Discovery of Side- and Shear-Dependent miRNAs and mRNAs in Human Aortic Valvular Endothelial Cells

2011 ◽  
Author(s):  
Casey J. Holliday ◽  
Randall F. Ankeny ◽  
Hanjoong Jo ◽  
Robert M. Nerem
Keyword(s):  
Endothelial Cells ◽  
Aortic Valve ◽  
Oscillatory Flow ◽  
Expression Profiles ◽  
Flow Conditions ◽  
Expression Of Genes ◽  
Inflammatory Phenotype ◽  
Cardiovascular Pathologies ◽  
Laminar Shear

Aortic valve (AV) disease is diagnosed by severe symptoms, such as calcification, and typically treated by AV replacement and repair surgeries. The mechanism by which AV disease occurs, specifically the role of the endothelium remains relatively unknown. It is known that disease preferentially occurs on the fibrosa, or aortic side, where it is exposed to disturbed, oscillatory flow, whereas the ventricularis, or side facing the left ventricle, experiences pulsatile, laminar shear and remains non-calcified [1, 2]. Research shows that regulation of miRNAs, short nucleotide segments targeting mRNAs, coincides with cardiovascular pathologies [3] though expression profiles of miRNAs and the mRNAs they modulate in human AV endothelial cells (HAVECs) have not been reported. We hypothesize that disturbed flow conditions present on the fibrosa stimulate ECs to modify expression of genes and miRNAs to induce a pro-inflammatory phenotype.

scholarly journals Discovery of shear- and side-specific mRNAs and miRNAs in human aortic valvular endothelial cells

2011 ◽  
Vol 301 (3) ◽  
pp. H856-H867 ◽  
Author(s):  
Casey J. Holliday ◽  
Randall F. Ankeny ◽  
Hanjoong Jo ◽  
Robert M. Nerem
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Aortic Valve ◽  
Pathway Analysis ◽  
Array Analysis ◽  
Mirna Array ◽  
Specific Mrnas ◽  
Mrna Microarray ◽  
Laminar Shear

The role of endothelial cells (ECs) in aortic valve (AV) disease remains relatively unknown; however, disease preferentially occurs in the fibrosa. We hypothesized oscillatory shear (OS) present on the fibrosa stimulates ECs to modify mRNAs and microRNAs (miRNAs) inducing disease. Our goal was to identify mRNAs and miRNAs differentially regulated by OS and laminar shear (LS) in human AVECs (HAVECs) from the fibrosa (fHAVECs) and ventricularis (vHAVECs). HAVECs expressed EC markers as well as some smooth muscle cell markers and functionally aligned with the flow. HAVECs were exposed to OS and LS for 24 h, and total RNA was analyzed by mRNA and miRNA microarrays. We found over 700 and 300 mRNAs down- and upregulated, respectively, by OS; however, there was no side dependency. mRNA microarray results were validated for 26 of 28 tested genes. Ingenuity Pathway Analysis revealed thrombospondin 1 ( Thbs1) and NF-κB inhibitor-α ( Nfkbia) as highly connected, shear-sensitive genes. miRNA array analysis yielded 30 shear-sensitive miRNAs and 3 side-specific miRNAs. miRNA validation confirmed 4 of 17 shear-sensitive miRNAs and 1 of 3 side-dependent miRNAs. Using miRWalk and several filtering steps, we identified shear-sensitive mRNAs potentially targeted by shear-sensitive miRNAs. These genes and signaling pathways could act as therapeutic targets of AV disease.

scholarly journals Role of agr (RNAIII) in Staphylococcus aureus adherence to fibrinogen, fibronectin, platelets and endothelial cells under static and flow conditions

2002 ◽  
Vol 51 (9) ◽  
pp. 747-754 ◽  
Author(s):  
BORIS SHENKMAN ◽  
DAVID VARON ◽  
ILIA TAMARIN ◽  
RIMA DARDIK ◽  
MARTHA PEISACHOV ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Endothelial Cells ◽  
Flow Conditions

