Proliferation Rate Of Smooth Muscle Cells Research Articles

The Effect of Long-Term Passage on Porcine SMCs' Function and the Improvement of TGF-β1 on Porcine SMCs' Secretory Function in Late Passage.

Cultured meat is one of the meat substitutes produced through tissue engineering and other technologies. Large-scale cell culture is the key for cultured meat products to enter the market. Therefore, this study is aimed to explore the effect of long-term passage in vitro on smooth muscle cells (SMCs) and the effect of transforming growth factor-β1 (TGF-β1) on SMCs in the late passage. Multiple passages lead to the decline of the proliferation rate of SMCs in the proliferation stage and the differentiation ability in the differentiation stage. Transcriptome results showed that the ECM pathway and aging-related signaling pathways were significantly up-regulated in the late passage period. TGF-β1 did not promote SMCs of late passage proliferation at the proliferation stage but promoted the gene and protein expression of collagen as the main protein of the extracellular matrix proteins at the differentiation stage. In addition, proteomic analysis revealed that TGF-β1 promoted the expression of cell adhesion molecules which activate the Hippo signaling pathway and the HIF-1 signaling pathway and further promoted the production of collagen-containing extracellular matrix proteins. This could provide ideas for large-scale production of cultured meat products using SMCs.

Quality evaluation of cultured meat with plant protein scaffold

Cultured meat technology is a promising new technology to solve the negative problems brought by traditional animal husbandry. Cultured meat should be further developed to appear on consumers' tables as alternative protein product. Therefore, this study used food grade peanut wire-drawing protein as scaffold to culture smooth muscle cells (SMCs) in vitro to obtain cultured meat productions containing both animal protein and plant protein. Multiple passages lead to the decline of the proliferation rate of SMCs in the proliferation stage and the differentiation ability in the differentiation stage, which means that the plasticity of cells decreased in the later stage of passage. SMCs can well adhere to the peanut wire-drawing protein scaffold and produce extracellular matrix protein and muscle protein, so as to form a cultured meat product with rich protein composition. This study provides a theoretical basis for the production of nutrient-rich cultured meat products.

Flow with variable pulse frequencies accelerates vascular recellularization and remodeling of a human bioscaffold.

Despite significant advances in vascular tissue engineering, the ideal graft has not yet been developed and autologous vessels remain the gold standard substitutes for small diameter bypass procedures. Here, we explore the use of a flow field with variable pulse frequencies over the regeneration of an ex vivo-derived human scaffold as vascular graft. Briefly, human umbilical veins were decellularized and used as scaffold for cellular repopulation with human smooth muscle cells (SMC) and endothelial cells (EC). Over graft development, the variable flow, which mimics the real-time cardiac output of an individual performing daily activities (e.g., resting vs. exercising), was implemented and compared to the commonly used constant pulse frequency. Results show marked differences on SMC and EC function, with changes at the molecular level reflecting on tissue scales. First, variable frequencies significantly increased SMC proliferation rate and glycosaminoglycan production. These results can be tied with the SMC gene expression that indicates a synthetic phenotype, with a significant downregulation of myosin heavy chain. Additionally and quite remarkably, the variable flow frequencies motivated the re-endothelialization of the grafts, with a quiescent-like structure observed after 10 days of conditioning, contrasting with the low surface coverage and unaligned EC observed under constant frequency (CF). Besides, the overall biomechanics of the generated grafts (conditioned with both pulsed and CFs) evidence a significant remodeling after 55 days of culture, depicted by high burst pressure and Young's modulus. These last results demonstrate the positive recellularization and remodeling of a human-derived scaffold toward an arterial vessel.

