Biomedical subjects

Eric J Van Gieson

Publications and source records attributed to Eric J Van Gieson.

4 recordsLinked to original sources

PubMed2004

Multicellular simulation predicts microvascular patterning and in silico tissue assembly.

Remodeling of microvascular networks in mammals is critical for physiological adaptations and therapeutic revascularization. Cellular behaviors such as proliferation, differentiation, and migration are coordinated in these remodeling events via combinations of biochemical and biomechanical signals. We developed a cellular automata (CA) computational simulation that integrates epigenetic stimuli, molecular signals, and cellular behaviors to predict microvascular network patterning events. Over 50 rules obtained from published experimental data govern independent behaviors (including proliferation, differentiation, and migration) of thousands of interacting cells and diffusible growth factors in their tissue environment. From initial network patterns of in vivo blood vessel networks, the model predicts emergent patterning responses to two stimuli: 1) network-wide changes in hemodynamic mechanical stresses, and 2) exogenous focal delivery of an angiogenic growth factor. The CA model predicts comparable increases in vascular density (370+/-29 mm/mm3) 14 days after treatment with exogenous growth factor to that in vivo (480+/-41 mm/mm3) and approximately a twofold increase in contractile vessel lengths 5-10 days after 10% increase in circumferential wall strain, consistent with in vivo results. The CA simulation was thus able to identify a functional patterning module capable of quantitatively predicting vessel network remodeling in response to two important epigenetic stimuli.

Cell Differentiation↗

PubMed2004

Cell proliferation in mesenteric microvascular network remodeling in response to elevated hemodynamic stress.

The objective of this study was to quantify the proliferation of existing vascular and perivascular cells during a specific form of microvascular remodeling characterized by increased coverage by smooth muscle cells (SMCs), in response to increased mechanical stress. Coordinated ligations of artery/vein pairs in the rat mesentery resulted in hemodynamic stress elevations within the targeted microvascular network. BRDU incorporation per unit length of smooth muscle (SM) alpha-actin positive vessel was evaluated following ligation at 2, 5, and 10 days. At 2 days, BRDU incorporation was significantly increased for both sham and ligated treatments, but the ligated response was not elevated over the sham response. After 5 days, proliferation for both groups returned to unstimulated levels. The results indicate that moderate elevations in hemodynamic stress do not cause perivascular cell proliferation along rat mesenteric microvessels, therefore, the increased coverage of differentiated SMCs along the same microvessels does not involve proliferation of vascular or perivascular cells.

Actins↗

PubMed2003

Enhanced smooth muscle cell coverage of microvessels exposed to increased hemodynamic stresses in vivo.

During vascular remodeling in adult organisms, new capillary growth is often coupled with the adaptation of arterioles and venules, a process that requires the recruitment and differentiation of precursor cells into smooth muscle. We studied the in vivo adaptation of microvessels in the presence of elevated pressure and circumferential wall stress using a ligation strategy for mesenteric microvascular networks. Acute pressure increases of 42.6+/-18% and 17.1+/-2.3% were respectively elicited in the 25- to 30-microm-diameter venules and arterioles supplying the networks. Wall shear rates were not significantly changed; however, diameters were increased in >10-microm-diameter venules and >20-microm-diameter arterioles. Smooth muscle cell contractile phenotype was determined in all microvessels by observing the expression of smooth muscle myosin heavy chain (SM-MHC; a marker of fully differentiated smooth muscle) and smooth muscle alpha-actin (a marker for all smooth muscle, including immature smooth muscle of fibroblast/pericyte lineage). The ratio of SM-MHC positive vessel length to smooth muscle alpha-actin-positive vessel length increased >2-fold after 5 and 10 days of the ligation treatment. Smooth muscle proliferation was studied by bromodeoxyuridine incorporation, and the increase in SM-MHC-labeled microvessel length density was accompanied by no measurable change in proliferation of SM-MHC-labeled cells 5 and 10 days after ligation. These results indicate that after a period of 5 or 10 days, mesenteric microvessels <40 microm in diameter exposed to elevated pressure and wall strain exhibit an enhanced coverage of mature, fully differentiated smooth muscle cells.

Actins↗

PubMed2002

Hemodynamic stresses and structural remodeling of anastomosing arteriolar networks: design principles of collateral arterioles.

OBJECTIVE: To investigate the potential influence of hemodynamic stresses on the development of the arcade arteriole (AA) network during normal maturation. METHODS: AA network data were collected from ink-filled Wistar-Kyoto rat gracilis muscles and used to construct hemodynamic computational models of the AA network at 7 (WKY(7)) and 13 (WKY(13)) weeks of age. RESULTS: Mean coefficients of variation for pressure, circumferential wall stress, and wall shear stress were 0.13, 0.12, and 0.48, respectively. Wall shear rate variability across bifurcations generated deviations in mean energy cost that were 9-30% above theoretical minimum, with many bifurcations exhibiting substantially higher energy costs. With the exception of the lowest pressure AA segments, the monotonic relationship between wall shear stress and pressure in the AAs was nearly identical from 7 to 13 weeks of age. CONCLUSIONS: Low coefficients of variation for computed AA pressures indicate that an even pressure head is maintained over the muscle during remodeling of the AA network. The anastomotic structure of the network creates high shear rate variability that, in turn, creates high-energy costs in some regions of the network. The results are consistent with the hypothesis that, during development, the maintenance of mean circumferential wall stress and the pressure-shear stress relationship are operative design principles for collateral arteriole development.

Animals↗