Inhibition of pulmonary artery smooth muscle cell growth by hypoxanthine, xanthine, and uric acid.

P. M. Hassoun, A. L. Shedd, J. J. Lanzillo, V. Thappa, M. J. Landman, B. L. Fanburg

Research output: Contribution to journalArticlepeer-review

Abstract

We have previously reported that medium conditioned by hypoxic pulmonary artery endothelial cells (ECCM) contains a factor of small molecular weight that inhibits the growth of pulmonary artery smooth muscle cells (SMC). We postulated that this factor might be a breakdown product of ATP and, therefore, measured the levels of hypoxanthine/xanthine (HX/X) and uric acid (UA) in ECCM and cell lysates from endothelial cells (EC) exposed to hypoxia and normoxia. Although hypoxic and normoxic cell lysates contained no UA and an equal amount of HX/X (2.9 +/- 0.3 and 2.9 +/- 0.5 microM, respectively), there was a 5-fold increase in the amount of HX/X present in hypoxic compared with normoxic ECCM (3.4 +/- 0.3 versus 0.6 +/- 0.4 microM, respectively; P less than 0.001) but no difference in UA levels (5 +/- 2 versus 5 +/- 1 microM, respectively). In separate experiments, we examined the effects of exogenous HX, X, and UA (doses ranging from 0.1 to 100 microM) on the proliferation of pulmonary and aortic SMC and pulmonary artery EC. Our results indicate that HX, X, and UA inhibit the proliferation of SMC in a dose-dependent manner without causing injury to the cells. The proliferation of EC, on the other hand, was not affected by UA and was significantly inhibited by HX and X only at doses of 100 microM. In conclusion, we have found that significant amounts of HX/X accumulate in hypoxic ECCM and that HX, X, and UA inhibit the proliferation of SMC. The relevance of these findings to conditions where hypoxia prevails is discussed.

Original languageEnglish (US)
Pages (from-to)617-624
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume6
Issue number6
DOIs
StatePublished - Jun 1992
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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