Smooth Muscle Proliferation in Chronically Injured Canine Pulmonary Arteries Is Reduced by a Potent Platelet Aggregation Inhibitor U-53,059

1985 ◽  
Vol 53 (03) ◽  
pp. 351-355 ◽  
Author(s):  
Robert G Schaub ◽  
James C Keith ◽  
Carol A Simmons ◽  
Clarence A Rawlings
Keyword(s):  
Smooth Muscle ◽  
Platelet Aggregation ◽  
Dirofilaria Immitis ◽  
Leukocyte Adhesion ◽  
Pulmonary Arteries ◽  
Cell Loss ◽  
Endothelial Cell Loss ◽  
Dense Granules ◽  
Smooth Muscle Proliferation ◽  
Aggregation Inhibitor

Summary Dirofilaria immitis (DI) infection chronically injures canine pulmonary arteries. This injury produces endothelial cell loss, platelet/leukocyte adhesion, and smooth muscle proliferation. In the present study we assessed the effect of the cyclooxygenase inhibitor, U-53,059, on platelet function, platelet kinetics, coagulation, and smooth muscle proliferation in DI infected dogs.Platelet aggregation to the combination of arachidonic acid/ ADP was significantly inhibited by U-53,059. Coagulation and hematologic parameters were not effected by either DI infection or U-53,059 treatment. Platelet survival and the number of platelet dense granules were reduced in DI infection. Quantification of the lesions demonstrated that U-53,059 reduced both severity and density compared to non-treated dogs. U-53,059 is a potent and effective inhibitor of platelet aggregation which modifies smooth muscle proliferation produced by chronic vascular injury.

Vein Contraction And Smooth Muscle Cell Extensions As Causes Of Endothelial Sloughing During Graft Preparation

1981 ◽  
Author(s):  
F G Baumann ◽  
F P Catinella ◽  
J N Cunningham ◽  
F C Spencer
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Endothelial Cell ◽  
Vein Graft ◽  
Light Transmission ◽  
Autologous Blood ◽  
Cell Loss ◽  
Endothelial Cell Loss ◽  
Vein Wall ◽  
Luminal Diameter

In this study light, transmission and scanning electron microscopy were used to investigate the effects of various methods of vein graft preparation on endothelial and smooth muscle cells (SMC) of the dog cephalic vein. After removal, veins were stored in one of three heparinized solutions at 10°C for 5 minutes or 1 hour: autologous blood, Plasma-Lyte or Plasma-Lyte with 0.6 mg/ml Papaverine added. The vein wall proved very sensitive to dissection, manipulation and introduction of fixative and reacted to such stimuli with a severe contraction which not only diminished the luminal diameter, but also resulted in formation of medial SMC cytoplasmic extensions and protrusion of the endothelial cells into the lumen. The SMC cytoplasmic extensions were particularly frequent in the immediate subendothelial area and seem to play a role in lifting up, separating or desquamating the endothelial cells. Such findings also are relevant to the chronic effects of arterial spasm. Among the stored veins, those soaked in blood showed the greatest vessel wall contraction and endothelial cell loss. Veins soaked in Plasma-Lyte-Papaverine had the most relaxed and normal appearance and the least endothelial cell loss. If the Papaverine treated veins were subsequently subjected to brief distension at 100 mmHg, however, large gaps appeared between the endothelial lining cells. The results suggest that Papaverine treatment greatly reduces vein graft endothelial cell loss due to contraction, but Papaverine-induced relaxation should be reversed before the graft is subjected to arterial pressure.

Immunogold localization of HMB-45 antigen in pulmonary lymphangiomyomatosis

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.

ADP Plays a Key Role in Thrombogenesis in Rats

1988 ◽  
Vol 59 (02) ◽  
pp. 225-230 ◽  
Author(s):  
J P Maffrand ◽  
A Bernat ◽  
D Delebassée ◽  
G Defreyn ◽  
J P Cazenave ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Bleeding Time ◽  
Thrombus Formation ◽  
Vascular Wall ◽  
Cyclooxygenase Inhibitors ◽  
High Dose ◽  
Silk Thread ◽  
Dense Granules ◽  
Prolonged Bleeding Time ◽  
Venous Shunt

