scholarly journals Engagement of the CXCL12–CXCR4 Axis in the Interaction of Endothelial Progenitor Cell and Smooth Muscle Cell to Promote Phenotype Control and Guard Vascular Homeostasis

2022 ◽  
Vol 23 (2) ◽  
pp. 867
Author(s):  
Sebastian F. Mause ◽  
Elisabeth Ritzel ◽  
Annika Deck ◽  
Felix Vogt ◽  
Elisa A. Liehn
Keyword(s):  
Smooth Muscle ◽  
Feedback Loop ◽  
Cell Contact ◽  
Endothelial Progenitor ◽  
Vascular Homeostasis ◽  
Relevant Role ◽  
Direct Cell ◽  
And Migration ◽  
Cxcr4 Axis

Endothelial progenitor cells (EPCs) are involved in vascular repair and modulate properties of smooth muscle cells (SMCs) relevant for their contribution to neointima formation following injury. Considering the relevant role of the CXCL12–CXCR4 axis in vascular homeostasis and the potential of EPCs and SMCs to release CXCL12 and express CXCR4, we analyzed the engagement of the CXCL12–CXCR4 axis in various modes of EPC–SMC interaction relevant for injury- and lipid-induced atherosclerosis. We now demonstrate that the expression and release of CXCL12 is synergistically increased in a CXCR4-dependent mechanism following EPC–SMC interaction during co-cultivation or in response to recombinant CXCL12, thus establishing an amplifying feedback loop Additionally, mechanical injury of SMCs induces increased release of CXCL12, resulting in enhanced CXCR4-dependent recruitment of EPCs to SMCs. The CXCL12–CXCR4 axis is crucially engaged in the EPC-triggered augmentation of SMC migration and the attenuation of SMC apoptosis but not in the EPC-mediated increase in SMC proliferation. Compared to EPCs alone, the alliance of EPC–SMC is superior in promoting the CXCR4-dependent proliferation and migration of endothelial cells. When direct cell–cell contact is established, EPCs protect the contractile phenotype of SMCs via CXCL12–CXCR4 and reverse cholesterol-induced transdifferentiation toward a synthetic, macrophage-like phenotype. In conclusion we show that the interaction of EPCs and SMCs unleashes a CXCL12–CXCR4-based autoregulatory feedback loop promoting regenerative processes and mediating SMC phenotype control to potentially guard vascular homeostasis.

scholarly journals PDGFBB promotes proliferation and migration via regulating miR-1181/STAT3 axis in human pulmonary arterial smooth muscle cells

2018 ◽  
Vol 315 (6) ◽  
pp. L965-L976 ◽  
Author(s):  
Zhengjiang Qian ◽  
Yanjiao Li ◽  
Haiyang Yang ◽  
Jidong Chen ◽  
Xiang Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Causative Factor ◽  
Loss Of Function ◽  
Migration Flow ◽  
Pulmonary Arterial ◽  
And Migration ◽  
Proliferation And Migration

Platelet-derived growth factor (PDGF) can induce hyperproliferation of pulmonary artery smooth muscle cells (PASMCs), which is a key causative factor to the occurrence and progression of pulmonary arterial hypertension (PAH). We previously identified that miR-1181 is significantly downregulated by PDGFBB in human PASMCs. In this work, we further explore the function of miR-1181 and underlying regulatory mechanisms in PDGF-induced PASMCs. First, the expression pattern of miR-1181 was characterized under PDGFBB treatment, and PDGF receptor/PKCβ signaling was found to repress miR-1181 expression. Then, gain- and loss-of-function experiments were respectively conducted and revealed the prominent role of miR-1181 in inhibiting PASMC proliferation and migration. Flow cytometry analysis suggested that miR-1181 regulated the PASMC proliferation through influencing the cell cycle transition from G0/G1 to S phase. Moreover, we exhibited that miR-1181 targeting STAT3 formed a regulatory axis to modulate PASMC proliferation. Finally, serum miR-1181 expression was also observed to be reduced in adult and newborn patients with PAH. Overall, this study provides novel findings that the miR-1181/STAT3 axis mediated PDGFBB-induced dysfunction in human PASMCs, implying a potential use of miR-1181 as a therapeutic and diagnostic candidate for the vascular remodeling diseases.