Pulmonary vascular remodeling is prior to the increase in pulmonary hypertension of chronic obstructive pulmonary disease

Objective: To explore the remodeling of pulmonary arterioles in chronic obstructive pulmonary disease (COPD), and its effect on hemorheology of proximal pulmonary arteries, right ventricular structure and function , and the potential mechanisms. Method: A total of 34 patients undergoing surgical treatment for lung tumors admitted to the General Hospital of Ningxia Medical University were included in the study. According to the preoperative lung function, there were 15 patients with COPD complicated with lung tumor (COPD group) and 19 patients with normal pulmonary function with lung tumor (control group). All patients underwent cardiac nuclear magnetic resonance (CMR) before surgery, and the hemorheology of the proximal pulmonary arteries, right ventricular structure and function were obtained by CMR. The normal lung tissues distal to the tumor lesion were taken during the operation, and the morphological changes of the pulmonary arterioles were observed by hematoxylin-eosin staining and Weigert-van Gieson. Immunohistochemistry was used to detect the location and expression of α-smooth muscle actin(SMA) and proliferating cell nuclear antigen(PCNA) in pulmonary arterioles, and the expression of protein and mRNA of α-SMA in lung tissue was detected by Western-blotting and real-time quantitative PCR. Results: The results of CMR showed that mPAP was not statistically different between COPD group and control group (24.0±3.7 vs 22.8±1.6, P>0.05). The main pulmonary artery distensibility (mPAD%), right ventricular myocardial mass end-diastolic (RVMED), right ventricular myocardial mass end-systolic (RVMES), average negative flow(ANF) and regurgitant fraction(RF%) were statistically different between COPD group and control group (P<0.05). The wall thickness (WT), WT% and WA% were significantly higher in COPD group [(37±18) μm, (65±19)% and (55±23)%, respectively] than in control group [(19±3 )μm, (29±5)% and (40±7)%, respectively]. The number of pulmonary arterial smooth muscle cells per unit area and smooth muscle cell proliferation rate were significantly higher in COPD group than in the control group(P<0.01). The expression of α-SMA protein and mRNA in COPD group was higher than that in control group(P<0.05). WA% and WT% were correlated inversely with mPAD%, but positively with RVMES, RVMED and RF%. Conclusions: Pulmonary vascular remodeling and rheological changes, even right heart myocardial structural changes, were observed in COPD patients without pulmonary arterial hypertension. Pulmonary arteriolar remodeling can affect the main pulmonary arterial hemorheology in COPD patients and further affect the myocardial structure of right heart. Pulmonary arterial remodeling may be a new direction for the clinical treatment of COPD.

Impact of electrospun Tecophilic/gelatin scaffold biofunctionalization on proliferation of vascular smooth muscle cells

Nanofibrous composite scaffolds based on Tecophilic (TP) and gelatin (gel) were electrospun and further modification of their surfaces was performed by adsorption of gelatin or fibronectin biomolecules. The ability of coated scaffolds to alter the proliferation rate of smooth muscle cells (SMCs) was investigated via various assays and compared to cell proliferation on non-coated scaffolds. The results confirmed the potential of both coated and non-coated composite scaffolds to support SMC growth. Although, the presence of fibronectin increased the proliferation, adsorbed gelatin could reduce the proliferation of SMCs. The success of a tissue engineered vascular graft depends on the ability of the scaffold to control the proliferation rate of SMCs and thus our study provides a better insight towards the fabrication of functional constructs for vascular regeneration.

Effect of extracellular signal-regulated kinase pathway on proliferation, phenotype and microRNA-31 expression on human arteriosclerotic smooth muscle cells

