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vascular smooth muscle cell lineage tracing

Andrew L Durham, Mei Y Speer, Marta Scatena, Cecilia M Giachelli, Catherine M Shanahan
Vascular calcification is associated with a significant increase in all-cause mortality and atherosclerotic plaque rupture. Calcification has been determined to be an active process driven in part by vascular smooth muscle cell (VSMC) transdifferentiation within the vascular wall. Historically, VSMC phenotype switching has been viewed as binary, with the cells able to adopt a physiological contractile phenotype or an alternate 'synthetic' phenotype in response to injury. More recent work, including lineage tracing has however revealed that VSMCs are able to adopt a number of phenotypes, including calcific (osteogenic, chondrocytic, and osteoclastic), adipogenic, and macrophagic phenotypes...
March 15, 2018: Cardiovascular Research
Nicholas J Leeper, Lars Maegdefessel
The vascular smooth muscle cell (SMC) is one of the most plastic cells in the body. Understanding how non-coding RNAs regulate SMC cell-fate decision making in the vasculature has significantly enhanced our understanding of disease development, and opened up exciting new avenues for potential therapeutic applications. Recent studies on SMC physiology have in addition challenged our traditional view on their role and contribution to vascular disease, mainly in the setting of atherosclerosis as well as aneurysm disease, and restenosis after angioplasties...
December 29, 2017: Cardiovascular Research
Karina N Dubé, Tonia M Thomas, Sonali Munshaw, Mala Rohling, Paul R Riley, Nicola Smart
Restoring blood flow after myocardial infarction (MI) is essential for survival of existing and newly regenerated tissue. Endogenous vascular repair processes are deployed following injury but are poorly understood. We sought to determine whether developmental mechanisms of coronary vessel formation are intrinsically reactivated in the adult mouse after MI. Using pulse-chase genetic lineage tracing, we establish that de novo vessel formation constitutes a substantial component of the neovascular response, with apparent cellular contributions from the endocardium and coronary sinus...
November 16, 2017: JCI Insight
Urmas Roostalu, Bashar Aldeiri, Alessandra Albertini, Neil E Humphreys, Maj Simonsen-Jackson, Jason K Wong, Giulio Cossu
Rationale: Vascular smooth muscle turnover has important implications for blood vessel repair and for the development of cardiovascular diseases, yet lack of specific transgenic animal models has prevented it's in vivo analysis. Objective: To characterize the dynamics and mechanisms of vascular smooth muscle turnover from the earliest stages of embryonic development to arterial repair in the adult. Methods and Results: We show that CD146 is transiently expressed in vascular smooth muscle development. By using CRISPR-Cas9 genome editing and in vitro smooth muscle differentiation assay we demonstrate that CD146 regulates the balance between proliferation and differentiation...
November 22, 2017: Circulation Research
Meera Murgai, Wei Ju, Matthew Eason, Jessica Kline, Daniel W Beury, Sabina Kaczanowska, Markku M Miettinen, Michael Kruhlak, Haiyan Lei, Jack F Shern, Olga A Cherepanova, Gary K Owens, Rosandra N Kaplan
A deeper understanding of the metastatic process is required for the development of new therapies that improve patient survival. Metastatic tumor cell growth and survival in distant organs is facilitated by the formation of a pre-metastatic niche that is composed of hematopoietic cells, stromal cells and extracellular matrix (ECM). Perivascular cells, including vascular smooth muscle cells (vSMCs) and pericytes, are involved in new vessel formation and in promoting stem cell maintenance and proliferation. Given the well-described plasticity of perivascular cells, we hypothesized that perivascular cells similarly regulate tumor cell fate at metastatic sites...