SummaryThe relative importance of ADP, arachidonic acid metabolites and serotonin as thrombogenic factors was evaluated in rats by comparing, after oral administration, the effects of two inhibitors of ADP-induced platelet aggregation (ticlopidine and PCR 4099), three cyclo-oxygenase inhibitors (aspirin, triflusal and indobufen) and a selective serotonin 5HT2 receptor antagonist (ketanserin) on platelet aggregation, in four platelet-dependent thrombosis models and on bleeding time. Platelet aggregation induced by ADP and collagen was completely inhibited by ticlopidine and PCR 4099 whereas only the collagen aggregation was reduced by the cyclo-oxygenase inhibitors. Ketanserin or a depletion of platelet serotonin by reserpine did not affect platelet aggregation. Ticlopidine and PCR 4099 greatly prolonged rat tail transection bleeding time. This is probably related to their known ability to inhibit ADP-mediated platelet aggregation. In contrast, the cyclooxygenase inhibitors did not affect bleeding time at all. Reserpine and ketanserin prolonged bleeding time by interfering with the action of serotonin on the vascular wall. Ticlopidine and PCR4099 were very potent antithrombotics in all the models. Aspirin, only at a high dose, inhibited poorly thrombus formation on a silk thread in an arterio-venous shunt, suggesting that the inhibition of cyclo-oxygenase was not responsible. Triflusal was inactive in all models while indobufen slightly reduced thrombus formation in the silk thread and metallic coil models. Ketanserin and reserpine reduced thrombus only in the metallic coil model. Thrombus formation was greatly reduced in fawn-hooded rats, which lack ADP in their platelet dense granules because of a genetic storage pool deficiency. Taken together, the results obtained with the drugs and with the fawn-hooded rats support the concept that ADP plays a key role in thrombogenesis in rats.

Medial Smooth Muscle Cell Proliferation in the Balloon Injured Rabbit Aorta: Effect of a Thiazole Compound with Platelet Inhibitory Activity

1984 ◽  
Vol 51 (01) ◽  
pp. 075-078 ◽  
Author(s):  
R G Schaub ◽  
C A Simmons
Keyword(s):  
Smooth Muscle ◽  
Platelet Aggregation ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Surface Characteristics ◽  
Inhibitory Effect ◽  
Lesion Size ◽  
Blue Staining ◽  
Morphologic Characteristics ◽  
Time Period

SummaryTwenty-seven adult male New Zealand rabbits (3–4 kgs) were used in this study. Six rabbits received vehicle, 3 groups of 6 each received doses of 4,5-bis(p-methoxyphenyl)-2-(trifluoromethyl)- thiazole, (U-53,059), at 0.3 mg/kg, 3.0 mg/kg and 30.0 mg/kg/day respectively. Drug and vehicle doses were given orally each day starting 3 days before balloon injury and continuing for the entire 2 week time period. Three rabbits were used as nontreated sham controls. In the vehicle and U-53,059 treated groups aortae were denuded of endothelial cells by balloon catheter injury. Two weeks after injury platelet aggregation to collagen was measured and the aortae removed for analysis of surface characteristics by scanning electron microscopy and lesion size by morphometry. All doses of U-53,059 inhibited platelet aggregation. The 3.0 and 30.0 mg/kg groups had the greatest inhibitory effect. All balloon injured aortae had the same morphologic characteristics. All vessels had similar extent and intensity of Evan’s blue staining, similar areas of leukocyte/platelet adhesion, and a myointimal cell cover of transformed smooth muscle cells. The myointimal proliferative response was not inhibited at any of the drug doses studied.

scholarly journals Influence of rebubbling on anterior segment parameters and refractive outcomes in eyes with DMEK for Fuchs endothelial dystrophy

2021 ◽  
Author(s):  
Bishr Agha ◽  
Raimund Forster ◽  
Thomas Kohnen ◽  
Ingo Schmack
Keyword(s):  
Visual Acuity ◽  
Endothelial Cell ◽  
Anterior Segment ◽  
Cell Loss ◽  
Endothelial Cell Loss ◽  
Refractive Outcome ◽  
Refractive Outcomes ◽  
Scheimpflug Imaging ◽  
Fuchs Endothelial Dystrophy ◽  
Anterior Segment Parameters

Abstract Purpose To evaluate the potential impact of rebubbling on the anterior segment parameters and refractive outcomes in patients with graft detachment following uneventful DMEK for Fuchs endothelial dystrophy (FED). Methods Retrospective institutional cohort study of comparing 34 eyes of 31 patients with rebubbling for graft detachment following Descemet membrane endothelial keratoplasty (DMEK) to 33 eyes of 28 patients with uneventful DMEK. Main outcome parameters were various corneal parameters obtained by Scheimpflug imaging, refractive outcome, corrected distance visual acuity (CDVA), and endothelial cell density (ECD). Results Anterior and posterior corneal astigmatism, corneal densitometry, central corneal thickness, and anterior chamber depth and volume showed no significant differences. Preoperative distribution of astigmatism axis orientations showed a high proportion of anterior corneal with-the-rule astigmatism (71%) in eyes requiring rebubbling. Mean postoperative cylinder in the rebubbling group (1.21 ± 0.85 D) was significantly higher compared to the controls (p = 0.04), while differences in spherical equivalent (SE) were insignificant (p = 0.24). Postoperative CDVA was 0.11 ± 0.11 in the control group compared to 0.21 ± 0.17 in the rebubbling group (p = 0.03). Eyes with subsequent rebubbling demonstrated a significantly higher endothelial cell loss (56% versus 37%) (p < 0.001). Conclusion Apart from higher cylinder values, refractive outcome and corneal parameters assessed by Scheimpflug imaging were comparable in eyes with rebubbling and controls. However, a reduced visual acuity and an increased endothelial cell loss should be taken into consideration prior to rebubbling especially in eyes with circumscribed graft detachment.