Objective To explore the effect of extracellular signal-regulated kinase (ERK), microRNA (miR)-31 and platelet derived growth factor (PDGF)-BB interaction on the proliferation of smooth muscle cells. Methods Lower extremity amputation from patients diagnosed as having ASO in Guangdong School of Medicine Affiliated Hospital was used for primary culture of smooth muscle cells. Cell counting kit-8 (CCK-8), Transwell, Western blotting, and real-time quantitative polymerase chain reaction (Real-time PCR) were used for evaluating PDGF-BB on the proliferation, migration and miR-31 expression on human VSMC cells. Results The tissue adherent method was used to successfully culture the original generation of arteriosclerosis smooth muscle cells. PDGF-BB enhanced proliferation rate of arteriosclerosis smooth muscle cells by 102% (P<0.05), and migration rate by 246% (P<0.05). PD98059 could block the effect of PDGF-BB, increasing the proliferation rate of smooth muscle cells by 53% (P<0.05), and migration rate by 19% (P<0.05). PDGF-BB could reduce shrinkage phenotypic marker protein α-smooth muscle actin (α-SMA) by 38% (P<0.05), but raise proliferative phenotypic marker protein of osteopontin (OPN) by 116% (P<0.05) and miR-31 by 386% (P<0.05). As compared with PDGF-BB group, treatment of PD98059 + PDGF-BB could significantly increase the α-SMA by 41% (P<0.05), but decrease the proliferative protein of OPN and miR-31 by 33% (P<0.05) and 46% respectively (P<0.05). Conclusion Blocking the ERK pathway can change vascular smooth muscule cells from proliferative to shrinkage phenotypic, and down-regulate miR-31 expression level at the same time. ERK-miR-31 pathway may be one of important pathways in regulating phenotype and function of human arteriosclerotic smooth muscle cells. Key words: Arteriosclerotic; Smooth muscle cells; Extracellular signal-regulated kinase; MicroRNA-31; Phenotype change

Abstract 489: Dual Role of Connexin37 in the Control of Vascular Inflammation and Smooth Muscle Cell Proliferation During Intimal Hyperplasia in Mice

Introduction: The long term patency of vascular interventions is plagued by restenosis due to intimal hyperplasia (IH). Intercellular communication mediated by gap junctions plays a key role in tissue homeostasis and we recently showed that the gap junction protein Connexin43 (Cx43) contributes to smooth muscle cell (SMC) proliferation and IH. We now hypothesized that vascular Cx37 also plays a role in vascular remodeling and IH. Methods and Results: WT and Cx37 deficient mice (Cx37-/-) were subjected to the carotid artery ligation model. In WT mice, the ligation resulted in IH formation, as evidence by the development of a SMC -rich neointima after two to four weeks. This remodeling correlated with a reduced Cx37 expression in the endothelium layer and an increased Cx37 expression in the media layer. Compared to WT mice, Cx37-/- mice displayed a delayed development of neointima due to reduced infiltration of CD45-positive immune cells. However, Cx37-/- mice displayed an accelerated SMC proliferation rate between two and four weeks post surgery, as evidence by the number of PCNA-positive cells. Cx37-/- mouse arteries overexpressed synthetic SMC markers. Finally, in primary human vein SMC, Cx37 overexpression reduced cell proliferation and migration. Conclusions: Cx37 plays a dual role in neointima formation following vascular injury. Cx37 promotes immune cell infiltration and inflammation in the vessel. On the other hand, Cx37 overexpression in SMC counteracts the proliferative role of Cx43. Thus, Cx37 may play both protective and harmful roles in IH.

Geometric, Hemodynamic, and Pathological Study of a Distal Internal Carotid Artery Aneurysm Model in Dogs

We created a distal internal carotid artery side-wall aneurysm model in dogs and compared its geometric, hemodynamic, and histological similarities with human models. Eight distal internal carotid artery-shaped devices were constructed using rapid prototyping, and 8 aneurysms were created via surgical reconstruction and elastase incubation. The geometric and hemodynamic parameters of the aneurysm and the parent artery of the dog and human models were compared, and histological response was evaluated at 12 weeks. Eight aneurysms were successfully created with good geometric simulation of the arteries between the dog and human models. Hemodynamic analysis revealed similar changes in the hemodynamic parameters both in the aneurysm sac and in the parent artery of the dog and human models. Histological analysis revealed internal elastic lamina discontinuity, elastic fiber disruption, a thinner muscular layer, increased smooth muscle cell proliferation rate, increased inflammation cell infiltration, and higher matrix metalloproteinase-2 and matrix metalloproteinase-9 expression indices in the medial aneurysm wall. The distal internal carotid artery aneurysm model in dogs is feasible and exhibited considerable geometric, hemodynamic, and histological similarities with the original human models.