Upregulation of intermediate-conductance Ca2+-activated K+channel (IKCa1) mediates phenotypic modulation of coronary smooth muscle

2006 ◽  
Vol 291 (5) ◽  
pp. H2493-H2503 ◽  
Author(s):  
D. L. Tharp ◽  
B. R. Wamhoff ◽  
J. R. Turk ◽  
D. K. Bowles
Keyword(s):  
Smooth Muscle ◽  
K Channel ◽  
Marker Genes ◽  
Phenotypic Modulation ◽  
Coronary Smooth Muscle ◽  
Differentiation Marker ◽  
And Migration ◽  
Muscle Myosin ◽  
Early Atherosclerosis

A hallmark of smooth muscle cell (SMC) phenotypic modulation in atherosclerosis and restenosis is suppression of SMC differentiation marker genes, proliferation, and migration. Blockade of intermediate-conductance Ca2+-activated K+channels (IKCa1) has been shown to inhibit restenosis after carotid balloon injury in the rat; however, whether IKCa1 plays a role in SMC phenotypic modulation is unknown. Our objective was to determine the role of IKCa1 channels in regulating coronary SMC phenotypic modulation and migration. In cultured porcine coronary SMCs, platelet-derived growth factor-BB (PDGF-BB) increased TRAM-34 (a specific IKCa1 inhibitor)-sensitive K+current 20-fold; increased IKCa1 promoter histone acetylation and c- jun binding; increased IKCa1 mRNA ∼4-fold; and potently decreased expression of the smooth muscle differentiation marker genes smooth muscle myosin heavy chain (SMMHC), smooth muscle α-actin (SMαA), and smoothelin-B, as well as myocardin. Importantly, TRAM-34 completely blocked PDGF-BB-induced suppression of SMMHC, SMαA, smoothelin-B, and myocardin and inhibited PDGF-BB-stimulated migration by ∼50%. Similar to TRAM-34, knockdown of endogenous IKCa1 with siRNA also prevented the PDGF-BB-induced increase in IKCa1 and decrease in SMMHC mRNA. In coronary arteries from high fat/high cholesterol-fed swine demonstrating signs of early atherosclerosis, IKCa1 expression was 22-fold higher and SMMHC, smoothelin-B, and myocardin expression significantly reduced in proliferating vs. nonproliferating medial cells. Our findings demonstrate that functional upregulation of IKCa1 is required for PDGF-BB-induced coronary SMC phenotypic modulation and migration and support a similar role for IKCa1 in coronary SMC during early coronary atherosclerosis.

Cyclic mechanical strain‐induced proliferation and migration of human airway smooth muscle cells: role of EMMPRIN and MMPs

2005 ◽  
Vol 19 (11) ◽  
pp. 1507-1509 ◽  
Author(s):  
Nadia A. Hasaneen ◽  
Stanley Zucker ◽  
Jian Cao ◽  
Christian Chiarelli ◽  
Reynold A. Panettieri ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Mechanical Strain ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Human Airway Smooth Muscle ◽  
And Migration ◽  
Proliferation And Migration

Role of GADD153 (growth arrest- and DNA damage-inducible gene 153) in vascular smooth muscle cell apoptosis

2001 ◽  
Vol 100 (3) ◽  
pp. 275-281 ◽  
Author(s):  
Michiya IGASE ◽  
Takafumi OKURA ◽  
Michitsugu NAKAMURA ◽  
Yasunori TAKATA ◽  
Yutaka KITAMI ◽  
...  
Keyword(s):  
Dna Damage ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Molecular Mechanisms ◽  
Growth Arrest ◽  
Cell Contact ◽  
Inducible Gene

GADD153 (growth arrest- and DNA damage-inducible gene 153) is expressed at very low levels in growing cells, but is markedly induced in response to a variety of cellular stresses, including glucose deprivation, exposure to genotoxic agents and other growth-arresting situations. Forced expression of GADD153 induces cell cycle arrest in many types of cells. It is also reported that GADD153 is directly associated with apoptosis. Recently we have reported that platelet-derived growth factor (PDGF)-BB induces apoptosis in cultured vascular smooth muscle cells (VSMC), but only when 100% confluency is reached. These results suggested that cell–cell contact inhibition (cell growth arrest) may be a critical factor for induction of VSMC apoptosis by PDGF-BB. In the present study, we explored the role of GADD153, one of a number of growth-arrest-related gene products, in the molecular mechanisms of VSMC apoptosis in vitro and in vivo. GADD153 was markedly induced at both the mRNA and protein levels, in parallel with the induction of VSMC apoptosis, after treatment with PDGF-BB. Moreover, overexpression of GADD153 in VSMC significantly reduced cell viability and induced apoptosis. In the carotid artery balloon injury model in rats, GADD153 protein was expressed in apoptotic VSMC which were positively stained by in situ DNA labelling. These results demonstrate an important role for GADD153 in the molecular mechanisms of VSMC apoptosis.

