geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Dysfunctional Smad signaling contributes to abnormal smooth muscle cell proliferation in familial pulmonary arterial hypertension


, : Dysfunctional Smad signaling contributes to abnormal smooth muscle cell proliferation in familial pulmonary arterial hypertension. Circulation Research 96(10): 1053-1063

Mutations in the bone morphogenetic protein type II receptor gene (BMPR2) are the major genetic cause of familial pulmonary arterial hypertension (FPAH). Although smooth muscle cell proliferation contributes to the vascular remodeling observed in PAH, the role of BMPs in this process and the impact of BMPR2 mutation remains unclear. Studies involving normal human pulmonary artery smooth muscle cells (PASMCs) suggest site-specific responses to BMPs. Thus, BMP-4 inhibited proliferation of PASMCs isolated from proximal pulmonary arteries, but stimulated proliferation of PASMCs from peripheral arteries, and conferred protection from apoptosis. These differences were not caused by differential activation of BMP signaling pathways because exogenous BMP-4 led to phosphorylation of Smad1, p38(MAPK), and ERK1/2 in both cell types. However, the proproliferative effect of BMP-4 on peripheral PASMCs was found to be p38(MAPK)/ERK-dependent. Conversely, overexpression of dominant-negative Smad1 converted the response to BMP-4 in proximal PASMCs from inhibitory to proliferative. Furthermore, we confirmed that proximal PASMCs harboring kinase domain mutations in BMPR2 are deficient in Smad signaling and are unresponsive to the growth suppressive effect of BMP-4. Moreover, we show that the pulmonary vasculature of patients with familial and idiopathic PAH are deficient in the activated form of Smad1. We conclude that defective Smad signaling and unopposed p38(MAPK)/ERK signaling, as a consequence of mutation in BMPR2, underlie the abnormal vascular cell proliferation observed in familial PAH.

US$19.90

PMID: 15845886

DOI: 10.1161/01.RES.0000166926.54293.68


Other references

Bedell, S.E.; Agrawal, A.; Petersen, L.E., 2004: A systematic critique of diabetes on the world wide web for patients and their physicians. Purpose: The web, a widely accessed medium for patients to obtain health information, has special relevance for patients with diabetes. This paper critiques the publicly available web sites for diabetes, and it establishes criteria for excellence...

Julien Blanc; Paul R.K.edal, 2012: The Brazilian organic food sector Prospects and constraints of facilitating the inclusion of smallholders. The Brazilian organic food sector has experienced important growth during the last two decades. Brazilian smallholders, however, are facing huge challenges to enter and benefit from this growth in a sustainable way. Combining the lens of New Insti...

Som, S.; Friedman, S., 1994: Inhibition of transcription in vitro by binding of DNA (cytosine-5)-methylases to DNA templates containing cytosine analogs. DNA(cytosine-5)-methylases form tight complexes at their methylation sites when the target cytosine residue is substituted by analogs such an 5-azacytomine or 5-fluorocytosine. To test whether such complexes can block RNA transcription in vitro, t...

Rosenthal, I.M.; Linker, M.; Golomb, J., 1950: Tuberculous meningitis complicated by pyogenic meningitis caused by Streptococcus faecalis. American Review of Tuberculosis 62(4): 441-445

Chang, M.H.; Sung, J.L.; Lee, C.Y.; Chen, C.J.; Chen, J.S.; Hsu, H.Y.; Lee, P.I.; Chen, D.S., 1989: Factors affecting clearance of hepatitis B e antigen in hepatitis B surface antigen carrier children. To understand the natural history of chronic hepatitis B virus infection in children, we studied factors affecting the clearance of hepatitis B e antigen (HBeAg). One hundred sixty-nine apparently healthy children whose sera were positive for HBeA...

Nativelle, C.; Sourdaine, P.; Moslemi, S.; Seralini, G.E.; Park, C.H.; Yous, S.; Depreux, P.; Lesieur, D., 2001: New non-steroidal human aromatase inhibitors. Analytical Cellular Pathology 22(1-2): 22

Jeffery, L.S.; Connell, J.T., 1973: Control of fall panicum, johnson grass and yellow nutsedge in corn. Johnsongrass (Sorghum halepense) and yellow nutsedge (Cyperus esculentus) were well controlled by butylate at 4 lb/acre, while EPTC was also effective but required the use of a seed protectant or a 10-day interval between time of application and s...

Sim, Y.Su.; Lee, J-Hyun.; Lee, W-Yeon.; Suh, D.In.; Oh, Y-Mok.; Yoon, J-Seo.; Lee, J.Hwa.; Cho, J.Hwa.; Kwon, C.Seok.; Chang, J.Hyun., 2017: Spirometry and Bronchodilator Test. Spirometry is a physiological test for assessing the functional aspect of the lungs using an objective indicator to measure the maximum amount of air that a patient can inhale and exhale. Acceptable spirometry testing needs to be conducted three t...

Petty, R.E.; Sherry, D.D.; Johannson, J.M., 1986: IgG anti-IgA1 and anti-IgA2 antibodies: their measurement by an enzyme-linked immunosorbent assay and their relationship to disease. IgG anti-IgA antibodies were measured by an enzyme-linked immunosorbent assay using one IgA1 and one IgA2 (m1) myeloma and a pooled IgA protein preparation as antigens. Class-specific anti-IgA antibodies occurred in 0.8% of non-IgA-deficient sera...

Boogerd W.; Kroger R., 1991: Intravenous contrast in spinal computed tomography to identify epidural metastases. In 16 patients with spinal epidural metastases from various neoplasms the usefulness of intravenous (IV) contrast injection in spinal computed tomography (CT) scanning was analyzed for determining the presence and extent of the epidural lesion. In...