Effects of Pulsatile Bioreactor Culture on Vascular Smooth Muscle Cells Seeded on Electrospun Poly (lactide‐co‐ε‐caprolactone) Scaffold

Electrospun nanofibrous scaffolds have several advantages, such as an extremely high surface-to-volume ratio, tunable porosity, and malleability to conform over a wide variety of sizes and shapes. However, there are limitations to culturing the cells on the scaffold, including the inability of the cells to infiltrate because of the scaffold's nano-sized pores. To overcome the limitations, we developed a controlled pulsatile bioreactor that produces static and dynamic flow, which improves transfer of such nutrients and oxygen, and a tubular-shaped vascular graft using cell matrix engineering. Electrospun scaffolds were seeded with smooth muscle cells (SMCs), cultured under dynamic or static conditions for 14 days, and analyzed. Mechanical examination revealed higher burst strength in the vascular grafts cultured under dynamic conditions than under static conditions. Also, immunohistology stain for alpa smooth muscle actin showed the difference of SMC distribution and existence on the scaffold between the static and dynamic culture conditions. The higher proliferation rate of SMCs in dynamic culture rather than static culture could be explained by the design of the bioreactor which mimics the physical environment such as media flow and pressure through the lumen of the construct. This supports regulation of collagen and leads to a significant increase in tensile strength of the engineered tissues. These results showed that the SMCs/electrospinning poly (lactide-co-ε-caprolactone) scaffold constructs formed tubular-shaped vascular grafts and could be useful in vascular tissue engineering.

A highly flexible paclitaxel-loaded poly(ε-caprolactone) electrospun fibrous-membrane-covered stent for benign cardia stricture

In benign esophageal strictures, inflammation reaction and tissue hyperplasia after stent placement greatly limit the stent retention time and affect subsequent scar formation, which is one of the main influences on long-term recurrence rate. A newly developed biodegradable electrospun drug-fiber-coated stent (DFCS) was fabricated to inhibit inflammation and scar formation. The electrospun paclitaxel/poly(ε-caprolactone) (PCL) fibers integrally covered the bare stent using the rotating collection method. The paclitaxel entrapment did not significantly affect the physical properties of electrospun PCL fibrous membranes. The mechanical results demonstrated that electrospun fibers containing paclitaxel covering the stent maintained the original mechanical characteristics of the stent, and no membrane tearing or ablation was observed after hundreds of repeated compressions. Paclitaxel release profiles were controlled mainly via diffusion of drug through the drug content, and stable release of paclitaxel continued up to 32days at pH 4.0. Higher inhibition of smooth muscle cell proliferation rates was observed on fibrous membranes with higher paclitaxel content. DFCS showed a significant decrease in tissue inflammation and collagen fiber proliferation, and was easily removed from the esophageal part, which had almost no damage to the tissues in the dog model. Therefore, DFCSs may have great potential to markedly attenuate stent-induced inflammation and scar formation in esophageal stenosis therapy.

Regulation of arginase pathway in response to wall shear stress

ObjectiveAlterations of wall shear stress can predispose the endothelium to the development of atherosclerotic plaques. Ample evidence indicates that arginase expression and/or activity correlates with several risk factors for cardiovascular disease including atherosclerosis. We investigated the regulation of arginase pathway in response to distinct patterns of wall shear stress. MethodsIsolated porcine endothelial cells and carotid arterial segments were perfused under unidirectional high shear stress (HSS) or oscillatory shear stress (OSS) for 1 and 3 days. Arginase I and II expression, cellular localization and enzyme activity were, respectively, assessed by Western blot, immunohistochemistry and colorimetric determination of urea. The contribution of arginase to the processes of endothelial dysfunction, cell proliferation and arterial remodeling induced by OSS was evaluated by administration of the arginase inhibitor N-ω-hydroxy-nor-l-arginine (nor-Noha). ResultsOnly arginase II isoform was detected on porcine carotid endothelial cells and on carotid artery. Exposure of arteries to OSS increased arginase II expression and activity as compared to HSS. Inhibition of arginase by nor-Noha improved NO-dependent endothelial function and decreased total vascular ROS formation in arteries submitted to OSS. In addition, inhibition of arginase activity decreased smooth muscle cell proliferation rate with no effect on collagen content after OSS. ConclusionsExposure of carotid artery to oscillatory flow induced a more pronounced activation of arginase as compared to HSS. Inhibition of arginase in arteries exposed to OSS improved NO-dependent endothelial function and decrease smooth muscle cell proliferation rate, both processes are important for the focal development of atherosclerotic plaque.

