
Project description:The Ca2+/calmodulin-dependent kinase II is expressed in smooth muscle and believed to mediate intracellular calcium handling and calcium-dependent gene transcription. CaMKII is activated by Angiotensin-II. The multifunctional calcium/calmodulin-dependent kinase II (CaMKII) is activated by Angiotensin-II (Ang-II) in vascular smooth muscle cells (VSMC), but its impact on hypertension remains unknown. In our transgenic mice that express the inhibitor peptide CaMKIIN in smooth muscle (TG SM-CaMKIIN), the blood pressure response to chronic Ang-II infusion was significantly reduced as compared to littermate controls. Surprisingly, examination of blood pressure and heart rate under ganglionic blockade revealed a key role for VSMC CaMKII in efferent sympathetic outflow in response to Ang II hypertension. Consistently, the efferent splanchnic nerve activity and plasma phenylephrine concentrations were significantly lower in TG SM-CaMKIIN mice as compared to littermates. Moreover, the aortic depressor nerve activity was reset in hypertensive wild type animals, but not in TG SM-CaMKIIN mice, suggesting that changes in baroreceptor wall activity may be responsible for the blood pressure difference in Ang-II hypertension. The pulse wave velocity, a measure of vascular wall stiffness in vivo, was increased in aortas of hypertensive compared to normotensive WT animals. However, Ang-II infusion did not alter the pulse wave velocity in transgenic mice, suggesting that CaMKII in VSMC controls structural smooth muscle genes. Accordingly, analysis of gene expression changes in aortas from wild type and TG SM-CaMKIIN hypertensive mice demonstrated that CaMKII inhibition mainly altered the expression of muscle contractile proteins. In contrast, TG SM-CaMKIIN aortas were protected from the Ang-II induced upregulation of genes linked to proliferation, suggesting that CaMKII inhibition prevents the Ang-II-induced reprogramming of smooth muscle cell gene expression towards a proliferative phenotype.
2015-07-01 | GSE64613 | GEO
Project description:Autophagy is an evolutionally conserved catabolic process that recycles nutrients upon starvation and maintains cellular energy homeostasis1-3. Its acute regulation by nutrient sensing signaling pathways is well described, but its longer-term transcriptional regulation is not. The nuclear receptors PPARα and FXR are activated in the fasted or fed liver, respectively4,5. Here we show that both regulate hepatic autophagy. Pharmacologic activation of PPARα reverses the normal suppression of autophagy in the fed state, inducing autophagic lipid degradation, or lipophagy. This response is lost in PPARα knockout (PPARα-/-) mice, which are partially defective in the induction of autophagy by fasting. Pharmacologic activation of the bile acid receptor FXR strongly suppresses the induction of autophagy in the fasting state, and this response is absent in FXR knockout (FXR-/-) mice, which show a partial defect in suppression of hepatic autophagy in the fed state. PPARα and FXR compete for binding to shared sites in autophagic gene promoters, with opposite transcriptional outputs. These results reveal complementary, interlocking mechanisms for regulation of autophagy by nutrient status. Mouse liver PPARα cistromes in fed 8-week-old male WT or PPARα KO mice treated with or without its synthetic agonist ligand GW7647twice a day were generated by deep sequencing in quadruplicate using illumina
2014-09-27 | E-GEOD-61817 | biostudies-arrayexpress
Project description:To investigated the mechanism underlying the therapeutic effects of berberine in the vasculature in hypertension, we performed systematical analyses on the expression profiles of message RNAs (mRNAs) and long noncoding RNAs (lncRNAs) in the aortae from Ang Ⅱ-induced hypertensive mice with or without berberine treatment.
2021-03-03 | GSE159725 | GEO
Project description:Methylococcus sp. ANG Genome sequencing
| PRJNA1131670 | ENA
Project description:Angiotensin II (Ang II)-mediated vascular smooth muscle cells (VSMC) dysfunction plays a critical role in cardiovascular diseases. However, the gene expression in this process is unclear. We used Rat Affymetrix gene array to profile Ang II-regulated gene in RVSMC and evaluated their role in VSMC dysfunction. Examined 4 samples of Rat VSMC in triplicate. Control (without Ang II treatment) and 3 samples treated with Ang II for 6h, 12h, and 24h. Compared the changes in gene expression in Ang II treated samples relative to control samples.
2012-03-23 | E-GEOD-35627 | biostudies-arrayexpress
Project description:Formyl peptide receptors (FPR) play a critical role in the regulation of resolution of inflammation, an important mediator of hypertension-induced cardiac damage. We have previously discovered an FPR small-molecule prototype Cmpd17b exhibit cardioprotective effects against acute and severe cardiac inflammatory insults, but its impact on chronic cardiac inflammatory insult, such as hypertension, has not been explored. To investigate the therapeutic potential of our FPR agonist on mean arterial pressure (MAP), cardiac remodelling and function in hypertensive mice. This dataset relates to cardiac fibroblasts (human) and smooth muscle aortic cells (SMAC) cell proteome remodelling following Ang-II and Cmp17b treatment
2024-01-24 | MSV000093917 | MassIVE