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Cellular and molecular mechanisms of pulmonary vascular remodeling
1University of Colorado Health Sciences Center, Developmental Lung Biology Laboratory, Denver 80262, USA.
Abstract:
In many organs and tissues, the cellular response to injury is associated with a reiteration of specific developmental processes. Studies have shown that, in response to injury, vascular wall cells in adult organisms express genes or gene products characteristic of earlier developmental states. Other genes, expressed preferentially in adult cells in vivo, are down-regulated following injurious stimuli. Complicating matters, however, are recent observations demonstrating that the vascular wall is comprised of phenotypically heterogeneous subpopulations of endothelial cells, smooth muscle cells, and fibroblasts. It is unclear how specific subsets of cells respond to injury and thus contribute to the vascular remodeling that characterizes chronic pulmonary hypertension. This review discusses vascular development in the lung and the cellular responses occurring in pulmonary hypertension; special attention is given to heterogeneity of responses within cell populations and reiteration of developmental processes.
Insights
Cellular responses to injury in adult tissues often mimic developmental processes. This review examines how cell heterogeneity in pulmonary hypertension contributes to vascular remodeling by reiterating developmental pathways.
Area of Science:
- Vascular biology
- Cellular biology
- Pulmonary hypertension research
Background:
- Cellular injury responses in adult tissues can recapitulate developmental processes.
- Vascular wall cells in adult organisms may revert to earlier developmental gene expression following injury.
- Adult gene expression in vascular cells can be downregulated by injurious stimuli.
Purpose of the Study:
- To review vascular development in the lung.
- To discuss cellular responses in pulmonary hypertension.
- To highlight cell population heterogeneity and developmental process reiteration in pulmonary hypertension.
Main Methods:
- Literature review of studies on vascular development and injury response.
- Analysis of gene expression changes in vascular cells following injury.
- Examination of cell subpopulation heterogeneity in the vascular wall.
Main Results:
- Cellular responses to injury often involve the reiteration of developmental processes.
- Vascular wall cells can express developmental genes or downregulate adult-specific genes after injury.
- The vascular wall contains phenotypically diverse subpopulations of endothelial cells, smooth muscle cells, and fibroblasts.
Conclusions:
- Understanding cell subpopulation responses to injury is crucial for explaining vascular remodeling in pulmonary hypertension.
- Heterogeneity in cellular responses and the reiteration of developmental processes are key factors in pulmonary hypertension pathogenesis.