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vascular smooth muscle cell clonality

Abdul Q Sheikh, Fatima Zahra Saddouk, Aglaia Ntokou, Renata Mazurek, Daniel M Greif
Pulmonary hypertension is a devastating disease characterized by excessive vascular muscularization. We previously demonstrated primed platelet-derived growth factor receptor β+ (PDGFR-β+ )/smooth muscle cell (SMC) marker+ progenitors at the muscular-unmuscular arteriole border in the normal lung, and in hypoxia-induced pulmonary hypertension, a single primed cell migrates distally and expands clonally, giving rise to most of the pathological smooth muscle coating of small arterioles. Little is known regarding the molecular mechanisms underlying this process...
April 24, 2018: Cell Reports
Moritz Lehners, Hyazinth Dobrowinski, Susanne Feil, Robert Feil
Cyclic GMP regulates multiple cell types and functions of the cardiovascular system. This review summarizes the effects of cGMP on the growth and survival of vascular smooth muscle cells (VSMCs), which display remarkable phenotypic plasticity during the development of vascular diseases, such as atherosclerosis. Recent studies have shown that VSMCs contribute to the development of atherosclerotic plaques by clonal expansion and transdifferentiation to macrophage-like cells. VSMCs express a variety of cGMP generators and effectors, including NO-sensitive guanylyl cyclase (NO-GC) and cGMP-dependent protein kinase type I (cGKI), respectively...
April 19, 2018: Journal of Cardiovascular Development and Disease
Akhilesh Kumar, Saritha Sandra D'Souza, Oleg V Moskvin, Huishi Toh, Bowen Wang, Jue Zhang, Scott Swanson, Lian-Wang Guo, James A Thomson, Igor I Slukvin
Elucidating the pathways that lead to vasculogenic cells, and being able to identify their progenitors and lineage-restricted cells, is critical to the establishment of human pluripotent stem cell (hPSC) models for vascular diseases and development of vascular therapies. Here, we find that mesoderm-derived pericytes (PCs) and smooth muscle cells (SMCs) originate from a clonal mesenchymal progenitor mesenchymoangioblast (MB). In clonogenic cultures, MBs differentiate into primitive PDGFRβ+ CD271+ CD73- mesenchymal progenitors, which give rise to proliferative PCs, SMCs, and mesenchymal stem/stromal cells...
May 30, 2017: Cell Reports
Gianandrea Pasquinelli, William G Thilly, Elena V Gostjeva, Paola Todeschini, Giuseppe Cianciolo, Claudio Ronco, Gaetano La Manna
Chronic kidney disease (CKD) exacerbating vascular disease poses a major challenge to nephrology. Surgically placed vascular fistulas, as an aid to hemodialysis prior to kidney transplant, have extended many lives, while post-surgical restenosis closure of the fistula by smooth muscle cells affects many lives. When post-surgical restenosis is developed, palliative measures are almost always surgical: there are no effective drug treatments. In this study, we offer a testable hypothesis that effects of CKD on widely distributed vascular diseases and the phenomenon of fistula restenosis are both driven by the pathologic creation of non-dividing smooth muscle cells via asymmetric division of exponentially increasing metakaryotic stem cells...
2017: Contributions to Nephrology
Keegan J Bohn, Baolin Li, Xiaofang Huang, Bianca N Mason, Anne-Sophie Wattiez, Adisa Kuburas, Christopher S Walker, Peiyi Yang, Jianliang Yu, Beverly A Heinz, Kirk W Johnson, Andrew F Russo
BACKGROUND AND PURPOSE: CGRP is a potent vasodilator and nociceptive neuropeptide linked to migraine. CGRP receptors are heterodimers of receptor activity modifying protein 1 (RAMP1) and either calcitonin receptor-like receptor (CLR; forms canonical CGRP receptor) or calcitonin receptor (CT receptor; forms AMY1 receptor). The goal of this study was to test whether transgenic mice globally expressing human RAMP1 have increased CGRP receptor activity and whether the receptors are sensitive to human selective antagonist telcagepant...
June 2017: British Journal of Pharmacology
Boon-Seng Soh, Shi-Yan Ng, Hao Wu, Kristina Buac, Joo-Hye C Park, Xiaojun Lian, Jiejia Xu, Kylie S Foo, Ulrika Felldin, Xiaobing He, Massimo Nichane, Henry Yang, Lei Bu, Ronald A Li, Bing Lim, Kenneth R Chien
Coronary arteriogenesis is a central step in cardiogenesis, requiring coordinated generation and integration of endothelial cell and vascular smooth muscle cells. At present, it is unclear whether the cell fate programme of cardiac progenitors to generate complex muscular or vascular structures is entirely cell autonomous. Here we demonstrate the intrinsic ability of vascular progenitors to develop and self-organize into cardiac tissues by clonally isolating and expanding second heart field cardiovascular progenitors using WNT3A and endothelin-1 (EDN1) human recombinant proteins...