October 2017: Nature Medicine
Kazuyuki Tsujino, John T Li, Tatsuya Tsukui, Xin Ren, Latifa Bakiri, Erwin Wagner, Dean Sheppard
Mice that globally overexpress the transcription factor Fos-related antigen-2 (Fra-2) develop extensive pulmonary fibrosis and pulmonary vascular remodeling. To determine if these phenotypes are a consequence of ectopic Fra-2 expression in vascular smooth muscle cells and myofibroblasts, we generated mice that overexpress Fra-2 specifically in these cell types (α-SMA-rtTA;tetO-Fra-2). Surprisingly, these mice did not develop vascular remodeling or pulmonary fibrosis but did develop a spontaneous emphysema-like phenotype characterized by alveolar enlargement...
November 1, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
Dong Wang, Fan Wu, Haoyong Yuan, Aijun Wang, Gyeong Jin Kang, Tan Truong, Lu Chen, Andrew S McCallion, Xiaohua Gong, Song Li
OBJECTIVE: Previous genetic lineage tracing studies showed that Sox10(+) cells differentiate into vascular mural cells, limited to neural crest-derived blood vessels in craniofacial tissues, aortic arch, pulmonary arch arteries, brachiocephalic, carotid arteries, and thymus. The purpose of this study was to investigate the contribution of Sox10(+) cells to the vascular development in other tissues and organs and their relationship with neural crest. APPROACH AND RESULTS: Using genetic lineage tracing technique based on Cre/LoxP system, we examined blood vessels in the adult organs of the mice expressing Sox10-Cre/Rosa-LoxP-red fluorescent protein or Wnt1-Cre/Rosa-LoxP-red fluorescent protein by immunohistological analysis...
September 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
Baoqi Yu, Qishan Chen, Alexandra Le Bras, Li Zhang, Qingbo Xu
SIGNIFICANCE: Atherosclerosis is a major cause for the death of human beings, and takes place in large and middle-sized arteries. The pathogenesis of the disease has been widely investigated and new findings on vascular stem/progenitor cells could have impact on vascular regeneration. Recent Advances: Recent studies have shown that abundant stem/progenitor cells present in the vessel wall are mainly responsible for cell accumulation in the intima during vascular remodeling. It has been demonstrated that the mobilization and recruitment of tissue-resident stem/progenitor cells give rise to endothelial and smooth muscle cells, which participate in vascular repair and remodeling such as neointimal hyperplasia and arteriosclerosis...
May 24, 2017: Antioxidants & Redox Signaling
Yao Wei Lu, Anthony M Lowery, Li-Yan Sun, Harold A Singer, Guohao Dai, Alejandro P Adam, Peter A Vincent, John J Schwarz
OBJECTIVE: Laminar flow activates myocyte enhancer factor 2 (MEF2) transcription factors in vitro to induce expression of atheroprotective genes in the endothelium. Here we sought to establish the role of Mef2c in the vascular endothelium in vivo. APPROACH AND RESULTS: To study endothelial Mef2c, we generated endothelial-specific deletion of Mef2c using Tie2-Cre or Cdh5-Cre-ER(T2) and examined aortas and carotid arteries by en face immunofluorescence. We observed enhanced actin stress fiber formation in the Mef2c-deleted thoracic aortic endothelium (laminar flow region), similar to those observed in normal aortic inner curvature (disturbed flow region)...
July 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
Christa F Gaskill, Erica J Carrier, Jonathan A Kropski, Nathaniel C Bloodworth, Swapna Menon, Robert F Foronjy, M Mark Taketo, Charles C Hong, Eric D Austin, James D West, Anna L Means, James E Loyd, W David Merryman, Anna R Hemnes, Stijn De Langhe, Timothy S Blackwell, Dwight J Klemm, Susan M Majka
Pulmonary vascular disease is characterized by remodeling and loss of microvessels and is typically attributed to pathological responses in vascular endothelium or abnormal smooth muscle cell phenotypes. We have challenged this understanding by defining an adult pulmonary mesenchymal progenitor cell (MPC) that regulates both microvascular function and angiogenesis. The current understanding of adult MPCs and their roles in homeostasis versus disease has been limited by a lack of genetic markers with which to lineage label multipotent mesenchyme and trace the differentiation of these MPCs into vascular lineages...
