G protein-coupled receptor expression and function in pulmonary artery smooth muscle cells

new targets in pulmonary arterial hypertension

Daniel McDonald, Nakon Aroonsakool, Ohmin Kwon, Paul Insel, Fiona Murray

Research output: Contribution to journalAbstract

Abstract

Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, in part due to increased proliferation of pulmonary artery smooth muscle cells (PASMC). Since 3’5’-cyclic adenosine monophosphate (cAMP) decreases proliferation of PASMC, G protein-coupled receptors (GPCRs) that couple to Gαs or Gαi are attractive targets for the treatment of PAH. We used a real-time PCR GPCR array to identify and quantify the GPCRs expressed by PASMC isolated from normal subjects and from patients with PAH. We found that human PASMC express >135 GPCRs, at least 60 of which regulate cAMP formation. GPCR expression correlates with function: for Gαs-coupled GPCRs with formation of cAMP and inhibition of cell proliferation, thus documenting that the GPCR array identifies physiologically relevant GPCRs. PAH-PASMC (both from idiopathic and secondary PAH patients) have an increase (>2-fold) in the expression of 41 GPCRs compared to control-PASMC, including multiple GPCRs that link to Gαs or Gαi. In addition, PAH-PASMC have a higher expression of GPCRs that preferentially couple to Gαq/11 or to Gα12/13. Taken together these data provide evidence that a GPCRomic approach can identify GPCRs that may contribute to the physiology of PASMC and that may be new druggable targets for PAH, a disease for which no currently optimal therapies exist.
Original languageEnglish
Article number1090.3
Number of pages1
JournalThe FASEB Journal
Volume28
Issue numberSuppl 1
Publication statusPublished - Apr 2014

Cite this

G protein-coupled receptor expression and function in pulmonary artery smooth muscle cells : new targets in pulmonary arterial hypertension. / McDonald, Daniel; Aroonsakool, Nakon; Kwon, Ohmin; Insel, Paul; Murray, Fiona.

In: The FASEB Journal, Vol. 28, No. Suppl 1, 1090.3, 04.2014.

Research output: Contribution to journalAbstract

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title = "G protein-coupled receptor expression and function in pulmonary artery smooth muscle cells: new targets in pulmonary arterial hypertension",
abstract = "Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, in part due to increased proliferation of pulmonary artery smooth muscle cells (PASMC). Since 3’5’-cyclic adenosine monophosphate (cAMP) decreases proliferation of PASMC, G protein-coupled receptors (GPCRs) that couple to Gαs or Gαi are attractive targets for the treatment of PAH. We used a real-time PCR GPCR array to identify and quantify the GPCRs expressed by PASMC isolated from normal subjects and from patients with PAH. We found that human PASMC express >135 GPCRs, at least 60 of which regulate cAMP formation. GPCR expression correlates with function: for Gαs-coupled GPCRs with formation of cAMP and inhibition of cell proliferation, thus documenting that the GPCR array identifies physiologically relevant GPCRs. PAH-PASMC (both from idiopathic and secondary PAH patients) have an increase (>2-fold) in the expression of 41 GPCRs compared to control-PASMC, including multiple GPCRs that link to Gαs or Gαi. In addition, PAH-PASMC have a higher expression of GPCRs that preferentially couple to Gαq/11 or to Gα12/13. Taken together these data provide evidence that a GPCRomic approach can identify GPCRs that may contribute to the physiology of PASMC and that may be new druggable targets for PAH, a disease for which no currently optimal therapies exist.",
author = "Daniel McDonald and Nakon Aroonsakool and Ohmin Kwon and Paul Insel and Fiona Murray",
note = "Grant Funding Source: NIH",
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T1 - G protein-coupled receptor expression and function in pulmonary artery smooth muscle cells

T2 - new targets in pulmonary arterial hypertension

AU - McDonald, Daniel

AU - Aroonsakool, Nakon

AU - Kwon, Ohmin

AU - Insel, Paul

AU - Murray, Fiona

N1 - Grant Funding Source: NIH

PY - 2014/4

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N2 - Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, in part due to increased proliferation of pulmonary artery smooth muscle cells (PASMC). Since 3’5’-cyclic adenosine monophosphate (cAMP) decreases proliferation of PASMC, G protein-coupled receptors (GPCRs) that couple to Gαs or Gαi are attractive targets for the treatment of PAH. We used a real-time PCR GPCR array to identify and quantify the GPCRs expressed by PASMC isolated from normal subjects and from patients with PAH. We found that human PASMC express >135 GPCRs, at least 60 of which regulate cAMP formation. GPCR expression correlates with function: for Gαs-coupled GPCRs with formation of cAMP and inhibition of cell proliferation, thus documenting that the GPCR array identifies physiologically relevant GPCRs. PAH-PASMC (both from idiopathic and secondary PAH patients) have an increase (>2-fold) in the expression of 41 GPCRs compared to control-PASMC, including multiple GPCRs that link to Gαs or Gαi. In addition, PAH-PASMC have a higher expression of GPCRs that preferentially couple to Gαq/11 or to Gα12/13. Taken together these data provide evidence that a GPCRomic approach can identify GPCRs that may contribute to the physiology of PASMC and that may be new druggable targets for PAH, a disease for which no currently optimal therapies exist.

AB - Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, in part due to increased proliferation of pulmonary artery smooth muscle cells (PASMC). Since 3’5’-cyclic adenosine monophosphate (cAMP) decreases proliferation of PASMC, G protein-coupled receptors (GPCRs) that couple to Gαs or Gαi are attractive targets for the treatment of PAH. We used a real-time PCR GPCR array to identify and quantify the GPCRs expressed by PASMC isolated from normal subjects and from patients with PAH. We found that human PASMC express >135 GPCRs, at least 60 of which regulate cAMP formation. GPCR expression correlates with function: for Gαs-coupled GPCRs with formation of cAMP and inhibition of cell proliferation, thus documenting that the GPCR array identifies physiologically relevant GPCRs. PAH-PASMC (both from idiopathic and secondary PAH patients) have an increase (>2-fold) in the expression of 41 GPCRs compared to control-PASMC, including multiple GPCRs that link to Gαs or Gαi. In addition, PAH-PASMC have a higher expression of GPCRs that preferentially couple to Gαq/11 or to Gα12/13. Taken together these data provide evidence that a GPCRomic approach can identify GPCRs that may contribute to the physiology of PASMC and that may be new druggable targets for PAH, a disease for which no currently optimal therapies exist.

M3 - Abstract

VL - 28

JO - The FASEB Journal

JF - The FASEB Journal

SN - 0892-6638

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