Abstract 570: Cystathionine γ-Lyase Modulates Flow-dependent Vascular Remodeling

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Shuai Yuan ◽  
Arif Yurdagul ◽  
Jonette M Green ◽  
Sibile Pardue ◽  
Christopher G Kevil ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Remodeling ◽  
Oscillatory Flow ◽  
Carotid Arteries ◽  
Dependent Manner ◽  
Disturbed Flow ◽  
Sulfane Sulfur ◽  
Nitrite Level

Disturbed flow causes endothelial dysfunction and development of atherosclerotic lesions. The gaseous signaling molecule H 2 S and cystathionine γ-lyase (CSE), its major enzymatic source in the vasculature, protect against cardiovascular diseases including atherosclerosis, peripheral artery disease, and cardiac ischemia in a nitric oxide (NO) dependent manner. Therefore, we sought to investigate the role of CSE in the endothelial response to disturbed flow. Wild-type C57Bl/6 (WT) and CSE knockout (CSE-/-) mice underwent partial carotid ligation to induce disturbed flow in the left carotid with the right carotid serving as an internal control. Additionally, endothelial cells isolated from WT and CSE-/- mice were exposed to oscillatory flow, a model of disturbed flow, in vitro. While disturbed flow decreased endothelial CSE mRNA expression, CSE protein expression showed strong induction under disturbed flow conditions both in vitro and in vivo. This induction correlated with enhanced free sulfide and sulfane sulfur production in WT but not in CSE-/- mice. Intimal mRNA isolated 2 days post-ligation showed increased VCAM-1 and ICAM-1 expression in WT mice which was prevented in CSE-/- mice. Similarly, endothelial cells isolated from CSE-/- mice show reduced NF-B activation and proinflammatory gene expression in response to oscillatory flow in vitro. Morphometric analysis of carotid arteries collected 7 days post-ligation revealed reduced macrophage infiltration and medial thickening in the ligated carotid of CSE-/- mice. Interestingly, ligation increased the carotid nitrite level in WT mice but not in CSE-/- mice. However, nitrite level of the non-ligated carotid was significantly higher in the CSE-/- mice compared to WT mice. Shear induced phosphorylation of eNOS Ser1179 in vitro was not different between WT and CSE knockout endothelial cells, suggesting alternative regulatory mechanisms. Collectively, CSE in mouse carotid arteries plays a critical role in flow dependent vascular remodeling, which may be mediated by CSE derived free sulfide and sulfane sulfur. CSE deficiency completely inhibits disturbed flow-induced NF-κB activation and macrophage recruitment, consistent with the role of inflammation in vascular remodeling.

scholarly journals High Glucose Activates YAP Signaling to Promote Vascular Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jeremy Ortillon ◽  
Jean-Christophe Le Bail ◽  
Elise Villard ◽  
Bertrand Léger ◽  
Bruno Poirier ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
High Glucose ◽  
Oscillatory Flow ◽  
Vascular Inflammation ◽  
Vascular Complications ◽  
Diabetic Mice ◽  
Flow Conditions ◽  
Endothelial Inflammation

Background and AimsThe YAP/TAZ signaling is known to regulate endothelial activation and vascular inflammation in response to shear stress. Moreover, YAP/TAZ signaling plays a role in the progression of cancers and renal damage associated with diabetes. However, whether YAP/TAZ signaling is also implicated in diabetes-associated vascular complications is not known.MethodsThe effect of high glucose on YAP/TAZ signaling was firstly evaluated in vitro on endothelial cells cultured under static conditions or subjected to shear stress (either laminar or oscillatory flow). The impact of diabetes on YAP/TAZ signaling was additionally assessed in vivo in db/db mice.ResultsIn vitro, we found that YAP was dephosphorylated/activated by high glucose in endothelial cells, thus leading to increased endothelial inflammation and monocyte attachment. Moreover, YAP was further activated when high glucose was combined to laminar flow conditions. YAP was also activated by oscillatory flow conditions but, in contrast, high glucose did not exert any additional effect. Interestingly, inhibition of YAP reduced endothelial inflammation and monocyte attachment. Finally, we found that YAP is also activated in the vascular wall of diabetic mice, where inflammatory markers are also increased.ConclusionWith the current study we demonstrated that YAP signaling is activated by high glucose in endothelial cells in vitro and in the vasculature of diabetic mice, and we pinpointed YAP as a regulator of high glucose-mediated endothelial inflammation and monocyte attachment. YAP inhibition may represent a potential therapeutic opportunity to improve diabetes-associated vascular complications.