June 1, 2017: Journal of Clinical Investigation
Alena Moiseenko, Vahid Kheirollahi, Cho-Ming Chao, Negah Ahmadvand, Jennifer Quantius, Jochen Wilhelm, Susanne Herold, Katrin Ahlbrecht, Rory E Morty, Albert A Rizvanov, Parviz Minoo, Elie El Agha, Saverio Bellusci
ACTA2 expression identifies pulmonary airway and vascular smooth muscle cells (SMCs) as well as alveolar myofibroblasts (MYF). Mesenchymal progenitors expressing fibroblast growth factor 10 (Fgf10), Wilms tumor 1 (Wt1), or glioma-associated oncogene 1 (Gli1) contribute to SMC formation from early stages of lung development. However, their respective contribution and specificity to the SMC and/or alveolar MYF lineages remain controversial. In addition, the contribution of mesenchymal cells undergoing active WNT signaling remains unknown...
April 3, 2017: Stem Cells
Jinjing Zhao, Frances L Jourd'heuil, Min Xue, David Conti, Reynold I Lopez-Soler, Roman Ginnan, Arif Asif, Harold A Singer, David Jourd'heuil, Xiaochun Long
BACKGROUND: The arteriovenous fistula (AVF) is the preferred form of hemodialysis access for patients with chronic kidney disease. However, AVFs are associated with significant problems including high incidence of both early and late failures, usually attributed to inadequate venous arterialization and neointimal hyperplasia, respectively. Understanding the cellular basis of venous remodeling in the setting of AVF could provide targets for improving AVF patency rates. METHODS AND RESULTS: A novel vascular smooth muscle cell (VSMC) lineage tracing reporter mouse, Myh11-Cre/ERT2-mTmG, was used to track mature VSMCs in a clinically relevant AVF mouse model created by a jugular vein branch end to carotid artery side anastomosis...
March 30, 2017: Journal of the American Heart Association
Nuno Guimarães-Camboa, Paola Cattaneo, Yunfu Sun, Thomas Moore-Morris, Yusu Gu, Nancy D Dalton, Edward Rockenstein, Eliezer Masliah, Kirk L Peterson, William B Stallcup, Ju Chen, Sylvia M Evans
Pericytes are widely believed to function as mesenchymal stem cells (MSCs), multipotent tissue-resident progenitors with great potential for regenerative medicine. Cultured pericytes isolated from distinct tissues can differentiate into multiple cell types in vitro or following transplantation in vivo. However, the cell fate plasticity of endogenous pericytes in vivo remains unclear. Here, we show that the transcription factor Tbx18 selectively marks pericytes and vascular smooth muscle cells in multiple organs of adult mouse...
March 2, 2017: Cell Stem Cell
Falei Yuan, Dong Wang, Kang Xu, Jixian Wang, Zhijun Zhang, Li Yang, Guo-Yuan Yang, Song Li
The de-differentiation and proliferation of smooth muscle cells (SMCs) are widely accepted as the major contributor to vascular remodeling. However, recent studies indicate that vascular stem cells (VSCs) also play an important role, but their relative contribution remains to be elucidated. In this study, we used genetic lineage tracing approach to further investigate the contribution of SMCs and VSCs to neointimal thickening in response to endothelium denudation injury or artery ligation. In vitro and in vivo analysis of MYH11-cre/Rosa-loxP-RFP mouse artery showed that SMCs proliferated at a much slower rate than non-SMCs...
2017: PloS One
Joel Chappell, Jennifer L Harman, Vagheesh M Narasimhan, Haixiang Yu, Kirsty Foote, Benjamin D Simons, Martin R Bennett, Helle F Jørgensen
RATIONALE: Vascular smooth muscle cell (VSMC) accumulation is a hallmark of atherosclerosis and vascular injury. However, fundamental aspects of proliferation and the phenotypic changes within individual VSMCs, which underlie vascular disease, remain unresolved. In particular, it is not known whether all VSMCs proliferate and display plasticity or whether individual cells can switch to multiple phenotypes. OBJECTIVE: To assess whether proliferation and plasticity in disease is a general characteristic of VSMCs or a feature of a subset of cells...
