Pulmonary hypertension is a complex and heterogeneous condition with five main subtypes (groups). This review focuses on pulmonary hypertension caused by chronic hypoxia (hypoxic pulmonary hypertension, HPH, group 3). It is based mainly on our own experimental work, especially our collaboration with the group of Professor Herget, whose fifth anniversary of death we commemorate. We have found that oxidation and degradation of the extracellular matrix (ECM) in vitro, in either the presence or the absence of pro-inflammatory cells, activate vascular smooth muscle cell (VSMC) proliferation. Significant changes in the ECM of pulmonary arteries also occurred in vivo in hypoxic rats, namely a decrease in collagen VI and an increase in matrix metalloproteinase 9 (MMP-9) in the tunica media, which may also contribute to the growth activation of VSMCs. The proliferation of VSMCs was also enhanced in their co-culture with macrophages, most likely due to the paracrine production of growth factors in these cells. However, hypoxia itself has a dual effect: on the one hand, it can activate VSMC proliferation and hyperplasia, but on the other hand, it can also induce VSMC hypertrophy and increased expression of contractile markers in these cells. The influence of hypoxia-inducible factors, microRNAs and galectin-3 in the initiation and development of HPH, and the role of cell types other than VSMCs (endothelial cells, adventitial fibroblasts) are also discussed. Keywords: Vasoconstriction, Remodeling, Oxidation, Degradation, Extracellular matrix, Collagen, Proteolytic enzymes, Metalloproteinases, Macrophages, Mast cells, Smooth muscle cells, Endothelial cells, Fibroblasts, Mesenchymal stem cells, Hypoxia-inducible factor, microRNA, Galectins, Hyperplasia, Hypertrophy, Therapy of hypoxic pulmonary hypertension.

• MeSH
• Hypoxia * metabolism   MeSH
• Humans MeSH
• Myocytes, Smooth Muscle * metabolism   pathology   MeSH
• Hypertension, Pulmonary * metabolism   pathology   MeSH
• Cell Proliferation MeSH
• Muscle, Smooth, Vascular * metabolism   pathology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Cell colonization of synthetic polymers can be regulated by physical and chemical modifications of the polymer surface. High-density and low-density polyethylene (HDPE and LDPE) were therefore activated with Ar⁺ plasma and grafted with fibronectin (Fn) or bovine serum albumin (BSA). The water drop contact angle usually decreased on the plasma-treated samples, due to the formation of oxidized groups, and this decrease was inversely related to the plasma exposure time (50-300 s). The presence of nitrogen and sulfur on the polymer surface, revealed by X-ray photoelectron spectroscopy (XPS), and also by immunofluorescence staining, showed that Fn and BSA were bound to this surface, particularly to HDPE. Plasma modification and grafting with Fn and BSA increased the nanoscale surface roughness of the polymer. This was mainly manifested on HDPE. Plasma treatment and grafting with Fn or BSA improved the adhesion and growth of vascular smooth muscle cells in a serum-supplemented medium. The final cell population densities on day 6 after seeding were on an average higher on LDPE than on HDPE. In a serum-free medium, BSA grafted to the polymer surface hampered cell adhesion. Thus, the cell behavior on polyethylene can be modulated by its type, intensity of plasma modification, grafting with biomolecules, and composition of the culture medium.

• Keywords
• albumin, bioactivity, biocompatibility, cell spreading area, fibronectin, nanoscale surface roughness, plasma treatment, tissue engineering, wettability,
• Publication type
• Journal Article MeSH