March 8, 2016: Nature Communications
Abdul Q Sheikh, Ashish Misra, Ivan O Rosas, Ralf H Adams, Daniel M Greif
Excess and ectopic smooth muscle cells (SMCs) are central to cardiovascular disease pathogenesis, but underlying mechanisms are poorly defined. For instance, pulmonary hypertension (PH) or elevated pulmonary artery blood pressure is a devastating disease with distal extension of smooth muscle to normally unmuscularized pulmonary arterioles. We identify novel SMC progenitors that are located at the pulmonary arteriole muscular-unmuscular border and express both SMC markers and the undifferentiated mesenchyme marker platelet-derived growth factor receptor-β (PDGFR-β)...
October 7, 2015: Science Translational Medicine
Gabriella Lania, Rosa Ferrentino, Antonio Baldini
The T-box transcription factor TBX1 has critical roles in maintaining proliferation and inhibiting differentiation of cardiac progenitor cells of the second heart field (SHF). Haploinsufficiency of the gene that encodes it is a cause of congenital heart disease. Here, we developed an embryonic stem (ES) cell-based model in which Tbx1 expression can be modulated by tetracycline. Using this model, we found that TBX1 down regulates the expression of VEGFR2, and we confirmed this finding in vivo during embryonic development...
2015: PloS One
M B Gravanis, R Waksman
Although the precise pathogenesis of restenosis after percutaneous transluminal coronary angioplasty (PTCA) remains somewhat elusive, our understanding about the reparative phenomena at the site of dilatation has been significantly improved in recent years. Thus, restenosis appears to be the result of migration, proliferation, and excessive matrix formation by smooth muscle cells plus vascular wall remodeling leading to chronic recoil (constriction). Proposed pharmacotherapies to prevent restenosis have been ineffective in humans, in spite of a relative success in certain experimental animals...
January 1997: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
Xiaojun Lian, Xiaoping Bao, Abraham Al-Ahmad, Jialu Liu, Yue Wu, Wentao Dong, Kaitlin K Dunn, Eric V Shusta, Sean P Palecek
Human pluripotent stem cell (hPSC)-derived endothelial cells and their progenitors may provide the means for vascularization of tissue-engineered constructs and can serve as models to study vascular development and disease. Here, we report a method to efficiently produce endothelial cells from hPSCs via GSK3 inhibition and culture in defined media to direct hPSC differentiation to CD34(+)CD31(+) endothelial progenitors. Exogenous vascular endothelial growth factor (VEGF) treatment was dispensable, and endothelial progenitor differentiation was β-catenin dependent...
November 11, 2014: Stem Cell Reports
Susanne Feil, Birgit Fehrenbacher, Robert Lukowski, Frank Essmann, Klaus Schulze-Osthoff, Martin Schaller, Robert Feil
RATIONALE: Atherosclerosis is a widespread and devastating disease, but the origins of cells within atherosclerotic plaques are not well defined. OBJECTIVE: To investigate the specific contribution of vascular smooth muscle cells (SMCs) to atherosclerotic plaque formation by genetic inducible fate mapping in mice. METHODS AND RESULTS: Vascular SMCs were genetically pulse-labeled using the tamoxifen-dependent Cre recombinase, CreER(T2), expressed from the endogenous SM22α locus combined with Cre-activatable reporter genes that were integrated into the ROSA26 locus...
September 12, 2014: Circulation Research
Sarah J Holdsworth-Carson, Marina Zaitseva, Jane E Girling, Beverley J Vollenhoven, Peter A W Rogers
Uterine fibroids are a prevalent gynaecological condition in reproductive-aged women and are the commonest reason for hysterectomy. The cellular composition of clonal fibroids are heterogeneous, with phenotypically dissimilar cells that include smooth muscle cells (SMC), vascular SMC (VSMC) and fibroblasts. The aim of our study was to investigate genes that are commonly differentially expressed between fibroid and myometrial whole tissues in phenotypically different sub-populations of cells isolated from fibroid and myometrium...
May 2014: Reproduction: the Official Journal of the Society for the Study of Fertility
Sarah J Holdsworth-Carson, Marina Zaitseva, Beverley J Vollenhoven, Peter A W Rogers
Uterine fibroids are conventionally defined as clonally derived benign tumours from the proliferation of a single smooth muscle cell (SMC). We have previously identified fibroblast-like cells in fibroids, the presence of which raises the question as to whether all cells within the fibroid have the same clonal origin. The first aim of this study was to develop a fluorescence-activated cell sorting (FACS)-based method to isolate different cell types from human myometrium and fibroid tissues. Secondly, we aimed to use X chromosome inactivation analysis to determine the clonality of cell subpopulations isolated from myometrial and fibroid tissues...
