Extrarenal angiomyolipoma in uterine cervix: rare presentation in unusual site

Angiomyolipoma is a benign neoplasm composed of variable admixture of blood vessels, smooth muscle cells and adipose tissue. Cervical angiomyolipoma are extremely rare and to the best of our knowledge only five cases of angiomyolipoma in cervix have been reported in the literature till date. Authors are presenting a case of angiomyolipoma arising from the uterine cervix. 43 years old female presented with mass descending per vagina for 6 months. This case had no association with tuberous sclerosis. Microscopic examination showed an ill-defined polypoidal, non-encapsulated lesion covered by keratinized stratified epithelium. The lesion is made up of three components, predominantly by fascicles of spindle shaped cells, varying sized blood vessels and multiple foci of mature adipocytes with no evidence of atypia or increased mitotic activity. Smooth muscle component showed strong immunoreactivity to SMA and absence of elastic fibres in the blood vessels were confirmed by histochemistry. Non-vascular smooth muscle cells were negative for HMB-45 in contrast to renal and other extra-renal angiomyolipoma in which HMB-45 immunoreactivity in seen in these cells. To conclude, the differential diagnosis of lower abdominal mass and dysfunctional uterine bleeding should include the angiomyolipoma, even though the uterine cervix is an extremely rare location where they occur.

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Immunogold localization of HMB-45 antigen in pulmonary lymphangiomyomatosis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141366 ◽

1995 ◽

Vol 53 ◽

pp. 998-999

Author(s):

J.M. Minda ◽

E. Dessy ◽

G. G. Pietra

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Room Temperature ◽

Osmium Tetroxide ◽

Muscle Cells ◽

Ultrastructural Localization ◽

Reproductive Age ◽

Thin Sections ◽

Smooth Muscle Proliferation ◽

Hmb 45

Pulmonary lymphangiomyomatosis (PLAM) is a rare disease occurring exclusively in women of reproductive age. It involves the lungs, lymph nodes and lymphatic ducts. In the lungs, it is characterized by the proliferation of smooth muscle cells around lymphatics in the bronchovascular bundles, lobular septa and pleura The nature of smooth muscle proliferation in PLAM is still unclear. Recently, reactivity of the smooth muscle cells for HMB-45, a melanoma-related antigen has been reported by immunohistochemistry. The purpose of this study was the ultrastructural localization of HMB-45 immunoreactivity in these cells using gold-labeled antibodies.Lung tissue from three cases of PLAM, referred to our Institution for lung transplantation, was embedded in either Poly/Bed 812 post-fixed in 1% osmium tetroxide, or in LR White, without osmication. For the immunogold technique, thin sections were placed on Nickel grids and incubated with affinity purified, monoclonal anti-melanoma antibody HMB-45 (1:1) (Enzo Diag. Co) overnight at 4°C. After extensive washing with PBS, grids were treated with Goat-anti-mouse-IgG-Gold (5nm) (1:10) (Amersham Life Sci) for 1 hour, at room temperature.

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Effect of all-trans retinoic acid and pentagalloyl glucose on smooth muscle cell elastogenesis

Bio-Medical Materials and Engineering ◽

10.3233/bme-201152 ◽

2021 ◽

pp. 1-13

Author(s):

Kaveh Sanaei ◽

Sydney Plotner ◽

Anson Oommen Jacob ◽

Jaime Ramirez-Vick ◽

Narendra Vyavahare ◽

...

Keyword(s):

Smooth Muscle ◽

Retinoic Acid ◽

Smooth Muscle Cells ◽

Blood Vessels ◽

Muscle Cells ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid ◽

Tissue Engineered Blood Vessels ◽

Pentagalloyl Glucose ◽

Vitamin A Derivative

BACKGROUND: The main objective of tissue engineering is to fabricate a tissue construct that mimics native tissue both biologically and mechanically. A recurring problem for tissue-engineered blood vessels (TEBV) is deficient elastogenesis from seeded smooth muscle cells. Elastin is an integral mechanical component in blood vessels, allowing elastic deformation and retraction in response to the shear and pulsatile forces of the cardiac system. OBJECTIVE: The goal of this research is to assess the effect of the vitamin A derivative all-trans retinoic acid (RA) and polyphenol pentagalloyl glucose (PGG) on the expression of elastin in human aortic smooth muscle cells (hASMC). METHODS: A polycaprolactone (PCL) and the gelatin polymer composite was electrospun and doped with RA and PGG. The scaffolds were subsequently seeded with hASMCs and incubated for five weeks. The resulting tissue-engineered constructs were evaluated using qPCR and Fastin assay for their elastin expression and deposition. RESULTS: All treatments showed an increased elastin expression compared to the control, with PGG treatments showing a significant increase in gene expression and elastin deposition.