Prenatal Exposure to Fluoxetine Induces Fetal Pulmonary Hypertension in the Rat

Fluoxetine is a selective serotonin reuptake inhibitor antidepressant widely used by pregnant women. Epidemiological data suggest that fluoxetine exposure prenatally increases the prevalence of persistent pulmonary hypertension syndrome of the newborn. The mechanism responsible for this effect is unclear and paradoxical, considering the current evidence of a pulmonary hypertension protective fluoxetine effect in adult rodents. To evaluate the fluoxetine effect on fetal rat pulmonary vascular smooth muscle mechanical properties and cell proliferation rate. Pregnant rats were treated with fluoxetine (10 mg/kg) from Day 11 through Day 21 of gestation. Fetuses were delivered by cesarean section. As compared with controls, fluoxetine exposure resulted in fetal pulmonary hypertension as evidenced by an increase in the weight ratio of the right ventricle to the left ventricle plus septum (P = 0.02) and by an increase in pulmonary arterial medial thickness (P < 0.01). Postnatal mortality was increased among experimental animals, and arterial oxygen saturation was 96 +/- 1% in 1-day-old control animals and significantly lower (P < 0.01) in fluoxetine-exposed pups (79 +/- 2%). In vitro, fluoxetine induced pulmonary arterial muscle contraction in fetal, but not adult, animals (P < 0.01) and reduced serotonin-induced contraction at both ages (P < 0.01). After in utero exposure to a low fluoxetine concentration the pulmonary arterial smooth muscle cell proliferation rate was significantly increased in fetal, but not adult, cells (P < 0.01). In contrast to the adult, fluoxetine exposure in utero induces pulmonary hypertension in the fetal rat as a result of a developmentally regulated increase in pulmonary vascular smooth muscle proliferation.

Control of smooth muscle cell proliferation by ferrous iron

This study was conducted to determine the interaction of individual corrosion products from biodegradable iron stents with cells from the adjacent tissue. The response of human umbilical venous smooth muscle cells (SMCs) to an excess of ferrous ions was investigated in a cell culture model at the phenotypic and at the molecular level. When soluble ferrous ions were added to the cell culture medium the cell growth rate was reduced. Gene expression profiling indicated a reduction in the amounts of mRNA from genes that are required for cell proliferation. In addition, mRNA was regulated from multiple genes involved in iron homeostasis, DNA replication and lipid metabolism. In conclusion, ions released from iron stents could reduce the vascular SMC proliferation rate by influencing growth-related gene expression and may therefore play a beneficial role in antagonizing restenosis in vivo.

Aligned biodegradable nanofibrous structure: a potential scaffold for blood vessel engineering

A unique biodegradable nanofibrous structure, aligned poly( l-lactid- co- ε-caprolactone) [P(LLA-CL)] (75:25) copolymer nanofibrous scaffold was produced by electrospinning. The diameter of the generated fibers was around 500 nm with an aligned topography which mimics the circumferential orientation of cells and fibrils found in the medial layer of a native artery. A favorable interaction between this scaffold with human coronary artery smooth muscle cells (SMCs) was demonstrated via MTS assay, phase contrast light microscopy, scanning electron microscopy, immunohistology assay and laser scanning confocal microscopy separately. Tissue culture polystyrene and plane solvent-cast P(LLA-CL) film were used as controls. The results showed that, the SMCs attached and migrated along the axis of the aligned nanofibers and expressed a spindle-like contractile phenotype; the distribution and organization of smooth muscle cytoskeleton proteins inside SMCs were parallel to the direction of the nanofibers; the adhesion and proliferation rate of SMCs on the aligned nanofibrous scaffold was significantly improved than on the plane polymer films. The above results strongly suggest that this synthetic aligned matrix combines with the advantages of synthetic biodegradable polymers, nanometer-scale dimension mimicking the natural ECM and a defined architecture replicating the in vivo-like vascular structure, may represent an ideal tissue engineering scaffold, especially for blood vessel engineering.

