Overproliferation Of Smooth Muscle Cells Research Articles

Nanotexture and crystal phase regulation for synergistic enhancement in re-endothelialization on medical pure titanium surface

Re-endothelialization has been recognized as a promising strategy to address the tissue hyperplasia and subsequent restenosis which are major complications associated with vascular implant/interventional titanium devices. However, the uncontrollable over-proliferation of smooth muscle cells (SMCs) limits the clinical application of numerous modified strategies. Herein, a novel modified strategy involving with a two-step anodic oxidation and annealing treatment was proposed to achieve rapid re-endothelialization function regulated by regular honeycomb nanotexture and specific anatase phase on the titanium surface. Theoretical calculation revealed that the presence of nanotexture reduced the polar component of surface energy, while the generation of anatase significantly enhanced the polar component and total surface energy. Meanwhile, the modified surface with regular nanotexture and anatase phase produced positive effect on the expression of CD31, VE-Cadherin and down-regulated α-SMA proteins expression, indicating excellent capacity of pro-endothelial regeneration and inhibition of SMCs proliferation and migration. One-month in vivo implantation in rabbit carotid arteries further confirmed that modified tube implant surface effectively accelerated confluent endothelial monolayer formation and promoted native-like endothelium tissue regeneration. By contrast, original titanium tube implant induced a disorganized tissue proliferation in the lumen with a high risk of restenosis. Collectively, this study opens us an alternative route to achieve the function that selectively promotes endothelial cells (ECs) growth and suppresses SMCs on the medical titanium surface, which has a great potential in facilitating re-endothelialization on the surface of blood-contacting titanium implant.

A review on developments of in-vitro and in-vivo evaluation of hybrid PCL-based natural polymers nanofibers scaffolds for vascular tissue engineering

The main objective of the present review article is to investigate the in-vitro and in-vivo biocompatibility behavior of hybrid PCL-based scaffolds with collagen, gelatin, and chitosan to improve endothelialization for VTE applications. It is reported that the high-rate failure of small diameters vascular grafts (SDVGs, <6 mm) due to adhesion of platelets and plasma protein and aggregation, over-proliferation of smooth muscle cells (SMCs), and neointimal hyperplasia at the implantation site is main challenge in vascular tissue engineering (VTE). The fast re-establishment of a functional endothelial cell (EC) layer representing a crucial importance strategy has been proposed to reduce these adverse outcomes. Polycaprolactone (PCL), with optimum mechanical properties, it showed great potential in biomedical applications, but its biocompatibility is still highly concerned in VTE. Modifications of the PCL vascular grafts by developing the hybrid structures using natural polymers with optimum hydrophilicity and biocompatibility properties in order to speed up the re-endothelialization process have been proposed over the last years. Analyzing the mentioned results in the present study can offer a better understanding of the benefits and challenges of applying the natural polymer as a thrombotic response upon implantation in clinical trials. Also, it can suggest the PCL-Collagen as the best framework for the fabrication of rationally designed SDVGs for VTE.

A nitric oxide-eluting and REDV peptide-conjugated coating promotes vascular healing

Drug-eluting stents (DESs) placement remarkably reduces the over-proliferation of smooth muscle cells (SMCs) and thus neointimal hyperplasia. However, the pharmacological agent also slows down the re-endothelization, delays injury vascular healing and increases the risk of in-stent restenosis (ISR). Here, inspired by mussel foot proteins (Mfps), a mimicking endothelium functional stent coating was efficiently fabricated by thiol-ene “click” reaction, consisting of catechol grafted chitosan (CS–C), zinc sulfate, and Arg-Glu-Asp-Val (REDV) peptide. The mimicking endothelium coating could continuously catalyze endogenous nitric oxide (NO) gas and maintain the bioactivity of REDV peptide. Compared with bare stents, the mimicking coatings significantly inhibited the acute thrombosis for the first 1-week, accelerated re-endothelization and decreased in-stent restenosis for 1- and 3-month after implantation. In addition, the synergistic effect of NO and REDV peptide also regulated inflammation response and promoted the expression of muscle fiber.