March 2014: Molecular Human Reproduction
Nicolas Espagnolle, Fabien Guilloton, Frédéric Deschaseaux, Mélanie Gadelorge, Luc Sensébé, Philippe Bourin
Bone marrow mesenchymal stem cells (MSCs) are plastic adherent cells that can differentiate into various tissue lineages, including osteoblasts, adipocytes and chondrocytes. However, this progenitor property is not shared by all cells within the MSC population. In addition, MSCs vary in their proliferation capacity and expression of markers. Because of heterogeneity of CD146 expression in the MSC population, we compared CD146(-/Low) and CD146(High) cells under clonal conditions and after sorting of the non-clonal cell population to determine whether this expression is associated with specific functions...
January 2014: Journal of Cellular and Molecular Medicine
Kathy O Lui, Lior Zangi, Eduardo A Silva, Lei Bu, Makoto Sahara, Ronald A Li, David J Mooney, Kenneth R Chien
Distinct families of multipotent heart progenitors play a central role in the generation of diverse cardiac, smooth muscle and endothelial cell lineages during mammalian cardiogenesis. The identification of precise paracrine signals that drive the cell-fate decision of these multipotent progenitors, and the development of novel approaches to deliver these signals in vivo, are critical steps towards unlocking their regenerative therapeutic potential. Herein, we have identified a family of human cardiac endothelial intermediates located in outflow tract of the early human fetal hearts (OFT-ECs), characterized by coexpression of Isl1 and CD144/vWF...
October 2013: Cell Research
Saurabh Aggarwal, Christine M Gross, Shruti Sharma, Jeffrey R Fineman, Stephen M Black
The pathogenesis of pulmonary hypertension is a complex multifactorial process that involves the remodeling of pulmonary arteries. This remodeling process encompasses concentric medial thickening of small arterioles, neomuscularization of previously nonmuscular capillary-like vessels, and structural wall changes in larger pulmonary arteries. The pulmonary arterial muscularization is characterized by vascular smooth muscle cell hyperplasia and hypertrophy. In addition, in uncontrolled pulmonary hypertension, the clonal expansion of apoptosis-resistant endothelial cells leads to the formation of plexiform lesions...
July 2013: Comprehensive Physiology
Tien Peng, Ying Tian, Cornelis J Boogerd, Min Min Lu, Rachel S Kadzik, Kathleen M Stewart, Sylvia M Evans, Edward E Morrisey
Co-development of the cardiovascular and pulmonary systems is a recent evolutionary adaption to terrestrial life that couples cardiac output with the gas exchange function of the lung. Here we show that the murine pulmonary vasculature develops even in the absence of lung development. We have identified a population of multipotent cardiopulmonary mesoderm progenitors (CPPs) within the posterior pole of the heart that are marked by the expression of Wnt2, Gli1 and Isl1. We show that CPPs arise from cardiac progenitors before lung development...
August 29, 2013: Nature
C Bai, L Hou, M Zhang, L Wang, W Guan, Y Ma
OBJECTIVES: Many kinds of cardiac progenitor cell populations have been identified, including c-kit(+) , Nkx2.5(+) s and GATA4(+) cells. However, these progenitors have limited ability to differentiate into different cardiac cell types. Recently, a new kind of cardiac progenitor cell named the multipotent Isl1(+) cardiovascular progenitor (MICPs) has been identified, which also expresses Nkx2.5, GATA4, CD34 and Flk1. MATERIALS AND METHODS: In this study, we have isolated and characterized MICPs from chicken embryonic heart tissues using immunofluorescence and PCR...
April 2013: Cell Proliferation
Sun-Hwa Song, Woojin Jung, Koung Li Kim, Wonpyo Hong, Hyun Ok Kim, Kyung-Ah Lee, Ki-Young Lee, Wonhee Suh
Identification of differentially expressed genes in angioblasts derived from human embryonic stem cells (hESCs) is of great interest for elucidating the molecular mechanisms underlying human vasculogenesis. The aim of this study was to define hESC-derived angioblasts at the clonal level and to perform comparative transcriptional analysis to characterize their distinct gene expression profiles. In a clonal analysis performed in cell-specific differentiation media, hESC-derived CD34(+)CD31(+) cells were identified as angioblasts in that they exhibited a significantly higher ability to form endothelial cell (EC) and smooth muscle cell (SMC) colonies than CD34(+)CD31(-) and CD34(-) cell populations did...
May 1, 2013: Experimental Cell Research
Reza Ardehali, Shah R Ali, Matthew A Inlay, Oscar J Abilez, Michael Q Chen, Timothy A Blauwkamp, Masayuki Yazawa, Yongquan Gong, Roeland Nusse, Micha Drukker, Irving L Weissman
A goal of regenerative medicine is to identify cardiovascular progenitors from human ES cells (hESCs) that can functionally integrate into the human heart. Previous studies to evaluate the developmental potential of candidate hESC-derived progenitors have delivered these cells into murine and porcine cardiac tissue, with inconclusive evidence regarding the capacity of these human cells to physiologically engraft in xenotransplantation assays. Further, the potential of hESC-derived cardiovascular lineage cells to functionally couple to human myocardium remains untested and unknown...
February 26, 2013: Proceedings of the National Academy of Sciences of the United States of America
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