Biomedical subjects

Mercedes Balcells

Publications and source records attributed to Mercedes Balcells.

5 recordsLinked to original sources

PubMed2007

Vascular bed origin dictates flow pattern regulation of endothelial adhesion molecule expression.

Endothelial cell phenotypes markedly differ, depending upon function and vascular bed of origin. Differences might account for specific susceptibility to pathological conditions. As leukocyte adhesion to activated endothelium is the initiating event in a range of diseases, we compared the influence of vascular bed-specific flow patterns on adhesion molecule expression in human saphenous vein (HSVEC) and coronary artery endothelial cells (HCAEC). In vitro, immune cell attachment was increased 1.6-fold when tumor necrosis factor (TNF)-alpha-stimulated HSVEC were exposed to coronary artery flow in place of physiological venous flow and 1.9-fold higher compared with attachment to cytokine-stimulated HCAEC exposed to coronary artery flow. This was associated with increased concentrations of soluble E-selectin, VCAM-1, and ICAM-1 in supernatants of HSVEC exposed to coronary artery flow compared with HCAEC exposed to the same flow pattern. Venous and coronary artery flow both increased TNF-alpha-induced E-selectin and ICAM-1 expression on HSVEC, but only coronary artery flow increased VCAM-1 expression. In marked contrast to HSVEC, venous and coronary artery flow attenuated TNF-alpha-induced E-selectin and VCAM-1 expression on HCAEC, whereas coronary artery flow further induced ICAM-1 on cytokine-stimulated HCAEC. With the exception of cytokine-induced ICAM-1, adhesion molecule expression on HSVEC exposed to coronary artery flow exceeded expression on HCAEC. Thus ICAM-1 expression involves complex flow-dependent and -independent pathways with marked dissimilarities between the two endothelial cell types studied. Interestingly, Kruppel-like factor (KLF) 4 overexpression in HCAEC and HSVEC significantly reduced TNF-alpha-induced E-selectin and VCAM-1 expression in static conditions, while ICAM-1 expression remained constant. Furthermore, both flow patterns induced KLF2 and KLF4 expression in HCAEC and HSVEC. Venous and coronary artery flow differentially influence endothelial adhesion molecule and transcription factor expression, depending on the vascular bed of origin. Differences in adhesion molecule expression and subsequent immune cell adhesion between HSVEC and HCAEC may contribute to different susceptibility to pathological conditions.

Blood Flow Velocity↗

PubMed2005

Proangiogenic stimulation of bone marrow endothelium engages mTOR and is inhibited by simultaneous blockade of mTOR and NF-kappaB.

Most bone marrow (BM) malignancies develop in association with an angiogenic phenotype and increased numbers of endothelial cells. The molecular mechanisms involved in the modulation and recruitment of BM endothelium are largely unknown and may provide novel therapeutic targets for neoplastic diseases. We observed that angiogenic stimulation of BM endothelial cells activates mTOR and engages its downstream pathways 4E-BP1 and S6K1, which are inhibited by the mTOR-specific blockers rapamycin and CCI-779. Both mTOR blockers significantly inhibit growth factor- and leukemia-induced proliferation of BM endothelium by inducing G0/G1 cell-cycle arrest. This effect is associated with down-regulation of cyclin D1 and cdk2 phosphorylation, and up-regulation of the cdk inhibitors p27(kip1) and p21(cip1). Under conditions that reproduce the biomechanical fluidic environment of the BM, CCI-779 is equally effective in inhibiting BM endothelial-cell proliferation. Finally, simultaneous blockade of mTOR and NF-kappaB pathways synergize to significantly inhibit or abrogate the proliferative responses of BM endothelial cells to mitogenic stimuli. This study identifies mTOR as an important pathway for the proangiogenic stimulation of BM endothelium. Modulation of this pathway may serve as a valid therapeutic intervention in BM malignancies evolving in association with an angiogenic phenotype.

Adult↗

PubMed2005

Cells in fluidic environments are sensitive to flow frequency.

Virtually all cells accommodate to their mechanical environment. In particular, cells subject to flow respond to rapid changes in fluid shear stress (SS), cyclic stretch (CS), and pressure. Recent studies have focused on the effect of pulsatility on cellular behavior. Since cells of many different tissue beds are constantly exposed to fluid flows over a narrow range of frequencies, we hypothesized that an intrinsic flow frequency that is optimal for determining cell phenotype exists. We report here that cells from various tissue beds (bovine aortic endothelial cells (BAEC), rat small intestine epithelial cells (RSIEC), and rat lung epithelial cells (RLEC)) proliferate maximally when cultured in a perfusion bioreactor under pulsatile conditions at a specific frequency, independent of the applied SS. Vascular endothelial and pulmonary epithelial cell proliferation peaked under 1 Hz pulsatile flow. In contrast, proliferation of gastrointestinal cells, which in their physiological context are subject to no flow or higher wavelength signal, was maximum at 0.125 Hz or under no flow. Moreover, exposure of BAEC to pulsatile flow of varying frequency influenced their nitric oxide synthase activity and prostacyclin production, which reached maximum values at 1 Hz. Notably, the "optimal" frequencies for the cell types examined correspond to the physiologic operating range of the organs from where they were initially derived. These findings suggest that frequency, independent of shear, is an essential determinant of cell response in pulsatile environments.

Animals↗

PubMed2003

Reactive polymer coatings: a first step toward surface engineering of microfluidic devices.

We report fabrication, characterization, and use of microfluidic analysis devices containing surface-immobilized cell-capturing molecules. Amino-terminated biotin ligands are immobilized onto the luminal surface of a microdevice and effectively support self-assembly of proteins, antibodies, and mammalian cells. For this purpose, chemical vapor deposition (CVD) polymerization is used to functionalize PDMS-made microfluidic devices with poly[para-xylylene carboxylic acid pentafluorophenolester-co-para-xylylene]. The resulting reactive coating shows excellent adhesion when deposited in thin films (approximately 100 nm, and the distribution of the pentafluorophenol ester groups is reasonably uniform within the microchannel inner surface, as examined by fluorescence microscopy. The utility of these devices for cell-based bioassays is demonstrated by monitoring the concentration-dependent effect of the disintegrin echistatin on cell adhesion. The described assay format could be relevant to clinical research in various fields, including angiogenesis research.

Animals↗

PubMed2002

Effect of pre-adsorbed proteins on attachment, proliferation, and function of endothelial cells.

As certain proteins control cell adhesion, it has been hoped that cell transplantation and tissue engineering could be augmented by pre-adsorption of specific proteins to biological or synthetic surfaces. The questions that remain, however, are whether such proteins can affect cell production as well as adhesion, and if so, whether in a protein-specific manner. We examined the adhesion and the biochemical secretion of bovine aortic endothelial cells (BAEC) on tissue culture polystyrene (TCPS) discs coated with fibronectin (Fn), laminin (Ln), or gelatin. The three coating proteins nonspecifically promote sub-confluent and post-confluent endothelial cell production of total protein up to 2.5-fold of the reference value. Total soluble glycosaminoglycan (GAG) production slightly increased with the different coatings only at low cell density. In contrast, Ln and Fn, not gelatin, drastically enhanced post-confluent BAEC production of prostaglandin (PGI2). However, antibody-blockage of the alpha5 integrin, constituent of the Fn receptor in BAEC, appeared to inhibit the upregulation of PGI2 production observed on Fn-coated surfaces. The results indicate that the cell adhesion mediators used as coating agents dictate cell biological production as well as adhesion and proliferation.

Adsorption↗