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Showing papers on "Smoothelin published in 2005"


Journal ArticleDOI
TL;DR: It is suggested that Notch promotes changes in hVSMC phenotype via activation of CBF-1/RBP-Jkappa-dependent pathways in vitro and contributes to the phenotypic response of VSMCs to cyclic strain-induced changes in VSMC differentiation.
Abstract: Vascular smooth muscle cell (VSMC) phenotypic modulation is a key factor in vascular pathology. We have investigated the role of Notch receptor signaling in controlling human vascular smooth muscle...

112 citations


Journal ArticleDOI
TL;DR: Intimal SMCs of all situations exhibit a phenotypic profile, suggesting that they have modulated into myofibroblasts (MFs), and the high accumulation of α-SMA–positive MFs in erosions compared with stable plaques correlates with the higher appearance of thrombotic complications in this situation.
Abstract: Objectives— Characterize the phenotypic features of media and intima coronary artery smooth muscle cells (SMCs) in mildly stenotic plaques, erosions, stable plaques, and in-stent restenosis. Methods and Results— Expression of α-smooth muscle actin (α-SMA), smooth muscle myosin heavy chains (SMMHCs), and smoothelin was investigated by immunohistochemistry followed by morphometric quantification. The cross-sectional area and the expression of cytoskeletal proteins in the media were lower in restenotic lesions and, to a lesser extent, in stable plaques compared with mildly stenotic plaques and erosions. An important expression of α-SMA was detected in the intima of the different lesions; moreover, α-SMA staining was significantly larger in erosions compared with all other conditions. In the same location, a striking decrease of SMMHCs and a disappearance of smoothelin were observed in all situations. Conclusions— Medial atrophy is prevalent in restenotic lesions and stable plaques compared with mildly stenot...

107 citations


Journal ArticleDOI
TL;DR: It is reported that human bladder expresses VDR (determined by real-time PCR immunohistochemistry and Western blot) and responds to VDR agonists, such as the natural ligand, calcitriol, and its synthetic and less hypercalcemic derivative, BXL-628.
Abstract: Human prostate is now considered a target for vitamin D receptor (VDR) ligands, such as BXL-628. Because BXL-628 inhibited prostate growth without interfering with androgen signaling, it represents a new option for benign prostate hyperplasia (BPH) therapy. However, BPH symptoms are related not only to prostate size, but also to compensatory bladder hypertrophy and eventual overactivity. We now report that human bladder expresses VDR (determined by real-time PCR immunohistochemistry and Western blot) and responds to VDR agonists, such as the natural ligand, calcitriol, and its synthetic and less hypercalcemic derivative, BXL-628. Experiments were conducted with stromal cells derived from human bladder neck obtained at surgery from BPH patients. BXL-628 counteracted keratinocyte growth factor (KGF) and androgen-induced cell proliferation and stimulated apoptosis with a parallel reduced expression of the survival oncoprotein Bcl-2. Prolonged serum starvation time-dependently pushed bladder stromal cells to express activated myofibroblast markers, such as desmin and smoothelin, without changing other contractile-related proteins and intermediate filaments, such as vimentin. Chronic exposure to BXL-628 prevented starvation-induced cell phenotype modification. Because hypertrophy and starvation-induced bladder remodeling are supposed to underlie bladder overactivity, it is possible that BXL-628 might be helpful in reducing not only cumbersome symptoms related to prostate overgrowth, but also those related to bladder irritation.

103 citations


Journal ArticleDOI
TL;DR: It is concluded that absence of eNOS adversely affects UA remodeling in pregnancy, which may explain the impaired pregnancy outcome observed in these mice.
Abstract: The progressive rise in uterine blood flow during pregnancy is accompanied by outward hypertrophic remodeling of the uterine artery (UA). This process involves changes of the arterial smooth muscle cells and extracellular matrix. Acute increases in blood flow stimulate endothelial production of nitric oxide (NO). It remains to be established whether endothelial NO synthase (eNOS) is involved in pregnancy-related arterial remodeling. We tested the hypothesis that absence of eNOS results in a reduced remodeling capacity of the UA during pregnancy leading to a decline in neonatal outcome. UA of nonpregnant and pregnant wild-type (Nos3+/+) and eNOS-deficient (Nos3−/−) mice were collected and processed for standard morphometrical analyses. In addition, cross sections of UA were processed for cytological (smoothelin, smooth muscle α-actin) and proliferation (Ki-67) immunostaining. We compared the pregnancy-related changes longitudinally and, together with the data on pregnancy outcome, transversally by...