scholarly journals The Role of JAK/STAT Molecular Pathway in Vascular Remodeling Associated with Pulmonary Hypertension

2021 ◽  
Vol 22 (9) ◽  
pp. 4980
Author(s):  
Inés Roger ◽  
Javier Milara ◽  
Paula Montero ◽  
Julio Cortijo
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Vascular Remodeling ◽  
Pulmonary Arteries ◽  
Clinical Manifestations ◽  
Different Types ◽  
Artery Remodeling ◽  
Stat Pathway ◽  
Pulmonary Artery Remodeling

Pulmonary hypertension is defined as a group of diseases characterized by a progressive increase in pulmonary vascular resistance (PVR), which leads to right ventricular failure and premature death. There are multiple clinical manifestations that can be grouped into five different types. Pulmonary artery remodeling is a common feature in pulmonary hypertension (PH) characterized by endothelial dysfunction and smooth muscle pulmonary artery cell proliferation. The current treatments for PH are limited to vasodilatory agents that do not stop the progression of the disease. Therefore, there is a need for new agents that inhibit pulmonary artery remodeling targeting the main genetic, molecular, and cellular processes involved in PH. Chronic inflammation contributes to pulmonary artery remodeling and PH, among other vascular disorders, and many inflammatory mediators signal through the JAK/STAT pathway. Recent evidence indicates that the JAK/STAT pathway is overactivated in the pulmonary arteries of patients with PH of different types. In addition, different profibrotic cytokines such as IL-6, IL-13, and IL-11 and growth factors such as PDGF, VEGF, and TGFβ1 are activators of the JAK/STAT pathway and inducers of pulmonary remodeling, thus participating in the development of PH. The understanding of the participation and modulation of the JAK/STAT pathway in PH could be an attractive strategy for developing future treatments. There have been no studies to date focused on the JAK/STAT pathway and PH. In this review, we focus on the analysis of the expression and distribution of different JAK/STAT isoforms in the pulmonary arteries of patients with different types of PH. Furthermore, molecular canonical and noncanonical JAK/STAT pathway transactivation will be discussed in the context of vascular remodeling and PH. The consequences of JAK/STAT activation for endothelial cells and pulmonary artery smooth muscle cells’ proliferation, migration, senescence, and transformation into mesenchymal/myofibroblast cells will be described and discussed, together with different promising drugs targeting the JAK/STAT pathway in vitro and in vivo.

scholarly journals Comparison of Long-Term Outcomes of the Lamellar and Penetrating Keratoplasty Approaches in Patients with Keratoconus

2021 ◽  
Vol 10 (11) ◽  
pp. 2421
Author(s):  
Dominika Janiszewska-Bil ◽  
Barbara Czarnota-Nowakowska ◽  
Katarzyna Krysik ◽  
Anita Lyssek-Boroń ◽  
Dariusz Dobrowolski ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Adverse Events ◽  
Penetrating Keratoplasty ◽  
Corneal Thickness ◽  
Cell Loss ◽  
Lamellar Keratoplasty ◽  
Deep Anterior Lamellar Keratoplasty ◽  
Endothelial Cell Loss ◽  
Anterior Lamellar Keratoplasty ◽  
Significant Difference

We compared the visual and refractive outcomes, intraocular pressure (IOP), endothelial cell loss (ECL), and adverse events in keratoconus patients after deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK) with the best corrected visual acuity (BCVA) below 0.3 (logMAR 0.52). This is a prospective, comparative cohort study of 90 eyes (90 patients) with a clinical diagnosis of keratoconus. Patients underwent a complete eye examination before the surgical approach, 6 and 12 months postoperatively that consisted of BCVA, refractive astigmatism (AS), central corneal thickness (CCT), IOP, and ECL. Secondary outcomes were adverse events related to the surgical procedure. With lower ECL and less adverse events, DALK was revealed to be beneficial over PK with similar visual outcomes. Results: There was no significant difference between the BCVA in the DALK and PK groups (at 6 months: 0.49 ± 0.17 vs. 0.48 ± 0.17; p = 0.48; at 12 months: 0.54 ± 0.17 vs. 0.52 ± 0.14; p = 0.41). The mean value of AS was significantly lower after the PK procedure when compared to DALK, after both 6 and 12 months of follow up (p < 0.001). The CCT in the DALK group was significantly lower when compared to the PK group (at 6 months: 452.1 ± 89.1 µm vs. 528.9 ± 69.9 µm, p < 0.0001; at 12 months: 451.6 ± 83.5 µm vs. 525.5 ± 37.1 µm). The endothelial cell loss at 12 months after surgery was significantly lower after DALK when compared to PK (p < 0.0001). DALK transplantation should be considered as an alternative procedure in the surgical treatment of keratoconus.

