Analysis of age-related vascular gene expression in mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE50833 | GEO | 2014/01/14
SECONDARY ACCESSION(S): PRJNA219125
REPOSITORIES: GEO
Similar Datasets
Project description:Analyses of the age-related changes that occur at a gene expression level and transcriptional profile have not been elucidated in depth. To determine the changes of the vascular transcriptome, we conducted gene expression microarray experiments on aortas of adult and old mice, in which age-related vascular dysfunction was confirmed by increased stiffness and associated systolic hypertension C57BL/6 mice obtained from Janvier (Saint Berthevin, France) were aged 6 months (n=6) and 20 (n=6) months and water and standard rodent chow were fed ad libitum. Briefly, the vessel was flushed thoroughly with ice-cold phosphate-buffered saline (PBS), through the left ventricle of the heart, cleaned of periadventitial fat and connective tissues, and snap-frozen in liquid nitrogen and stored at -80 °C.
2014-01-14 | E-GEOD-50833 | biostudies-arrayexpress
Project description:Analyses of the vascular changes that occur following a chronic nitrate supplementation in old mice at a gene expression level and transcriptional profile have not been elucidated in depth. To determine the changes of the vascular transcriptome, we conducted gene expression microarray experiments on aortas of old and old nitrate treated mice, in which age-related vascular dysfunction was confirmed by endothelial dysfunction.
2015-03-16 | GSE66572 | GEO
Project description:B-cell leukemia 11b (BCL11B) is a transcription factor known as an essential regulator of T lymphocytes and neuronal development during embryogenesis. A genome-wide association study (GWAS) showed that a gene desert region downstream of BCL11B, known to function as a BCL11B enhancer, harbors single nucleotide polymorphisms (SNPs) associated with increased arterial stiffness. However, a role for BCL11B in the adult cardiovascular system is unknown. Based on these human findings, we sought to examine the relation between BCL11B and arterial function. Here we report that BCL11B is expressed in the vascular smooth muscle (VSM) where it regulates vascular stiffness. RNA sequencing of aortas from WT and Bcl11b null mice (BSMKO) identified the cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) as the most significant differentially regulated signaling pathway in BSMKO compared to WT mice. BSMKO aortas showed decreased levels of PKG1, increased levels of Ca++-calmodulin-dependent serine/threonine phosphatase calcineurin (PP2B) and their common phosphorylation target, vasodilator-stimulated phosphoprotein (pVASPS239), a regulator of cytoskeletal actin rearrangements. Decreased pVASPS239 in BSMKO aortas was associated with increased actin polymerization (F/G actin ratio). Functionally, aortic force, stress, wall tension and stiffness, measured ex vivo in organ baths, were increased in BSMKO aortas, and BSMKO mice had increased pulse wave velocity, the in vivo index of arterial stiffness. Despite having no effect on blood pressure or microalbuminuria, increased arterial stiffness in BSMKO mice was associated with increased incidence of cerebral microbleeds compared to age-matched WT littermates. In conclusion, we have identified VSM BCL11B as a crucial regulator of aortic smooth muscle function and a potential therapeutic target for vascular stiffness.
2021-12-01 | GSE163551 | 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:Long non-coding RNAs (LncRNAs) in hypertensives and their mechanisms in regulating blood pressure still remain unexplored. The aim of present study is to construct the profiles of LncRNAs in blood of patients with essential hypertension and healthy controls. Methods and results, LncRNA microarray identified up-regulated, anddown-regulated LncRNAs, in hypertensives compared to their healthy controls. Among them, one vascular smooth muscle (VSM)-specific LncRNA AK096656 (LncVSM) was quantitated in plasma of patients with hypertension and their healthy controls using the real-time qRT-PCR. LncVSM shows specific expression in human arterial vascular smooth muscle cells (HASMCs) and promote its proliferation and migration. Expression profiles and Ingenuity Pathway Analysis (IPA) revealed that LncVSM activated Renin-Angiotensin Signaling (RAS). the overexpression of LncVSM would result hypertension related complications. LncVSM (AK098656) transfection
2015-12-12 | E-GEOD-75940 | biostudies-arrayexpress
Project description:<p>Arterial stiffening is a hallmark of early vascular aging (EVA) syndrome and an independent predictor of cardiovascular morbidity and mortality. In this case-control study we sought to identify plasma metabolites associated with EVA syndrome in the setting of hypertension. An untargeted metabolomic approach was used to identify plasma metabolites in an age-, BMI- and sex-matched groups of EVA (n = 79) and non-EVA (n = 73) individuals with hypertension. After raw data processing and filtration, 497 putative compounds were characterized, out of which 4 were identified as lysophosphaditylcholines (LPCs) [LPC (18:2), LPC (16:0), LPC (18:0) and LPC (18:1)]. A main finding of this study shows that identified LPCs were independently associated with EVA status. Although LPCs have been shown previously to be positively associated with inflammation and atherosclerosis, we observed that hypertensive individuals characterized by 4 down-regulated LPCs had 3.8 times higher risk of EVA compared to those with higher LPC levels (OR = 3.8, 95% CI 1.7 – 8.5, P < .001). Our results provide new insights into a metabolomic phenotype of vascular aging and warrants further investigation of negative association of LPCs with EVA status. This study suggests that LPCs are potential candidates to be considered for further evaluation and validation as predictors of EVA in patients with hypertension </p>
2020-01-14 | MTBLS1359 | MetaboLights
Project description:Novel genetic pathways associated with successful and/or unsuccessful vascular aging Customized therapies for vascular disease will require matching the vessel type and genetic background of the patient. Our previous studies showed that progressive age-related vascular pathology is strain specific in the thoracic aorta (TA) and mesenteric arteries (MA) of the Brown Norway (BN) and the Fisher344/Brown Norway F1 hybrid (F1) rats. The purpose of this study was to identify novel genetic pathways associated with successful and/or unsuccessful vascular aging. TA and MA were collected from anesthetized 6, 15 and 24 month old age-matched F1 and BN rats for total RNA isolation. The gene microarrays were generated using the Affimetrix GeneChip Rat Expression 230A Array. Gene expression data was analyzed with the Ingenuity Pathway Analysis and proprietary software. Despite more pronounced age-related vascular pathology in the F1 strain, more genes were differentially expressed in the BN strain during aging. A sample of common key genes (KLB1, TRIO, HLA-C and PCP4) showed similar expression at 6 and 15 months and downregulation at 24 months in F1 vs. upregulation in BN rats. Among the top 50 canonical pathways there was only a 10 and 30% overlap, respectively, between the F1 and BN strains in MA and TA. Most of the overexpressed molecules associated with the same vascular-related biological functions are different between strains. The data suggest that age-related vascular pathology and decrement in function is both strain and vessel-dependent and different genetic programs could be employed to accomplish both normal and pathological physiological processes in conduit and resistance arteries. two strains: two vessel types, 3 different ages
2015-03-02 | E-GEOD-55612 | biostudies-arrayexpress
Project description:Effect of age on the vascular proteome in middle cerebral arteries and small mesenteric arteries in mice
2022-02-09 | PXD024070 | JPOST Repository
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:Investigate the effect of recombinant human IL-17A on vascular smooth muscle cells cultured from human aortas. Keywords: Dose response
2008-06-28 | GSE11367 | GEO