Regulation of Vascular Smooth Muscle Phenotype by Notch Signaling - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Regulation of Vascular Smooth Muscle Phenotype by Notch Signaling write by Joshua Boucher. This book was released on 2014-12-13. Regulation of Vascular Smooth Muscle Phenotype by Notch Signaling available in PDF, EPUB and Kindle. Vascular smooth muscle cells (VSMC) populate the medial layer of blood vessels and are able to modulate their phenotype in response to environmental cues. Defining the molecular pathways that influence the phenotypic state of VSMC is important for understanding cardiovascular development, vascular repair of injury and numerous vascular pathologies. Notch receptors are expressed throughout the lifecycle of VSMC and contribute to their differentiation and proliferation. Activation of Notch receptors by the ligand Jagged-1 (Jag-1) is believed to be a pro-differentiation signal for VSMC; however, the mechanisms downstream of Notch signaling influencing the phenotypic state of VSMC are not defined. I sought to identify novel gene targets of Jag-1/Notch signaling that promote VSMC differentiation, and to define potential non-overlapping functions of Notch receptors in regulating these genes. I observed decreased proliferation and increased contraction upon activation of Notch signaling by Jag-1 in human aortic VSMC. Using microRNA (miR) arrays, I identified miR-143 and miR-145 (miR-143/145) as enriched by Notch signaling and is required for Notch-induced VSMC differentiation in vitro.
Endothelial Cell-dependent Notch Signaling Regulates Vascular Smooth Muscle Cell Phenotypes
Endothelial Cell-dependent Notch Signaling Regulates Vascular Smooth Muscle Cell Phenotypes - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Endothelial Cell-dependent Notch Signaling Regulates Vascular Smooth Muscle Cell Phenotypes write by Cho-Hao Lin. This book was released on 2015. Endothelial Cell-dependent Notch Signaling Regulates Vascular Smooth Muscle Cell Phenotypes available in PDF, EPUB and Kindle. Endothelial cell-dependent Notch signaling plays many critical roles in homeostasis and remodeling in the vasculature and serves an important role in the communication between endothelial cells and mural cells, including vascular smooth muscle cells (SMCs), pericytes, and fibroblasts. Our lab previously showed that endothelial cells govern SMC function and promote smooth muscle differentiation. Endothelial cells are able to induce smooth muscle cells into a mature contractile phenotype through cell contact and Notch signaling. Furthermore, Notch signaling has been shown to regulate SMC-specific gene and miR-143/145 expression to govern SMC differentiation. In this study, I demonstrated that endothelial cell-dependent Notch signaling enhances both contractile and synthetic phenotypes in smooth muscle cells, suggesting endothelial cells not only increase the contractile ability of smooth muscle cells, but might also signal to smooth muscle cells to build the basement membrane and form a functional blood vessel. My data indicate that the Notch2 receptor has a unique function in the regulation of SMC proliferation, and the Notch3 receptor has a distinct role in the regulation of synthetic phenotypes in smooth muscle cells.
The Roles of the Notch2 and Notch3 Receptors in Vascular Smooth Muscle Cells
The Roles of the Notch2 and Notch3 Receptors in Vascular Smooth Muscle Cells - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook The Roles of the Notch2 and Notch3 Receptors in Vascular Smooth Muscle Cells write by Jeremy Todd Baeten. This book was released on 2016. The Roles of the Notch2 and Notch3 Receptors in Vascular Smooth Muscle Cells available in PDF, EPUB and Kindle. The Notch signaling pathway has long been intricately linked with the development and function of the vasculature. In vascular smooth muscle cells (VSMCs), Notch signaling has a great influence on phenotype and is a strong promoter of differentiation and expression of contractile genes necessary to produce a functional vessel wall. However, the role of Notch signaling in VSMC proliferation and survival is less well defined, and some cases contradictory reports are given. Also, the contributions of each individual Notch receptor have not been clearly described. Thus, to better understand Notch signaling in VSMC phenotype, we investigated the specific roles of the predominant Notch receptors in VSMCs as they relate to differentiation, proliferation, and survival. We found that Notch3 promotes Platelet-Derived Growth Factor (PDGF)-induced proliferation in VSMCs, while Notch2 inhibits it. We also found that Notch3 was able to promote cell survival in response to apoptosis cues, while Notch2 had no discernible effect. Interestingly, we also found the expression of Notch2 and Notch3 were changed in response to proliferation and apoptosis inducers. Notch2 mRNA was significantly decreased after PDGF-BB treatment, a proliferation inducer, and Notch3 protein was degraded rapidly in response to induction of apoptosis. Additionally, we demonstrated that Notch3’s induction of cell survival genes required MEK/ERK signaling and Notch3 was capable of increasing levels of phosphorylated ERK. Altogether, these findings demonstrate that Notch2 and Notch3 have unique functions in regulating VSMC phenotype. In a mouse model devoid of Notch2 and Notch3 in smooth muscle cells, we were able to show that Notch2 and Notch3 are required for normal closure of the ductus arteriosus. Animals without Notch2 in VSMCs presented with patent ductus arteriosus with increasing incidence combined with the loss of Notch3. These mice died within one day of birth and also presented with aortic dilation. These phenotypes wee correlated with a significant loss of the smooth muscle contractile genes MYH11 and ACTA2, and it has been previously reported that defects in contractile differentiation can produce the PDA phenotype. This suggests that the Notch2 and Notch3 share an overlapping role in promoting VSMC differentiation. The Notch-regulated microRNA 145 has been strongly implicated in VSMC differentiation and also recently shown to regulate cardiovascular fibrosis. In order to better understand these connections to differentiation and fibrosis, we created and characterized a transgenic mouse for conditional expression of miR145, miR145TG. We were able to select a line that faithfully expresses the transgene and produces mature miR145 transcript. This model will allow for further investigation into miR145’s roles in promoting VSMC differentiation and mediating fibrosis.
