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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #166228
Title: RETINOIDS AND PULMONARY HYPERTENSION

Author
item PRESTON, IOANA - TUFTS-NEMC
item TANG, GUANGWEN - TUFTS-HNRCA
item TILAN, JASON - GEORGETOWN UNI MED CTR
item HILL, NICHOLAS - TUFTS-NEMC
item SUZUKI, YUICHIRO - GEORGETOWN UNI MED CTR

Submitted to: Circulation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/4/2004
Publication Date: 2/15/2005
Citation: Preston, I.R., Tang, G., Tilan, J.U., Hill, N.S., Suzuki, Y.J. 2005. Retinoids and pulmonary hypertension. Circulation. 111:782-790.

Interpretive Summary: Retinoic acid is an active form of vitamin A. It has anti-mitogenic effects on smooth muscle cells and studies on the systemic circulation suggest that it may reduce vascular thickening. Relationships between retinoic acid levels and pulmonary hypertension/pulmonary vascular remodeling, however, have not been explored. Thus, the present study examined: (i) retinoic acid levels in the plasma of patients with idiopathic pulmonary arterial hypertension, and (ii) the effects of retinoic acid on human pulmonary artery smooth muscle cell growth. We measured retinoid levels by a newly developed method in the plasma of idiopathic pulmonary arterial hypertension patients and in age and sex matched healthy controls. Patients had significantly lower levels of all-trans retinoic acid and 13-cis retinoic acid than the controls, but similar 9-cis retinoic acid and retinol levels. In cultured human pulmonary artery smooth muscle cells, all-trans retinoic acid suppressed serotonin induced cell growth. Gene array analysis showed that retinoic acid induces the expression of GADD45a, a known cell growth suppressor. Therefore, idiopathic pulmonary arterial hypertension patients have reduced retinoic acid levels that may play a role in smooth muscle cell proliferation. Our study suggest that retinoic acid treatment can elicit growth inhibitory signals in pulmonary artery smooth muscle cells in vitro,and thus reduce vascular thickening in humans.

Technical Abstract: Retinoic acid has anti-mitogenic effects on smooth muscle cells and studies on the systemic circulation suggest that it may reduce vascular thickening. Relationships between retinoids and pulmonary hypertension/pulmonary vascular remodeling, however, have not been explored. The present study examined: (i) retinoid levels in plasma of patients with idiopathic pulmonary arterial hypertension, and (ii) the effects of retinoic acid on human pulmonary artery smooth muscle cell growth. We measured retinoid levels by gas chromatograph-mass spectrometer technique in the plasma of idiopathic pulmonary arterial hypertension patients and in age and sex matched healthy controls. Patients had significantly lower levels of all-trans retinoic acid and 13-cis retinoic acid than controls, but similar 9-cis retinoic acid and retinol levels. In cultured human pulmonary artery smooth muscle cells, all-trans retinoic acid suppressed erotonininduced cell growth. These cells were found to express retinoid acid receptors RAR-alpha, beta, gama, RXR-alpha, and beta. Gene array analysis showed that retinoic acid induces the expression of GADD45a, a known cell growth suppressor. Therefore, idiopathic pulmonary arterial hypertension patients have reduced retinoic acid levels that may play a role in smooth muscle cell proliferation, and retinoic acid treatment can elicit growth inhibitory signals in pulmonary artery smooth muscle cells in vitro.