Regulation of vascular smooth muscle cells by micropatterning

Vascular smooth muscle cells (SMCs) undergo morphological and phenotypic changes when cultured in vitro. To investigate whether SMC morphology regulates SMC functions, bovine aortic SMCs were grown on micropatterned collagen strips (50-, 30-, and 20-μm wide). The cell shape index and proliferation rate of SMCs on 30- and 20-μm strips were significantly lower than those on non-patterned collagen (control), and the spreading area was decreased only for cells patterned on the 20-μm strips, suggesting that SMC proliferation is dependent on cell shape index. The formation of actin stress fibers and the expression of α-actin were decreased in SMCs on the 20- and 30-μm collagen strips. SMCs cultured on micropatterned biomaterial poly-( d, l-lactide-co-glycolide) (PLGA) with 30-μm wide grooves also showed lower proliferation rate and less stress fibers than SMCs on non-patterned PLGA. Our findings suggest that micropatterned matrix proteins and topography can be used to control SMC morphology and that elongated cell morphology decreases SMC proliferation but is not sufficient to promote contractile phenotype.

Gamma-Irradiation Markedly Inhibits the Hydrated Collagen Gel Contraction by Arterial Smooth Muscle Cells

BackgroundVessel wall responses to percutaneous transluminal coronary angioplasty include neointimal proliferation and arterial remodeling. The contraction of a collagen gel is a good in vitro model of wound repair and...

Smooth muscle cell proliferation in the ductus arteriosus and the descending aorta, and effects of enalapril on SMC proliferation in perinatal rats.

This study was carried out to determine the proliferation profile of the smooth muscle cells (SMC) in the media of the ductus arteriosus (DA) and the descending aorta (Ao), and to examine the effects of the angiotensin-converting enzyme inhibitor enalapril on the proliferation of these cells in perinatal rats. The proliferating cell nuclear antigen (PCNA) index of the DA peaked in 19-day-old fetuses at 75%, and the index significantly declined in 20-day-old fetuses. The PCNA index of the Ao showed a similar profile until pups reached 1 day of age; however, the index of the Ao then increased in 3-day-old pups. The PCNA indices of the DA and Ao decreased significantly after maternal oral treatment with enalapril (10 mg/kg for 7 days), with a more marked decline in the DA than in the Ao. The PCNA indices of these vessels in 20-day-old fetuses were not altered by maternal treatment with enalapril. These results indicate that the SMC proliferation rate in the DA was similar to that in the Ao until pups reached the age of 1 day, and that the inhibitory effect of enalapril on the SMC proliferation was age-dependent and more prominent in the DA than in the Ao.

Flow modulates endothelial regulation of smooth muscle cell proliferation: A new model

Background: With a co-culture model, we have previously demonstrated that endothelial cells (ECs) exert regulatory control over smooth muscle cell (SMC) behavior. ECs appeared to stimulate SMC proliferation in static culture. This study was performed to test the hypothesis that the EC stimulation of SMC proliferation was effected by shear stress. Methods: Bovine SMCs were cultured on a thin semipermeable membrane either alone or opposite ECs in co-culture (SMC/EC). A novel parallel-plate flow device was developed and used for exposing the EC side of the co-culture to shear stress. EC and SMC proliferation rates were determined after 24 hours' exposure to 0, 1, or 10 dynes/cm 2 of shear stress. Results: SMC proliferation decreased significantly from 362 ± 65 cpm/μg DNA (control, mean ± SEM) to 68 ± 43 cpm/μg (1 dyne/cm 2) and 99 ± 18 cpm/μg (10 dynes/cm 2) ( P < .05). EC proliferation after flow decreased as compared with no-flow controls 71 ± 15 cpm/μg DNA (control, mean ± SEM) to 29 ± 5 cpm/μg (1 dyne/cm 2) and 21 ± 4 cpm/μg (10 dynes/cm 2) ( P < .05). Conclusions: In a model designed to study SMC/EC interactions in a flow environment, it was seen that EC exposure to shear stress alters the growth characteristics of SMCs. This suggests that hemodynamic mechanical forces may be sufficient to alter the EC regulation of SMC behavior. (Surgery 1998;124:353-61.)