Sirolimus-Eluting Stents
Sirolimus-Eluting Stents - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Sirolimus-Eluting Stents write by Patrick W. Serruys. This book was released on 2004-11-29. Sirolimus-Eluting Stents available in PDF, EPUB and Kindle. Recently, sirolimus-eluting stents implantation has been shown to decrease restenosis markedly in selected patients. Nonetheless, the effects of SES implantation in complex, unselected patients, such as those commonly treated in daily practice ('the real world'), remains largely unknown. This book comprehensively evaluates the impact of SES implantation on the outcomes of patients treated in the real world of interventional cardiology. The authors have evaluated in detail the short- and long-term outcomes of several high-risk subsets not currently included in randomized trials. While it is specific to sirolimus, the book covers the major competing drug eluting stents, including paclitaxel.
The Implication of Adenylyl Cyclase Isoform 8 and Its Regulation by the Notch Pathway in Vascular Smooth Muscle Cell Transdifferentiation and Pathological Vesel Remodeling
The Implication of Adenylyl Cyclase Isoform 8 and Its Regulation by the Notch Pathway in Vascular Smooth Muscle Cell Transdifferentiation and Pathological Vesel Remodeling - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook The Implication of Adenylyl Cyclase Isoform 8 and Its Regulation by the Notch Pathway in Vascular Smooth Muscle Cell Transdifferentiation and Pathological Vesel Remodeling write by Zela Talar Keuylian. This book was released on 2013. The Implication of Adenylyl Cyclase Isoform 8 and Its Regulation by the Notch Pathway in Vascular Smooth Muscle Cell Transdifferentiation and Pathological Vesel Remodeling available in PDF, EPUB and Kindle. Atherosclerosis is characterized by the narrowing of the arterial lumen termed "stenosis", due to the expansion of arterial plaques. One of the major contributing factors to the formation of lesions and the neo-intima during post-angioplasty restenosis is the phenotypic change of medial vascular smooth muscle cells. This process switches them from a quiescent/contractile phenotype to a secretory, proliferative, migratory one. My work consisted of elucidating some of the molecular mechanisms implicated in this switch. We showed that the expression of an adenylyl cyclase (AC) isoform, AC8, is implicated in both the inflammatory and migratory properties acquired by trans-differentiated VSMCs. In human atherosclerotic arteries we showed that only intimal VSMCs strongly express AC8; very few AC8 positive VSMCs were detected in the medial layer, either in atherosclerotic or healthy arteries. In the rat balloon injury model of restenosis, we showed a transitory increase of AC8 expression. In vitro, we demonstrated that AC8 expression is regulated by the Notch pathway; inhibiting Notch amplified AC8 expression and decreased Notch target genes Hrt1 and Hrt3. In the same model of restenosis, the transitory up-regulation of AC8 expression coincided with Notch3 down-regulation. These set of experiments demonstrated that the Notch pathway decreases IL1[beta]-mediated AC8 up-regulation in trans-differentiated VSMCs and suggests that AC8 expression, besides being induced by the proinflammatory cytokine IL1[beta],also depends on the down-regulation of the Notch pathway occurring in an inflammatory context. As a whole, my studies attribute a new role for AC8 in pathological vascular remodeling.
