Summary

Although all endothelial cells form a metabolically active, semipermeable interface between blood (or lymphatics) and tissue, considerable heterogeneity in endothelial structure and function exists even within a single vascular segment. Part of this heterogeneity is due to the environment in which a cell resides. However, endothelial cells are also imprinted during their development to impart a stable differentiated phenotype. Accordingly, endothelial cells from different sites within a blood vessel can be discriminated based upon their active gene expression profiles, even when their environments are the same. Interaction between environmental stimuli (as in blood flow patterns or transmural pressure) and the cell's origin (precapillary, capillary, postcapillary) therefore coordinately regulate site-specific endothelial cell behavior.

References

1. Majno, G., Palade, G. E., and Schoefl, G. I. (1961). Studies on inflammation. II. The site of action of histamine and serotonin along the vascular tree: A topographic study. J. Biophys. Biochem. Cytol. 11, 607-626.

2. Parker, J. C., and Yoshikawa, S. (2002). Vascular segmental permeabilities at high peak inflation pressure in isolated rat lungs. Am. J. Physiol. Lung Cell. Mol. Physiol. 283, L1203-L1209.

3. West, J. B., Mathieu-Costello, O. , Jones, J. H., Birks, E. K., Logemann, R. B., Pascoe, J. R., and Tyler, W. S. (1993). Stress failure of pulmonary capillaries in racehorses with exercise-induced pulmonary hemorrhage. J. Appl. Physiol. 75, 1097-1109.

4. Khimenko, P. L., and Taylor, A. E. (1999). Segmental microvascular permeability in ischemia-reperfusion injury in rat lung. Am. J. Physiol. 276, L958-L960.

5. Chetham, P. M., Babal, P., Bridges, J. P., Moore, T. M., and Stevens, T. (1999). Segmental regulation of pulmonary vascular permeability by store-operated Ca2+ entry. Am. J. Physiol. 276, L41-L50. This paper demonstrates that a calcium agonist (thapsigargin) increases permeability in arteries and veins, and not in capillary segments, suggesting endothelial cells exhibit site-specific responses to environmental stimuli.

6. deMello, D. E., Sawyer, D., Galvin, N., and Reid, L. M. (1997). Early fetal development of lung vasculature. Am. J. Respir. Cell. Mol. Biol. 16, 568-581. This paper demonstrates that lung macro- and microvascular segments arise from different cell origins, potentially providing the important developmental cues that impart stable cell memories.

7. King, J., Hamil, T., Creighton, J., Wu, S., Bhat, P., McDonald, F., and Stevens T. (2004). Structural and functional characteristics of lung macro- and microvascular endothelial cell phenotypes. Microvasc. Res. (in press).

8. Herman, J. G., and Baylin, S. B. (2003). Gene silencing in cancer in association with promoter hypermethylation. N. Engl. J. Med. 349, 2042-2054.

9. Habliston, D. L., Whitaker, C., Hart, M. A., Ryan, U. S., and Ryan, J. W. (1979). Isolation and culture of endothelial cells from the lungs of small animals. Am. Rev. Respir. Dis. 119, 853-868.

10. Grishko, V., Solomon, M., Wilson, G. L., LeDoux, S. P., and Gillespie, M. N. (2001). Oxygen radical-induced mitochondrial DNA damage and repair in pulmonary vascular endothelial cell phenotypes. Am. J. Physiol. Lung Cell. Mol. Physiol. 280, L1300-L1308.

11. Chi, J. T., Chang, H. Y., Haraldsen, G., Jahnsen, F. L., Troyanskaya, O. G., Chang, D. S., Wang, Z., Rockson, S. G., van de Rijn, M., Botstein, D., and Brown, P. O. (2003). Endothelial cell diversity revealed by global expression profiling. Proc. Natl. Acad. Sci. USA 100, 10623-10628. This article reports on the global mRNA expression patterns of 53 different endothelial cell populations. Hierarchical cluster analysis revealed that artery-, microvascular-, and vein-derived cells were reproducibly distinguishable based upon their selective expression patterns, indicating that a memory of their origin was retained in culture.

12. Ying, X., Minamiya, Y., Fu, C., and Bhattacharya, J. (1996). Ca2+ waves in lung capillary endothelium. Circ. Res. 79, 898-90813.

13. Parthasarathi, K., Ichimura, H., Quadri, S., Issekutz, A., and Bhat-tacharya, J. (2002). Mitochondrial reactive oxygen species regulate spatial profile of proinflammatory responses in lung venular capillaries. J. Immunol. 169, 7078-7086.

Capsule Bibliography

Dr. Al-Mehdi has held academic appointments at the University of Pennsylvania (Institute for Environmental Medicine) and, more recently, at the University of South Alabama (Assistant Professor of Pharmacology, Center for Lung Biology). His work focuses on lung vascular biology, with specific attention given to endothelial cell responses to oxygen transitions, and the role of oxygen in lung metastasis. Work in the Al-Mehdi lab is supported by the NIH.

Dr. Schaphorst has held academic appointments at Johns Hopkins University (Pulmonary and Critical Care Medicine) and, more recently, at the University of South Alabama (Associate Professor of Medicine, Center for Lung Biology). His work has addressed signal transduction networks that interplay to control endothelial cell barrier function, with emphasis on hepatocyte growth factor activation of c-Met signaling.

Dr. Stevens has held academic appointments at the University of Colorado Health Sciences Center (CVP Research Laboratory) and, more recently, at the University of South Alabama, where he is the Director of the Center for Lung Biology. His work seeks to understand the interplay between genetic and environmental factors that control endothelial cell phenotype. A major emphasis in his laboratory is to reveal the unique signal transduction pathways that control macro- and microvascular endothe-lial cell function. Work in the Stevens laboratory is supported by the NIH.

Was this article helpful?

0 0
Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

Get My Free Ebook


Post a comment