scholarly journals The Evolution and Expression Profiles of EC1 Gene Family during Development in Cotton

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 2001
Author(s):  
Xinyu Wang ◽  
Wei Chen ◽  
Jinbo Yao ◽  
Yan Li ◽  
Akwasi Yeboah ◽  
...  
Keyword(s):  
Gene Family ◽  
Plant Species ◽  
Potential Role ◽  
Expression Profiles ◽  
Gene Interaction ◽  
Pcr Analysis ◽  
Egg Cell ◽  
Gene Interaction Networks ◽  
Expression Of Genes

Fertilization is essential to sexual reproduction of flowering plants. EC1 (EGG CELL 1) proteins have a conserved cysteine spacer characteristic and play a crucial role in double fertilization process in many plant species. However, to date, the role of EC1 gene family in cotton is fully unknown. Hence, detailed bioinformatics analysis was explored to elucidate the biological mechanisms of EC1 gene family in cotton. In this study, we identified 66 genes in 10 plant species in which a total of 39 EC1 genes were detected from cotton genome. Phylogenetic analysis clustered the identified EC1 genes into three families (I-III) and all of them contain Prolamin-like domains. A good collinearity was observed in the synteny analysis of the orthologs from cotton genomes. Whole-genome duplication was determined to be one of the major impetuses for the expansion of the EC1 gene family during the process of evolution. qRT-PCR analysis showed that EC1 genes were highly expressed in reproductive tissues under multiple stresses, signifying their potential role in enhancing stress tolerance or responses. Additionally, gene interaction networks showed that EC1 genes may be involved in cell stress and response transcriptional regulator in the synergid cells and activate the expression of genes required for pollen tube guidance. Our results provide novel functional insights into the evolution and functional elucidation of EC1 gene family in cotton.

scholarly journals Biology of Intracranial Aneurysms: Role of Inflammation

2012 ◽  
Vol 32 (9) ◽  
pp. 1659-1676 ◽  
Author(s):  
Nohra Chalouhi ◽  
Muhammad S Ali ◽  
Pascal M Jabbour ◽  
Stavropoula I Tjoumakaris ◽  
L Fernando Gonzalez ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Intracranial Aneurysms ◽  
Clinical Problem ◽  
Vascular Wall ◽  
Expression Of Genes ◽  
Aneurysmal Dilation ◽  
Inflammatory Phenotype ◽  
Aneurysm Development ◽  
Precise Role

Intracranial aneurysms (IAs) linger as a potentially devastating clinical problem. Despite intense investigation, our understanding of the mechanisms leading to aneurysm development, progression and rupture remain incompletely defined. An accumulating body of evidence implicates inflammation as a critical contributor to aneurysm pathogenesis. Intracranial aneurysm formation and progression appear to result from endothelial dysfunction, a mounting inflammatory response, and vascular smooth muscle cell phenotypic modulation producing a pro-inflammatory phenotype. A later final common pathway appears to involve apoptosis of cellular constituents of the vessel wall. These changes result in degradation of the integrity of the vascular wall leading to aneurysmal dilation, progression and eventual rupture in certain aneurysms. Various aspects of the inflammatory response have been investigated as contributors to IA pathogenesis including leukocytes, complement, immunoglobulins, cytokines, and other humoral mediators. Furthermore, gene expression profiling of IA compared with control arteries has prominently featured differential expression of genes involved with immune response/inflammation. Preliminary data suggest that therapies targeting the inflammatory response may have efficacy in the future treatment of IA. Further investigation, however, is necessary to elucidate the precise role of inflammation in IA pathogenesis, which can be exploited to improve the prognosis of patients harboring IA.

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