C-Abl regulates gastrointestinal muscularis propria homeostasis via ERKs

The gastrointestinal tract is responsible for food digestion and absorption. The muscularis propria propels the foodstuff through the GI tract and defects in intestine motility may cause obstruction disorders. Our present genetic studies identified non-receptor tyrosine kinase c-Abl as an important regulator of the muscularis propria homeostasis and a risk factor for rectal prolapse. Mouse deficient for c-Abl showed defects in the muscularis propria of gastrointestinal tract and older c-Abl−/− mice developed megaesophagus and rectal prolapse. Inhibition of c-Abl with imatinib mesylate, an anti-CML drug, or ablation of c-Abl using Prx1-Cre, which marks smooth muscle cells, recapitulated most of the muscularis propria phenotypes. The pathogenesis of rectal prolapse was attributable to overproliferation of smooth muscle cells, which was caused by enhanced ERK1/2 activation. Administration of ERK inhibitor U0126 impeded the development of rectal prolapse in c-Abl deficient mice. These results reveal a role for c-Abl-regulated smooth muscle proliferation in the pathogenesis of rectal prolapse, and imply that long-term use of imatinib mesylate may cause gastrointestinal problems in patients while ERK inhibitor may be effective in treating rectal prolapse.

Tropoelastin inhibits intimal hyperplasia of mouse bioresorbable arterial vascular grafts.

Small resorbable vascular grafts can block due to the over-proliferation of smooth muscle cells in neointimal hyperplasia. We show here that the proliferation of these cells is restricted in this type of graft. This is achieved with a simple dip, non-covalent coating of tropoelastin. It is in principle amendable to other grafts and is therefore an attractive process. This study is particularly significant because: (1) it shows that smooth muscle cell proliferation can be reduced while still accommodating the growth of endothelial cells, (2) small vascular grafts with an internal diameter of less than 1mm are amenable to this process, and (3) this process works for resorbable grafts.

MicroRNAs in Angiogenesis and Vascular Smooth Muscle Cell Function

The Human Genome Project was barely completed in 2003 before a new quest was launched: this time, in a search for short stretches of RNA called microRNA. The belief that these miniature molecules, which had only been discovered a decade earlier, were major regulators of genetic function gained momentum in the intervening years and sparked a worldwide interest in the physiologic and pathologic roles of microRNAs in the human body. These single-stranded, noncoding molecules of RNA, spanning to lengths of only 25 nucleotides, appear to modulate a range of cellular events by modifying the primary function of messenger RNA (mRNA): protein synthesis. The first regulatory RNA, lin-4, was discovered by Victor Ambros in 1993. Later, Andy Fire, Craig Mello, and David Baulcombe discovered small interfering RNA (siRNAs) and established the role of small noncoding mRNA in regulating cell function under a variety of conditions. The field has exploded in directions that no one could have predicted. We now know that small RNAs are expressed in most eukaryotic cells and regulate a remarkable number of cellular functions.1 The exact mechanism of action of microRNAs is unclear; however, it is believed that these molecules bind to select, noncoding regions of mRNA through traditional Watson and Crick base pairing, repressing or increasing expression of the genetic transcript and its corresponding protein. It is theorized that each molecule of microRNA regulates more than 100 distinct molecules of mRNA, with unknown but potentially far-reaching effects in the human body.2 Already multiple reports implicate an array of distinct microRNAs in cardiac and skeletal muscle myogenesis, apoptosis, regeneration, hypertrophy, fibrosis, and cardiac function. Investigators use microRNA expression profiling to identify specific microRNAs in a host of human and animal cells. Quantitative mass spectrometry measures protein levels in cells following the introduction of a specific microRNA …

Cystathionine gamma-lyase deficiency and overproliferation of smooth muscle cells