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Differential Expression of Melanocytic Markers in Myoid, Lipomatous, and Vascular Components of Renal Angiomyolipomas

Archives of Pathology & Laboratory Medicine ◽

10.5858/2007-131-122-deommi ◽

2007 ◽

Vol 131 (1) ◽

pp. 122-125 ◽

Cited By ~ 1

Author(s):

Andres A. Roma ◽

Cristina Magi-Galluzzi ◽

Ming Zhou

Keyword(s):

Smooth Muscle ◽

Blood Vessel ◽

Blood Vessels ◽

Differential Expression ◽

Tumor Cells ◽

Tissue Microarray ◽

Expression Patterns ◽

Renal Angiomyolipoma ◽

Melanocytic Lesions ◽

Hmb 45

Abstract Context.—Renal angiomyolipoma is a tumor composed of varying amounts of fat, smooth muscle, and blood vessels. Characteristically, tumor cells express melanocytic markers such as HMB-45 and Melan-A. Recently, several other markers have been described as having excellent diagnostic sensitivity in cutaneous melanocytic lesions. Objectives.—To compare the sensitivities of 5 melanocytic markers in renal angiomyolipoma and to study the expression patterns of these markers in the 3 different components of angiomyolipoma. Design.—A tissue microarray of 20 renal angiomyolipomas was constructed. For each case, 3 cores containing fat, blood vessels, and smooth muscle were taken. The tissue microarray was then stained for HMB-45, Melan-A, tyrosinase, NK1-C3, and CD117. Results.—HMB-45 was positive in 95%, Melan-A in 85%, NK1-C3 in 70%, tyrosinase in 50%, and CD117 in 40% of the cases. All (20/20) were positive for HMB-45 and Melan-A combined. These 5 markers had different sensitivities in the 3 components. HMB-45 was positive in 90%, 85%, and 80% of fat, smooth muscle, and blood vessel components, respectively; Melan-A in 70%, 60%, and 40%; NK1-C3 in 55%, 55%, and 45%; tyrosinase in 30%, 40%, and 10%; and CD117 in 20%, 40%, and 10%, respectively, of these 3 components. Conclusions.—HMB-45 and Melan-A combined were positive in 100% of the renal angiomyolipomas. We recommend the use of these 2 markers in the workup of this entity, including those with predominantly 1 component. Other melanocytic markers are of limited use. A tissue block comprising predominantly fat or smooth muscle components should be used when performing melanocytic marker immunostain.

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Endothelial and Smooth Muscle Cells as Antagonists in Vascular Fibrinoysis

10.1055/s-0039-1689470 ◽

1975 ◽

Author(s):

V. Noordhoek Hegt

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Blood Vessels ◽

Plasminogen Activator ◽

Fibrinolytic Activity ◽

Vascular System ◽

Muscle Cells ◽

Vascular Wall ◽

Vasa Vasorum ◽

Slide Technique

Endothelial plasminogen activator activity in different types of human blood vessels obtained from fifty necropsies and thirty-five biopsies was detected and localized by means of plasminogen-rich fibrin slides. Great differences in endothelial activator activity were found along and across (vasa vasorum) the wall of the human vascular system.The same blood vessels were simultaneously investigated by a modified fibrin slide technique using plasminogen-free fibrin slides covered by plasmin to detect and localize inhibition of fibrinolysis in the vascular wall. The great variation in plasmin inhibition in different vessels revealed by this “fibrin slide sandwich technique” appeared to be closely associated with the localization and number of smooth muscle cells present in the walls of the vascular system. Strong plasmin inhibition was generally found at sites which showed no activator activity with the regular fibrin slide technique, while areas with a high endothelial fibrinolytic activity mostly revealed no inhibitory capacity.These results indicate that much of the variation in endothelial fibrinolytic activity on fibrin slides is due to inhibitory effects from the surrounding smooth muscle cells rather than to variability in the plasminogen activator content of the endothelium itself.

