| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Fernandez, Ruby A. Wan, Jun Song, Shanshan Smith, Kimberly A. Gu, Yali Tauseef, Mohammad Tang, Haiyang Makino, Ayako Mehta, Dolly Yuan, Jason X-J |
| Description |
Author Affiliation: Fernandez RA ( Department of Pharmacology, University of Illinois at Chicago, Chicago, Illinois); Wan J ( Department of Medicine, University of Illinois at Chicago, Chicago, Ilinois); Song S ( Department of Medicine, University of Illinois at Chicago, Chicago, Ilinois); Smith KA ( Department of Medicine, University of Illinois at Chicago, Chicago, Ilinois); Gu Y ( Division of Translational and Regenerative Medicine, Department of Medicine, The University of Arizona College of Medicine, Tucson, Arizona); Tauseef M ( Department of Pharmacology, University of Illinois at Chicago, Chicago, Illinois); Tang H ( Division of Translational and Regenerative Medicine, Department of Medicine, The University of Arizona College of Medicine, Tucson, Arizona); Makino A ( Department of Medicine, University of Illinois at Chicago, Chicago, Ilinois); Mehta D ( Department of Pharmacology, University of Illinois at Chicago, Chicago, Illinois); Yuan JX ( Department of Pharmacology, University of Illinois at Chicago, Chicago, Illinois) |
| Abstract |
Pulmonary arterial hypertension (PAH) is a progressive disease that, if left untreated, eventually leads to right heart failure and death. Elevated pulmonary arterial pressure (PAP) in patients with PAH is mainly caused by an increase in pulmonary vascular resistance (PVR). Sustained vasoconstriction and excessive pulmonary vascular remodeling are two major causes for elevated PVR in patients with PAH. Excessive pulmonary vascular remodeling is mediated by increased proliferation of pulmonary arterial smooth muscle cells (PASMC) due to PASMC dedifferentiation from a contractile or quiescent phenotype to a proliferative or synthetic phenotype. Increased cytosolic Ca(2+) concentration ([Ca(2+)]cyt) in PASMC is a key stimulus for cell proliferation and this phenotypic transition. Voltage-dependent Ca(2+) entry (VDCE) and store-operated Ca(2+) entry (SOCE) are important mechanisms for controlling [Ca(2+)]cyt. Stromal interacting molecule proteins (e.g., STIM2) and Orai2 both contribute to SOCE and we have previously shown that STIM2 and Orai2, specifically, are upregulated in PASMC from patients with idiopathic PAH and from animals with experimental pulmonary hypertension in comparison to normal controls. In this study, we show that STIM2 and Orai2 are upregulated in proliferating PASMC compared with contractile phenotype of PASMC. Additionally, a switch in Ca(2+) regulation is observed in correlation with a phenotypic transition from contractile PASMC to proliferative PASMC. PASMC in a contractile phenotype or state have increased VDCE, while in the proliferative phenotype or state PASMC have increased SOCE. The data from this study indicate that upregulation of STIM2 and Orai2 is involved in the phenotypic transition of PASMC from a contractile state to a proliferative state; the enhanced SOCE due to upregulation of STIM2 and Orai2 plays an important role in PASMC proliferation. |
| File Format |
HTM / HTML |
| ISSN |
03636143 |
| e-ISSN |
15221563 |
| DOI |
10.1152/ajpcell.00202.2014 |
| Journal |
American Journal of Physiology - Cell Physiology |
| Issue Number |
8 |
| Volume Number |
308 |
| Language |
English |
| Publisher |
American Physiological Society |
| Publisher Date |
2015-04-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Discipline Cell Biology Calcium Channels Biosynthesis Hypertension, Pulmonary Metabolism Membrane Glycoproteins Myocytes, Smooth Muscle Cytology Trpc Cation Channels Vascular Remodeling Physiology Animals Calcium Pharmacology Calcium Channel Blockers Genetics Calcium Channels, L-type Calcium Signaling Cell Dedifferentiation Cell Proliferation Cells, Cultured Mice Mice, Inbred C57bl Muscle Contraction Muscle, Smooth, Vascular Nifedipine Pulmonary Artery Rna Interference Rna, Small Interfering Rats, Sprague-dawley Transforming Growth Factor Beta Vascular Resistance Vasoconstriction Research Support, N.i.h., Extramural |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cell Biology Physiology |
