Regulation of pulmonary vascular wall cell growth: Developmental and site- specific heterogeneity

K. R. Stenmark, E. C. Dempsey, D. B. Badesch, M. Frid, R. P. Mecham, W. C. Parks

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

A common observation in many models of pulmonary hypertension is that of a phenotypically altered smooth muscle cell (SMC) that first appears to escape from its normal tightly controlled state of quiescence and then produces not only more but different connective tissue components than do cells in the normal vessel. The result is an increase in wall mass and a vessel with altered mechanical and functional properties. Evidence is accumulating to suggest that SMC and fibroblasts in the vascular wall can respond directly to changes in local environmental conditions with increased production of growth and differentiation factors, (e.g. platelet derived growth factor) capable of acting in autocrine or paracrine fashions on vascular wall cells. In models of pulmonary hypertension, increased production of transforming growth factor beta and insulin-like growth factor-I (IGF-I) have been correlated in a temporal fashion with the changes in cell proliferation and matrix protein production by SMC. Further, an as yet unidentified factor(s), smooth muscle derived elastogenic factor, has been shown to be produced by phenotypically altered SMC from the hypertensive vessel wall and is capable of upregulating elastin and collagen synthesis in vascular wall cells. Recent observations demonstrate that SMC in the pulmonary artery are a diverse population of cells capable of expressing multiple phenotype. This variety raises the possibility that some smooth muscle cells might have a signalling function while others respond to the signals they generate. In this case, it will not only be important to know which cells are secreting which cytokines, but also which cells are expressing the receptors that will recognize the cytokines. Understanding how these phenotypes are modulated by environmental and development stimuli will be the key to understanding vascular remodelling in disease.

Original languageEnglish
Pages (from-to)629-637
Number of pages9
JournalEuropean Respiratory Review
Volume3
Issue number16
StatePublished - 1993
Externally publishedYes

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