97 citations


Journal ArticleDOI
TL;DR: Both TA and PD cultures contain cells, presumably stem cells, that undergo osteogenic and myofibroblast differentiation, and may induce these processes by paracrine interactions.
Abstract: Tissue ossification in Peyronie disease (commonly known as Peyronie's disease [PD]), a localized fibrotic lesion within the tunica albuginea (TA) of the penis, may result from osteogenic differentiation of fibroblasts, myofibroblasts, and/or adult stem cells in the TA, and may be triggered by chronic inflammation, oxidative stress, and profibrotic factors like transforming growth factor beta 1 (TGFB1). In this study, we have investigated whether cultures of cells from normal TA and PD plaques undergo osteogenesis, express markers for stem cells, and originate other cell lineages via processes modulated by TGFB1. We found that TA and PD cells in osteogenic medium (OM) expressed osteogenic markers, alkaline phosphatase, and osteopontin and underwent calcification. PD cells, but not TA cells, formed foci in soft agar that were positive for alkaline phosphatase and calcification and expressed the mRNAs for osteoblast-specific factors pleiotrophin and periostin and bone morphogenic protein 2. Both cultures expressed stem cell marker CD34 antigen but not protein tyrosine phosphatase, receptor type c. TA and PD cells expressed smooth-muscle cell markers smoothelin and transgelin. None of the cultures underwent adipogenesis in adipogenic medium. Incubation with TGFB1 increased osteogenesis and myofibroblast differentiation and reduced CD34 antigen expression in both cultures. TA and PD cells modulated the differentiation of the multipotent C3H 10T(1/2) cells in dual cultures, into osteoblasts and myofibroblasts. In conclusion, both TA and PD cultures contain cells, presumably stem cells, that undergo osteogenic and myofibroblast differentiation, and may induce these processes by paracrine interactions. This may explain progression of fibrosis in the PD plaque and its eventual calcification.

84 citations


Journal ArticleDOI
TL;DR: Smoothelin-A is essential for functional contractility of intestinal smooth muscle and is reminiscent of that seen in patients with chronic intestinal pseudo-obstruction, and experimental data indicate a role for smoothelins in smooth muscle contraction.

74 citations


Journal ArticleDOI
TL;DR: The NVSMC show a distinct distribution that might reflect different aspects of their function in the choroid and suprachoroid, and all cells could be histochemically characterized as truly contractile.
Abstract: To characterize further non-vascular smooth muscle cells (NVSMC) in the choroid of the human eye, extensive morphological studies were performed including a three-dimensional distribution of NVSMC in the adult human eye and their appearance during development. Whole mounts and sections through the choroid and sclera of eyes of 42 human donors (between the 13th week of gestation and 89 years of age) were stained with antibodies against smooth muscle actin and other markers for smooth muscle cells. On the basis of their morphological localization, three groups of NVSMC could be distinguished in the adult eyes: (a) a semicircular arrangement of NVSMC in the suprachoroid and inner sclera, around the entry of posterior ciliary arteries and nerves; (b) NVSMC parallel to the vessels in the posterior eye segment between the point of entry of the posterior ciliary arteries and the point of exit of the vortex veins; and (c) a dense plaque-like arrangement of NVSMC in the suprachoroid, overlying the foveal region. The last of these groups showed most pronounced interindividual differences. During development, the first NVSMC to be observed at the 20th week of gestation belonged to group b. A complete NVSMC network was first observed in a 6-year-old donor eye. All three groups stained positive for smoothelin, caldesmon and calponin in all localizations. The NVSMC show a distinct distribution that might reflect different aspects of their function in the choroid and suprachoroid. All cells could be histochemically characterized as truly contractile.