Cystathionine gamma-lyase (CSE)-derived H2S plays an important role in regulating cell growth. Lack of CSE expression results in development of hypertension. The current study compared proliferation of smooth muscle cells derived from CSE gene knockout mice (SMCs-KO) with that of wild-type mice (SMCs-WT). Cell proliferation was assessed by bromodeoxyuridine incorporation. Gene expression was analysed by western blotting, real-time PCR, and microarray analysis. Enhanced cell proliferation was detected in SMCs-KO and in the media of the aorta from CSE KO mice. SMCs-KO underwent significantly more apoptosis than SMCs-WT when treated with exogenous H2S (100 microM). CSE KO mice showed much lower level of phosphorylated extracellular signal-regulated kinase (ERK1/2) in mesentery arteries compared with those of WT mice, and exogenous H2S induced more phosphorylation of ERK1/2 in SMCs-KO compared with that in SMCs-WT. Decreased p21(Cip/WAF-1) but increased cyclin D1 expression was observed in isolated SMCs and vascular tissues from CSE KO mice, and exogenous H2S caused more increase in p21(Cip/WAF-1) expression and more decrease in cyclin D1 expression in SMCs-KO than in SMCs-WT. The transcriptional expression of calcitonin receptor-like, intergrin beta 1, and heparin-binding epidermal growth factor-like growth factor was also significantly increased in the aorta of CSE KO mice. SMCs-KO display an increased proliferation rate in vitro and in vivo, and these cells are more susceptible to apoptosis induced by exogenous H2S at physiologically relevant concentrations. These cellular effects of H2S are mediated by phosphorylation of ERK1/2 and altered expression of cyclin D1 and p21(Cip/WAF-1).

Enzymatic Release of a Surface‐Adsorbed RGD Therapeutic from a Cleavable Peptide Anchor

Means to attenuate this inflammatory response at the implantsite are of significant interest and currently include strategiesbased on surface morphology, chemical modification, or drugdelivery. This response is particularly evident at the site ofstent deployment, where the overproliferation of smoothmuscle cells can lead to restenosis—a re-narrowing of thelumen.

In atherogenesis, the apoptosis of endothelial cell itself could directly induce over-proliferation of smooth muscle cells

Over-proliferation of SMC (smooth muscle cell) is one characteristics of atherosclerosis. One well accepted mechanism is that the decrease of ECs (endothelial cells) induced by over apoptosis leads to endothelial dysfunction, which in turn results in over-proliferation of SMC. Obviously, the mechanism works after endothelial apoptosis. Compared with necrosis, apoptosis is time and energy consuming. The question is why the cell ends in the form of apoptosis instead of necrosis. From the evolutionary standpoint, apoptosis has some useful functions other than removing the damaged or unwanted cells. Recent studies showed that cells nearby the apoptotic ones began to proliferate and differentiate before apoptosis and the apoptotic signals could induce the near cells to proliferate without the death of cells. Apparently, some mechanism in apoptosis results in the proliferation of cells. So, we hypotheses that endothelial apoptosis can directly induce the over-proliferation of SMC.

Intrauterine growth restriction and the proliferation of smooth muscle cells in umbilical vessels

The purpose of this study was to investigate the proliferation of smooth muscle cells in umbilical vessels of fetuses affected by intrauterine growth restriction (IUGR) and to compare the findings with gestational age-matched control cases. Sixty umbilical cords from fetuses at 36-37 weeks gestation were examined. Fetuses were divided into three groups: group I, appropriate for dates birthweight; group II, IUGR with reassuring fetal status; and group III, IUGR with abnormal umbilical Doppler waveforms. Umbilical cords were immunostained with an antibody to proliferating cell nuclear antigen and Ki-67; stained smooth muscle cells were subsequently counted. Smooth muscle cell density was determined by counting the total number of cells in a representative area of vessel wall and the wall thickness of each vessel was also measured. Proliferation marker-positive cells were increased in the umbilical vessels of group II compared to group I, and there were more proliferating smooth muscle cells in the umbilical vessels of group III compared to the other two groups. The umbilical vessels of group III showed the highest smooth muscle cell density, but the wall thickness of all vessels was significantly thinner in group III than the other two groups. This study showed overproliferation of smooth muscle cells in the umbilical vessel walls associated with IUGR. It is hypothesised that hypoxia might induce this overproliferation given the further proliferation in IUGR fetuses with abnormal umbilical Doppler waveforms. Coexistence of a high cell density and lean vessel walls suggests small smooth muscle cells in umbilical vessels with IUGR.

Alport Syndrome with Diffuse Leiomyomatosis: When and When Not?

Alport Syndrome with Diffuse Leiomyomatosis: When and When Not?