scholarly journals SIRT7 Regulates the Vascular Smooth Muscle Cells Proliferation and Migration via Wnt/β-Catenin Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Jianghua Zheng ◽  
Kai Chen ◽  
Haifei Wang ◽  
Zhilong Chen ◽  
Yong Xi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Counting ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

A huge amount of evidence indicates that sirtuin 7 (SIRT7), a key mediator of many cellular activities, plays a crucial role in the pathogenesis of various diseases. However, little is known about the role of SIRT7 in atherosclerosis. This study investigated the potential role of SIRT7 in regulating the proliferation and migration of human vascular smooth muscle cells (HAVSMCs) and its possible molecular mechanism. In this study, human vascular smooth muscle cells (HAVSMCs) were induced by oxidized low-density lipoprotein (ox-LDL) to establish atherosclerosis (AS) cell model. Immunofluorescence staining and Western blot were used to detect the level of α-SMA expression, which was a marker protein in AS. In addition, RT-qPCR and Western blot assay were applied for exploring the mRNA and protein expression levels of SIRT7, Wnt, β-catenin, and cyclin D1 after knockdown or overexpression of SIRT7. And, furthermore, Cell Counting Kit-8 assay, flow cytometry, and wound-healing assay were used to assess HAVSMCs proliferation, cell cycle, and migration. Dickkopf-1 (DKK-1), a secretory glycoprotein that can block Wnt/β-catenin pathway, was used in SIRT7 overexpression HAVSMCs; subsequently cells proliferation and migration were assessed by Cell Counting Kit-8 assay, flow cytometry analysis, and wound-healing assay. We found that knockdown of SIRT7 significantly promoted cell proliferation and migration, decreased the percentages of cells in the G1 and G2 phases, and increased those in the S phase and downregulated the protein expression levels of Wnt, β-catenin, and cyclin D1, while overexpression of SIRT7 had reverse results. After treatment with Wnt/beta-catenin pathway inhibitor DKK-1 in SIRT7 overexpression HAVSMCs, cell proliferation and migration were increased, respectively. In conclusion, SIRT7 inhibited HAVSMCs proliferation and migration via enhancing Wnt/β-catenin activation, which provided a novel therapeutic strategy for antiatherosclerosis.

Abstract 517: The CYP4A-20-HETE System Regulation of Endothelial Progenitor Cell Functions that Associated with Angiogenesis

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Li Chen ◽  
Alexander Braverman ◽  
Frank Zhang ◽  
John Falck ◽  
Ali Syed Arbab ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Vascular Effects ◽  
Endothelial Progenitor ◽  
Cell Functions ◽  
And Migration ◽  
Synthase Inhibitor ◽  
Proliferation And Migration

The CYP4A-20-HETE system regulates the neovascularization process via its potent vascular effects mainly on endothelial cells and vascular smooth muscle cells. Endothelial progenitor cells (EPC) also actively participate in physiological and pathological neovascularization. Our group first reported that the CYP4A-20-HETE system is present and functional in EPC derived from human umbilical cord blood (HUCB) and that EPC also respond to exogenous 20-HETE with increased proliferation and migration. We hypothesized that the angiogenic actions of the CYP4A-20-HETE system may involve regulation of EPC functions that associated with angiogenesis. In this study, we identified CYP4A11/22 as the main 20-HETE synthases in EPC derived from HUCB by real time PCR. We also examined the effects of exogenous 20-HETE on EPC adhesion since adhesion of EPC to extracellular matrix is an important aspect of EPC homing to the sites where angiogenesis is occurring. We found that 20-HETE (1 μM) increased EPC adhesion to fibronectin and SDF-1α coating by ∼40% and ∼35%, respectively. These increases in adhesion are completely abolished in the presence of 20-hydroxy-6, 15-eicosadienoic acid (20-HEDE), a 20-HETE antagonist. We further established the mouse ischemic hindlimb model to study the effects of pharmacological inhibition of the CYP4A/F-20-HETE system using the 20-HETE synthase inhibitor Dibromo-dodecenyl-methylsulfimide (DDMS) and 20-HEDE on compensatory angiogenesis in response to ischemia. Systemic treatment of animals with 10 mg/kg/day of either DDMS or 20-HEDE inhibited hindlimb compensatory angiogenesis by more than 50% without significant effects on the blood pressure. Specific targeting of the EPC-derived CYP4A-20-HETE system needs to be performed to further dissecting the role of systemic and EPC-derived 20-HETE on angiogenic processes. These findings implicates the CYP4A-20-HETE system as a novel regulator of EPC functions that are associated with angiogenesis and suggests that it can act as both an autocrine and paracrine regulatory factor.

Sign in / Sign up

Export Citation Format

Share Document