66 citations


Journal ArticleDOI
TL;DR: Proteomic analysis of cancerous and noncancerous tissues from HCC patients with HCV infection determined that, in the cancerous tissues, HSP70 family proteins such as HSP60, α-enolase, phosphoglycerate mutase 1, ATP synthetase β chain and triosephosphate isomerase were increased whereas albumin, ferritin light chain, smoothelin and kietohexokinase were decreased.
Abstract: Chronic infection with hepatitis C virus (HCV) is known to be a risk factor for not only cirrhosis and steatosis but also hepatocellular carcinoma (HCC). A number of diagnostic and prognostic molecular markers are being identified by transcriptomic and proteomic analysis of HCC today. However, the analyses are performed on HCC in general, and the studied tissues are HCV infected, HBV infected, infected with both or neither, or the infection status may be unknown. The authors performed proteomic analysis of cancerous and noncancerous tissues from HCC patients with HCV infection, and determined that, in the cancerous tissues, HSP70 family proteins such as GRP78, HSC70, GRP75 and HSP70.1, glutaine synthetase isoforms, HSP60, alpha-enolase, phosphoglycerate mutase 1, ATP synthetase beta chain and triosephosphate isomerase were increased whereas albumin, ferritin light chain, smoothelin, tropomyosin beta chain, arginase 1, aldolase B and kietohexokinase were decreased. The aim of this study is to understand the pathogenesis of HCV-HCC using proteomic analysis of samples from HCV-HCC patients on which transcriptomics has already been performed.

52 citations


Journal ArticleDOI
TL;DR: The concept that the conceptus does not contribute to the initiation of UA remodeling of pregnancy is supported, and it is suggested that ovarian hormones trigger the onset ofUA remodeling.
Abstract: During pregnancy, the lumenal diameter and wall mass of the uterine artery (UA) increase, most likely in response to the increased hemodynamic strain resulting from the chronically elevated uterine blood flow (UBF). In this remodeling process, the phenotype of vascular smooth-muscle cells (VSMC) is transiently altered to enable VSMC proliferation. These phenomena are already seen during early pregnancy, when the rise in UBF is still modest. This raises the question whether the newly instituted endocrine environment of pregnancy is involved in the onset of the pregnancy-related UA remodeling. We tested the hypothesis that the conceptus is not essential for the onset of UA remodeling of pregnancy. Six control and 18 pseudopregnant (Postcopulation Days 5, 11, and 17; n = 6 per subgroup) C57Bl/6 mice were killed and UAs were dissected and processed for either morphometric analysis or immunohistochemistry. The latter consisted of staining UA cross sections for the differentiation markers smooth muscle alpha-actin and smoothelin, and for the proliferation marker MKI67. We analyzed the UA changes in response to pseudopregnancy by ANOVA. Data are presented as mean +/- SD. By Day 11 of pseudopregnancy, the UA lumen was 25% wider and the media cross-sectional area 71% larger than in control mice. These differences were accompanied by reduced smoothelin expression and increased proliferation of UA medial VSMC. All UA morphological differences had returned or were in the process of returning to baseline values by Day 17 of pseudopregnancy. The structural and cellular aspects of UA remodeling as seen at midpregnancy are also seen in pseudopregnancy. These results support the concept that the conceptus does not contribute to the initiation of UA remodeling. We suggest that ovarian hormones trigger the onset of UA remodeling.

44 citations


Journal ArticleDOI
TL;DR: The fraction of caverns containing the particular structural proteins studied and endothelial cell proliferation within caverns are not correlated with particular lesion features and clinical manifestations that were investigated in CCMs.
Abstract: OBJECTIVE Cerebral cavernous malformations (CCMs) are associated with hemorrhagic proliferation of endothelial-lined vascular caverns, resulting in hemorrhagic stroke, epilepsy, and other neurological manifestations. We hypothesize that structural protein expression and endothelial cell proliferation markers within CCM lesions are different in the setting of various clinical manifestations. METHODS The percentage of immunohistochemically stained caverns positive for collagen IV, fibronectin, laminin, alpha-smooth muscle actin, myosin, and smoothelin and the percentage of dividing endothelial cells within caverns were determined in 36 excised CCM surgical specimens. These were compared in CCMs with different multiplicity, location, and size in patients of different age, sex, seizure status, and hemorrhage status. RESULTS Comparisons of seven lesion features and clinical manifestations with the fraction of caverns containing the structural proteins studied and endothelial cell proliferation demonstrated no significant differences. A possible exception was the difference (P < 0.05) in the fraction (mean +/- standard deviation) of positively stained caverns for collagen IV between adult (0.63 +/- 0.39) and pediatric patients (0.87 +/- 0.21) as well as fewer caverns with laminin expression in older patients. These trends did not sustain significance with Bonferroni's correction for multiple comparisons. CONCLUSION The fraction of caverns containing the particular structural proteins studied and endothelial cell proliferation within caverns are not correlated with particular lesion features and clinical manifestations that were investigated in CCMs. The possible fewer fractions of caverns containing collagen IV and laminin in adult lesions compared with pediatric lesions may have implications for lesion regression and quiescence with age.

17 citations