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Differentiation of Smooth Muscle Cells in Human Blood Vessels as Defined by Smoothelin, a Novel Marker for the Contractile Phenotype

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/01.atv.17.4.665 ◽

1997 ◽

Vol 17 (4) ◽

pp. 665-671 ◽

Cited By ~ 102

Author(s):

Frank T. L. van der Loop ◽

Giulio Gabbiani ◽

Gaby Kohnen ◽

Frans C. S. Ramaekers ◽

Guillaume J. J. M. van Eys

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Blood Vessels ◽

Human Blood ◽

Muscle Cells ◽

Contractile Phenotype

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Cyclic AMP-Rap1A signaling mediates cell surface translocation of microvascular smooth muscle α2C-adrenoceptors through the actin-binding protein filamin-2

AJP Cell Physiology ◽

10.1152/ajpcell.00221.2012 ◽

2013 ◽

Vol 305 (8) ◽

pp. C829-C845 ◽

Cited By ~ 22

Author(s):

Hanaa K. B. Motawea ◽

Selvi C. Jeyaraj ◽

Ali H. Eid ◽

Srabani Mitra ◽

Nicholas T. Unger ◽

...

Keyword(s):

Smooth Muscle ◽

Plasma Membrane ◽

Cyclic Amp ◽

Cell Surface ◽

Smooth Muscle Cells ◽

Blood Vessels ◽

Muscle Cells ◽

Small Gtpase ◽

Actin Binding ◽

Surface Translocation

The second messenger cyclic AMP (cAMP) plays a vital role in vascular physiology, including vasodilation of large blood vessels. We recently demonstrated cAMP activation of Epac-Rap1A and RhoA-Rho-associated kinase (ROCK)-F-actin signaling in arteriolar-derived smooth muscle cells increases expression and cell surface translocation of functional α2C-adrenoceptors (α2C-ARs) that mediate vasoconstriction in small blood vessels (arterioles). The Ras-related small GTPAse Rap1A increased expression of α2C-ARs and also increased translocation of perinuclear α2C-ARs to intracellular F-actin and to the plasma membrane. This study examined the mechanism of translocation to better understand the role of these newly discovered mediators of blood flow control, potentially activated in peripheral vascular disorders. We utilized a yeast two-hybrid screen with human microvascular smooth muscle cells (microVSM) cDNA library and the α2C-AR COOH terminus to identify a novel interaction with the actin cross-linker filamin-2. Yeast α-galactosidase assays, site-directed mutagenesis, and coimmunoprecipitation experiments in heterologous human embryonic kidney (HEK) 293 cells and in human microVSM demonstrated that α2C-ARs, but not α2A-AR subtype, interacted with filamin. In Rap1-stimulated human microVSM, α2C-ARs colocalized with filamin on intracellular filaments and at the plasma membrane. Small interfering RNA-mediated knockdown of filamin-2 inhibited Rap1-induced redistribution of α2C-ARs to the cell surface and inhibited receptor function. The studies suggest that cAMP-Rap1-Rho-ROCK signaling facilitates receptor translocation and function via phosphorylation of filamin-2 Ser2113. Together, these studies extend our previous findings to show that functional rescue of α2C-ARs is mediated through Rap1-filamin signaling. Perturbation of this signaling pathway may lead to alterations in α2C-AR trafficking and physiological function.

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ADP Receptor P2Y 12 Is Expressed in Vascular Smooth Muscle Cells and Stimulates Contraction in Human Blood Vessels

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/01.atv.0000142376.30582.ed ◽

2004 ◽

Vol 24 (10) ◽

pp. 1810-1815 ◽

Cited By ~ 128

Author(s):

Anna-Karin Wihlborg ◽

Lingwei Wang ◽

Oscar Östberg Braun ◽

Atli Eyjolfsson ◽

Ronny Gustafsson ◽

...

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Blood Vessels ◽

Vascular Smooth Muscle Cells ◽

Human Blood ◽

Muscle Cells ◽

Adp Receptor

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Different DNA methylome, transcriptome and histological features in uterine fibroids with and without MED12 mutations

10.21203/rs.3.rs-1041773/v1 ◽

2021 ◽

Author(s):

Ryo Maekawa ◽

Shun Sato ◽

Tetsuro Tamehisa ◽

Takahiro Sakai ◽

Takuya Kajimura ◽

...