December 9, 2016: Circulation Research
Sumaya Dauleh, Ilaria Santeramo, Claire Fielding, Kelly Ward, Anne Herrmann, Patricia Murray, Bettina Wilm
The human omentum has been long regarded as a healing patch, used by surgeons for its ability to immunomodulate, repair and vascularise injured tissues. A major component of the omentum are mesothelial cells, which display some of the characteristics of mesenchymal stem/stromal cells. For instance, lineage tracing studies have shown that mesothelial cells give rise to adipocytes and vascular smooth muscle cells, and human and rat mesothelial cells have been shown to differentiate into osteoblast- and adipocyte-like cells in vitro, indicating that they have considerable plasticity...
2016: PloS One
Julián Albarrán-Juárez, Harmandeep Kaur, Myriam Grimm, Stefan Offermanns, Nina Wettschureck
BACKGROUND AND AIMS: Despite the clinical importance of atherosclerosis, the origin of cells within atherosclerotic plaques is not fully understood. Due to the lack of a definitive lineage-tracing strategy, previous studies have provided controversial results about the origin of cells expressing smooth muscle and macrophage markers in atherosclerosis. We here aim to identify the origin of vascular smooth muscle (SM) cells and macrophages within atherosclerosis lesions. METHODS: We combined a genetic fate mapping approach with single cell expression analysis in a murine model of atherosclerosis...
August 2016: Atherosclerosis
Maria H Ulvmar, Ines Martinez-Corral, Lukas Stanczuk, Taija Mäkinen
The Pdgfrb-Cre line has been used as a tool to specifically target pericytes and vascular smooth muscle cells. Recent studies showed additional targeting of cardiac and mesenteric lymphatic endothelial cells (LECs) by the Pdgfrb-Cre transgene. In the heart, this was suggested to provide evidence for a previously unknown nonvenous source of LECs originating from yolk sac (YS) hemogenic endothelium (HemEC). Here we show that Pdgfrb-Cre does not, however, target YS HemEC or YS-derived erythro-myeloid progenitors (EMPs)...
2016: Genesis: the Journal of Genetics and Development
Koji Ando, Shigetomo Fukuhara, Nanae Izumi, Hiroyuki Nakajima, Hajime Fukui, Robert N Kelsh, Naoki Mochizuki
Mural cells (MCs) consisting of vascular smooth muscle cells and pericytes cover the endothelial cells (ECs) to regulate vascular stability and homeostasis. Here, we clarified the mechanism by which MCs develop and cover ECs by generating transgenic zebrafish lines that allow live imaging of MCs and by lineage tracing in vivo To cover cranial vessels, MCs derived from either neural crest cells or mesoderm emerged around the preformed EC tubes, proliferated and migrated along EC tubes. During their migration, the MCs moved forward by extending their processes along the inter-EC junctions, suggesting a role for inter-EC junctions as a scaffold for MC migration...
April 15, 2016: Development
Qiaozhen Liu, Hui Zhang, Xueying Tian, Lingjuan He, Xiuzhen Huang, Zhen Tan, Yan Yan, Sylvia M Evans, Joshua D Wythe, Bin Zhou
Recent identification of the neonatal 2nd coronary vascular population (2nd CVP) suggests that a subset of these vessels form de novo and mature in the inner myocardial wall of the postnatal heart. However, the origin of smooth muscle cells (SMCs) in the postnatal 2nd CVP remains undetermined. Using a tamoxifen-inducible Wt1-CreER driver and a Rosa26-RFP reporter line, we traced the lineage of epicardial cells to determine if they contribute to SMCs of the 2nd CVP. Late embryonic and postnatal induction of Wt1-CreER activity demonstrated that at these stages Wt1-labeled epicardium does not significantly migrate into the myocardium to form SMCs...
March 18, 2016: Biochemical and Biophysical Research Communications
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