scholarly journals Characterization of adenylyl cyclase isoforms in rat peripheral pulmonary arteries

2001 ◽  
Vol 280 (6) ◽  
pp. L1359-L1369 ◽  
Author(s):  
Karen B. Jourdan ◽  
Nicola A. Mason ◽  
Lu Long ◽  
Peter G. Philips ◽  
Martin R. Wilkins ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Adenylyl Cyclase ◽  
Pulmonary Arteries ◽  
Bronchial Epithelium ◽  
Rt Pcr ◽  
Bronchial Smooth Muscle ◽  
Functional Studies ◽  
Kinase C ◽  
Rat Lungs

Activation of adenylyl cyclase (AC), of which there are 10 diversely regulated isoforms, is important in regulating pulmonary vascular tone and remodeling. Immunohistochemistry in rat lungs demonstrated that AC2, AC3, and AC5/6 predominated in vascular and bronchial smooth muscle. Isoforms 1, 4, 7, and 8 localized to the bronchial epithelium. Exposure of animals to hypoxia did not change the pattern of isoform expression. RT-PCR confirmed mRNA expression of AC2, AC3, AC5, and AC6 and demonstrated AC7 and AC8 transcripts in smooth muscle. Western blotting confirmed the presence of AC2, AC3, and AC5/6 proteins. Functional studies provided evidence of cAMP regulation by Ca2+ and protein kinase C-activated but not Gi-inhibited pathways, supporting a role for AC2 and a Ca2+-stimulated isoform, AC8. However, NKH-477, an AC5-selective activator, was more potent than forskolin in elevating cAMP and inhibiting serum-stimulated [3H]thymidine incorporation, supporting the presence of AC5. These studies demonstrate differential expression of AC isoforms in rat lungs and provide evidence that AC2, AC5, and AC8 are functionally important in cAMP regulation and growth pathways in pulmonary artery myocytes.

scholarly journals Echistatin. A potent platelet aggregation inhibitor from the venom of the viper, Echis carinatus.

1988 ◽  
Vol 263 (36) ◽  
pp. 19827-19832 ◽  
Author(s):  
Z R Gan ◽  
R J Gould ◽  
J W Jacobs ◽  
P A Friedman ◽  
M A Polokoff
Keyword(s):  
Platelet Aggregation ◽  
Platelet Aggregation Inhibitor ◽  
Echis Carinatus ◽  
Aggregation Inhibitor

scholarly journals Complementary vasoactivity and matrix remodelling in arterial adaptations to altered flow and pressure

2008 ◽  
Vol 6 (32) ◽  
pp. 293-306 ◽  
Author(s):  
A Valentín ◽  
L Cardamone ◽  
S Baek ◽  
J.D Humphrey
Keyword(s):  
Smooth Muscle ◽  
Continuum Theory ◽  
Muscle Contractility ◽  
Smooth Muscle Contractility ◽  
Rates Of Change ◽  
Biomechanical Loading ◽  
Smooth Muscle Proliferation ◽  
And Function ◽  
Diverse Data ◽  
Induced Changes

Arteries exhibit a remarkable ability to adapt to sustained alterations in biomechanical loading, probably via mechanisms that are similarly involved in many arterial pathologies and responses to treatment. Of particular note, diverse data suggest that cell and matrix turnover within vasoaltered states enables arteries to adapt to sustained changes in blood flow and pressure. The goal herein is to show explicitly how altered smooth muscle contractility and matrix growth and remodelling work together to adapt the geometry, structure, stiffness and function of a representative basilar artery. Towards this end, we employ a continuum theory of constrained mixtures to model evolving changes in the wall, which depend on both wall shear stress-induced changes in vasoactive molecules (which alter smooth muscle proliferation and synthesis of matrix) and intramural stress-induced changes in growth factors (which alter cell and matrix turnover). Simulations show, for example, that such considerations help explain the different rates of experimentally observed adaptations to increased versus decreased flows as well as differences in rates of change in response to increased flows or pressures.

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