Flow modulates endothelial regulation of smooth muscle cell proliferation: A new model

<h2>Abstract</h2> <b>Background:</b> With a co-culture model, we have previously demonstrated that endothelial cells (ECs) exert regulatory control over smooth muscle cell (SMC) behavior. ECs appeared to stimulate SMC proliferation in static culture. This study was performed to test the hypothesis that the EC stimulation of SMC proliferation was effected by shear stress. <b>Methods:</b> Bovine SMCs were cultured on a thin semipermeable membrane either alone or opposite ECs in co-culture (SMC/EC). A novel parallel-plate flow device was developed and used for exposing the EC side of the co-culture to shear stress. EC and SMC proliferation rates were determined after 24 hours' exposure to 0, 1, or 10 dynes/cm² of shear stress. <b>Results:</b> SMC proliferation decreased significantly from 362 ± 65 cpm/μg DNA (control, mean ± SEM) to 68 ± 43 cpm/μg (1 dyne/cm²) and 99 ± 18 cpm/μg (10 dynes/cm²) (<i>P</i> < .05). EC proliferation after flow decreased as compared with no-flow controls 71 ± 15 cpm/μg DNA (control, mean ± SEM) to 29 ± 5 cpm/μg (1 dyne/cm²) and 21 ± 4 cpm/μg (10 dynes/cm²) (<i>P</i> < .05). <b>Conclusions:</b> In a model designed to study SMC/EC interactions in a flow environment, it was seen that EC exposure to shear stress alters the growth characteristics of SMCs. This suggests that hemodynamic mechanical forces may be sufficient to alter the EC regulation of SMC behavior. (Surgery 1998;124:353-61.)

Aspirin enhances platelet-derived growth factor-induced vascular smooth muscle cell proliferation

Aspirin is frequently used after vascular reconstruction to pharmacologically prevent graft occlusion and to suppress the development of myointimal hyperplasia in vascular surgery, but its efficacy is controversial. The purpose of this study was to examine the direct effects of aspirin on platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell (SMC) proliferation. Human aortic SMCs were grown to confluence in 96 well plates. 3 x 10(-5) mol/L aspirin was added 24 hours previously and PDGF 10 ng/ml at the beginning of each experiment. Cell proliferation at 48 hours was determined using tritiated thymidine uptake. Supernatant 12-L-hydroxy 5,8,10,14-eicosatetraenoic acid (12-HETE) and prostaglandin E2 (PGE2) were measured by competitive enzyme immunoassay. Aspirin did not change vascular SMC proliferation rates relative to controls (4665 +/- 181 counts per minute [CPM] vs 4749 +/- 155 CPM). However, aspirin pretreatment of PDGF-stimulated vascular SMCs increased proliferation (9408 +/- 237 CPM vs 7283 +/- 283 CPM; p < 0.001). 5,8,10,14-eicosatriynoic acid, a 12-lipoxygenase inhibitor, decreased basal (2037 +/- 181 CPM vs 2306 +/- 158 CPM; p < 0.05) and PDGF-stimulated vascular SMC proliferation (4909 +/- 1089 CPM vs 4310 +/- 1022 CPM; p < 0.001). Aspirin increased supernatant 12-HETE levels and decreased PGE2 levels in both basal and PDGF-stimulated cell cultures. Aspirin enhances PDGF-stimulated vascular SMC proliferation. The effects of aspirin on vascular SMC proliferation may be mediated by changes in vascular SMC arachidonic acid metabolism.