The interactions between serum response factor (SRF) and CArG elements are critical for smooth muscle cell (SMC) marker gene transcription. However, the mechanisms whereby SRF, which is expressed ubiquitously, contributes to SMC-specific transcription unknown. Myocardin was recently cloned as a coactivator of SRF in heart, but its role regulating CArG-dependent expression SMC differentiation genes has not been clearly elucidated. In this study, we examined function myocardin SMCs. adult...

Phenotypic switching of smooth muscle cells (SMCs) plays a key role in vascular proliferative diseases. We previously showed that Krüppel-like factor 4 (Klf4) suppressed SMC differentiation markers cultured SMCs. Here, we derive mice deficient for Klf4 by conditional gene ablation and analyze their phenotype following carotid injury. expression was rapidly induced SMCs control after injury but not Klf4-deficient mice. Injury-induced repression transiently delayed mutant exhibited enhanced...

Atherosclerosis is a vascular disease characterized by lipid deposition and inflammation within the arterial wall. Oxidized phospholipids (oxPLs), such as 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (oxPAPC) its constituents 1-palmytoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) are concentrated atherosclerotic lesions known to be potent proinflammatory mediators. Phenotypic switching of smooth muscle cells...

Background. Calciphylaxis, also called calcific uremic arteriolopathy, is a rare and often fatal complication of end-stage renal disease characterized by painful skin ulceration, necrosis, medial calcification intimal proliferation small arteries. Studies in western countries have reported incidences ranging from 1 to 4% chronic hemodialysis patients. Since no systematic studies calciphylaxis ever been performed Japan, we conducted nationwide survey case–control study identify the...

Phenotypic switching of vascular smooth muscle cells (SMCs), such as increased proliferation, enhanced migration, and downregulation SMC differentiation marker genes, is known to play a key role in the development atherosclerosis. However, factors mechanisms controlling this process are not fully understood. We recently showed that oxidized phospholipids, including 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC), which accumulate atherosclerotic lesions, potent repressors...

Phenotypic switching of vascular smooth muscle cells (VSMCs) is known to play a critical role in the development atherosclerosis. However, factors present within lesions that mediate VSMC phenotypic are unclear. Oxidized phospholipids (OxPLs), including 1-palmitoyl-2-(5-oxovaleroyl)- sn -glycero-3-phosphorylcholine (POVPC), active components minimally modified low density lipoprotein and have been previously shown induce multiple proatherogenic events endothelial macrophages, but their...

A hallmark of smooth muscle cell (SMC) phenotypic switching is suppression SMC marker gene expression. Although myocardin has been shown to be a key regulator this process, the role its related factors, MKL1 and MKL2, in remains unknown. The present studies were aimed at determining if: 1) MKL factors contribute expression genes cultured SMCs; 2) platelet-derived growth factor-BB (PDGF-BB)-induced repression mediated by factors. Results gain- loss-of-function experiments showed that...

Background Vascular proliferative diseases such as atherosclerosis are inflammatory disorders involving multiple cell types including macrophages, lymphocytes, endothelial cells, and smooth muscle cells ( SMC s). Although activation of the nuclear factor‐κB NF ‐κB) pathway in vessels has been shown to be critical for progression vascular diseases, cell‐autonomous role ‐κB within s not fully understood. Methods Results We generated ‐selective truncated IκB expressing SM 22α‐Cre/IκBΔN) mice,...

Myocardin, a coactivator of serum response factor, has been shown to be required for expression multiple CArG-dependent smooth muscle cell (SMC) marker genes. The aim the present study was determine whether myocardin alone is sufficient induce SMC lineage in multipotential stem cells as evidenced by activation entire differentiation program.Overexpression induced only subset genes, including (SM) alpha-actin, SM-myosin heavy chain (MHC), SM22alpha, calponin, and desmin A404 precursor cells,...

CC(A/T)6GG–dependent (CArG-dependent) and serum response factor–dependent (SRF-dependent) mechanisms are required for gene expression in smooth muscle cells (SMCs). However, an unusual feature of many SMC-selective promoter CArG elements is that they contain a conserved single G or C substitution their central A/T-rich region, which reduces binding affinity ubiquitously expressed SRF. We hypothesized this degeneracy contributes to cell-specific α-actin vivo, since c-fos consensus CArGs the...

The incidence, characteristics of action, and pathogenetic importance blocking type anti-TSH receptor antibody were examined in patients with autoimmune thyroiditis. Serum immunoglobulin G (IgG) from 8 20 nongoitrous hypothyroidism contained substantial amounts TSH binding inhibitor (TBII) activity. Newborn infants a patient the greatest TBII activity had neonatal transient hypothyroidism. In sera goitrous euthryoid chronic thyroiditis, only weakly positive or negative was found. IgGs these...

There has been considerable controversy regarding the lineage relationship between smooth muscle cells (SMCs) and myofibroblasts, because they express a number of common cell-selective markers including (SM) alpha-actin. We have shown previously that MCAT elements within SM alpha-actin promoter confer differential activity in cultured SMCs versus myofibroblasts. In present study, to determine role vivo, we generated transgenic mice harboring an promoter-enhancer-LacZ reporter gene containing...

Kruppel-like factor 4 (KLF4) plays an important role in vascular diseases, including atherosclerosis and injury. Although KLF4 is expressed the heart addition to cells, of cardiac disease has not been fully determined. The goals this study were investigate hypertrophy determine underlying mechanisms. Cardiomyocyte-specific Klf4 knockout (CM KO) mice generated by Cre/LoxP technique. Cardiac was induced chronic infusion β-adrenoreceptor agonist isoproterenol (ISO). Results showed that...

Background Krüppel‐like factor 4 (Klf4) is involved in a variety of cellular functions by activating or repressing the transcription multiple genes. Results previous studies showed that tamoxifen‐inducible global deletion Klf4 gene mice accelerated neointimal formation following vascular injury, part via enhanced proliferation smooth muscle cells ( SMC s). Because also expressed non‐ s including endothelial EC s), we determined if Tie2 promoter‐dependent and hematopoietic affected...

Superoxide has been implicated in the pathogenesis of ischemic stroke and atherosclerosis. NADPH oxidase, a major source superoxide generation neutrophils vascular system, plays critical role injury atherogenesis. Recently, an association between C242T polymorphism p22 PHOX, essential component coronary artery disease (CAD) reported several studies. To investigate relationship PHOX cerebrovascular (CVD), we conducted case-control study.We recruited 226 CVD patients (atherothrombotic...

Endothelial cells participate in the pathophysiology of ischemic AKI by increasing expression cell adhesion molecules and recruiting inflammatory cells. We previously showed that endothelial Krüppel-like factor 4 (Klf4) regulates vascular molecule 1 (Vcam1) neointimal formation after carotid injury. In this study, we determined whether Klf4 is involved using conditional knockout (Klf4 cKO) mice generated breeding Tek-Cre floxed mice. cKO were phenotypically normal before surgery. However,...