Intrinsic nanocrystalline diamond (NCD) films have been proven to be promising substrates for the adhesion, growth and osteogenic differentiation of bone-derived cells. To understand the role of various degrees of doping (semiconducting to metallic-like), the NCD films were deposited on silicon substrates by a microwave plasma-enhanced CVD process and their boron doping was achieved by adding trimethylboron to the CH(4):H(2) gas mixture, the B∶C ratio was 133, 1000 and 6700 ppm. The room temperature electrical resistivity of the films decreased from >10 MΩ (undoped films) to 55 kΩ, 0.6 kΩ, and 0.3 kΩ (doped films with 133, 1000 and 6700 ppm of B, respectively). The increase in the number of human osteoblast-like MG 63 cells in 7-day-old cultures on NCD films was most apparent on the NCD films doped with 133 and 1000 ppm of B (153,000 ± 14,000 and 152,000 ± 10,000 cells/cm(2), respectively, compared to 113,000 ± 10,000 cells/cm(2) on undoped NCD films). As measured by ELISA per mg of total protein, the cells on NCD with 133 and 1000 ppm of B also contained the highest concentrations of collagen I and alkaline phosphatase, respectively. On the NCD films with 6700 ppm of B, the cells contained the highest concentration of focal adhesion protein vinculin, and the highest amount of collagen I was adsorbed. The concentration of osteocalcin also increased with increasing level of B doping. The cell viability on all tested NCD films was almost 100%. Measurements of the concentration of ICAM-1, i.e. an immunoglobuline adhesion molecule binding inflammatory cells, suggested that the cells on the NCD films did not undergo significant immune activation. Thus, the potential of NCD films for bone tissue regeneration can be further enhanced and tailored by B doping and that B doping up to metallic-like levels is not detrimental for cells.

• MeSH
• Adsorption MeSH
• Boron chemistry   MeSH
• Cell Adhesion drug effects   MeSH
• Cell Differentiation drug effects   MeSH
• Cell Line MeSH
• Diamond chemistry   pharmacology   MeSH
• Physical Phenomena MeSH
• Collagen Type I chemistry   MeSH
• Silicon chemistry   MeSH
• Humans MeSH
• Nanostructures chemistry   MeSH
• Osteoblasts cytology   drug effects   immunology   MeSH
• Osteogenesis drug effects   MeSH
• Semiconductors MeSH
• Cell Proliferation drug effects   MeSH
• Cell Survival drug effects   MeSH
• Dose-Response Relationship, Drug MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Boron MeSH
• Diamond MeSH
• Collagen Type I MeSH
• Silicon MeSH

The surface of poly(L-lactide) (PLLA) films deposited on glass coverslips was modified with poly(DL-lactide) (PDLLA), or 1:4 mixtures of PDLLA and PDLLA-b-PEO block copolymers, in which either none, 5% or 20% of the copolymer molecules carried a synthetic extracellular matrix-derived ligand for integrin adhesion receptors, the GRGDSG oligopeptide, attached to the end of the PEO chain. The materials, perspective for vascular tissue engineering, were seeded with rat aortic smooth muscle cells (11,000 cells/cm(2)) and the adhesion, spreading, DNA synthesis and proliferation of these cells was followed on inert and bioactive surfaces. In 24-h-old cultures in serum-supplemented media, the number of cells adhering to the PDLLA-b-PEO copolymer was almost eight times lower than that on the control PDLLA surface. On the surfaces containing 5% and 20% GRGDSG-PEO-b-PDLLA copolymer, the number of cells increased 6- and 3-fold respectively, compared to the PDLLA-b-PEO copolymer alone. On PDLLA-b-PEO copolymer alone, the cells were typically round and non-spread, whereas on GRGDSG-modified surfaces the cell spreading areas approached those found on PDLLA, reaching values of 991 microm(2) and 611 microm(2) for 5% and 20% GRGDSG respectively, compared to 958 microm(2) for PDLLA. The cells on GRGDSG-grafted copolymers were able to form vinculin-containing focal adhesion plaques, to synthesize DNA and even proliferate in a serum-free medium, which indicates specific binding to the GRGDSG sequences through their adhesion receptors.

• MeSH
• Coated Materials, Biocompatible administration & dosage   chemistry   MeSH
• Cell Adhesion drug effects   MeSH
• Cell Culture Techniques methods   MeSH
• Rats MeSH
• Cells, Cultured MeSH
• Myocytes, Smooth Muscle cytology   drug effects   physiology   MeSH
• Oligopeptides administration & dosage   chemistry   MeSH
• Polyesters chemistry   MeSH
• Rats, Wistar MeSH
• Surface Properties MeSH
• Cell Proliferation drug effects   MeSH
• Muscle, Smooth, Vascular cytology   drug effects   physiology   MeSH
• Materials Testing MeSH
• Tissue Engineering methods   MeSH
• Cell Survival drug effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• arginyl-glycyl-aspartic acid MeSH Browser
• Coated Materials, Biocompatible MeSH
• Oligopeptides MeSH
• poly(lactide) MeSH Browser
• Polyesters MeSH