Keyword(s):

Dna Methylation ◽

Extracellular Matrix ◽

Smooth Muscle ◽

Smooth Muscle Cells ◽

Blood Vessels ◽

Uterine Fibroids ◽

Muscle Cells ◽

Histological Features ◽

Dna Methylome

Abstract Background: Somatic mutations in Mediator complex subunit 12 (MED12m) have been reported as a biomarker of uterine fibroids (UFs). However, the role of MED12m is still unclear in the pathogenesis of UFs. Therefore, we investigated the differences in DNA methylome, transcriptome, and histological features between MED12m-positive and -negative UFs. Methods: DNA methylomes and transcriptomes were obtained from MED12m-positive and -negative UFs and myometrium, and hierarchically clustered. Differentially expressed genes in comparison with the myometrium and co-expressed genes detected by weighted gene co-expression network analysis were subjected to gene ontology enrichment analyses. The amounts of collagen fibers and the number of blood vessels and smooth muscle cells were histologically evaluated. Results: Hierarchical clustering based on DNA methylation clearly separated the myometrium, MED12m-positive, and MED12m-negative UFs. MED12m-positive UFs had the increased activities of extracellular matrix formation, whereas MED12m-negative UFs had the increased angiogenic activities and smooth muscle cell proliferation. Conclusion: The MED12m-positive and -negative UFs had different DNA methylation, gene expression, and histological features. The MED12m-positive UFs form the tumor with a rich extracellular matrix and poor blood vessels and smooth muscle cells compared to the MED12m-negative UFs, suggesting MED12 mutations affect the tissue composition of UFs.

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ADENINE NUCLEOTIDES AND THEREGULATION OF VASCULAR TONE

10.1055/s-0038-1643719 ◽

1987 ◽

Author(s):

J L Gordon

Keyword(s):

Endothelial Cells ◽

Smooth Muscle ◽

Smooth Muscle Cells ◽

Blood Vessels ◽

Vascular Tone ◽

Adenine Nucleotides ◽

Muscle Cells ◽

Vascular Endothelial ◽

Atp Analogs ◽

Vascular Beds

ATP, although known mainly as an intracellular energy source, is also capable of acting extracellularly as a vasoactive agent of great potency, at concentrations around lμM or less. ADP is approximately equipotent with ATP in its actions on extracellular receptors in the vasculature.ATP and ADP can arise extracellularly through release from the cytoplasm of cellsexposed to damaging stimuli or by degranulation of platelets. The concentration of the nucleotides in the cytoplasm of most cells (including vascular endothelial and smooth muscle cells) is more than ImM, and the concentration in the dense storage granules of platelets approaches 1M. Thus, there is potential for very high localised concentrations of ATP and ADP in the plasma following platelet degranulation or damageto cells of the vessel well. Release from vascular endothelial and smooth muscle cells can occur with no loss of cell viability or leakage of cytoplasmic proteins.The vasoactivity of ATP and ADP is mediated via P2 purinoceptors. Vasodilation can be induced through the release of EDRF from endothelial cells or through stimulation of PGI2 production (PGI2 is a vasodilator in many, althoughnot all, arterial beds). Purinoceptor-mediated prostacyclin production can be stimulated from perfused vascular beds (e.g. theheart andthe lung), from isolated blood vessels or from cultured endothelial cells.In some blood vessels, purinoceptor-mediated vasoconstriction can be induced by direct actionon the vascular smooth muscle cells. The receptors responsible are sub-classified as P2X (which induce vasoconstriction) and P2Y (whichinduce vasodilation). The P2Y purinoceptor that mediates EDRF production is very similar to that which is responsible for PGI2 production, although there are some intriguing differences inthe potency of ATP analogs at stimulating these two responses, even on the same cells. The intracellular mechanisms responsible have not yet been fully elucidated, but it appears that elevation of intracellular calcium is likely to play a causal role.Adenosine, which is the product of ATP and ADP metabolism by nucleotidases, can also induce vasodilation in many blood vessels, acting via P1] purinoceptors on the smooth muscle cells, but its potency is often less than that of ATP and ADP.The fate of adenine nucleotides released into the plasma is determined by ectonucleotidases on the luminal surface of the endothelial cells, not by enzymes in the blood itself (the half-life of ATP in samples of blood or plasma is many minutes, while in the microcirculation the half-life isless than one second). Endothelial ectonucleotidases have been detected in several vascular beds, and many of their characteristics are now known. These enzymes are distinct entities from the P2 purinoceptors on endothelium, as shown by the marked differences in potency of several ATP analogs as P2 receptor stimulants and as substrates for the nucleotidases.In summary, vascular endothelial and smooth muscle cells respond to extracellularATP and ADP, and can also metabolise thesenucleotides extracellularly by ectonucleotidases. In addition, ATP and ADP can be selectively released from the cells of the vessel wall and from activated platelets. Thus, the endothelial pericellular environment can be the site of complex interactions by which vascular tone is regulated through the release, actions and metabolism ofextracellular nucleotides.

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