Pulmonary arterial hypertension is a progressive disease characterized by lung endothelial cell dysfunction and vascular remodeling. Normally, the endothelium forms an integral cellular barrier to regulate vascular homeostasis. During embryogenesis endothelial cells exhibit substantial plasticity that contribute to cardiac development by undergoing endothelial-to-mesenchymal transition (EndoMT). Here, we determined the presence of EndoMT in the pulmonary vasculature in vivo and the functional effects of pulmonary artery endothelial cells (PAECs) that undergo EndoMT in vitro. Histologic assessment of pulmonary vessels from patients with systemic sclerosis-associated pulmonary arterial hypertension and the hypoxia/SU5416 mouse model identified the presence von Willebrand factor/α-smooth muscle actin-positive endothelial cells in up to 5% of pulmonary vessels. Induced EndoMT in PAECs by inflammatory cytokines IL-1β, tumor necrosis factor α, and transforming growth factor β led to actin cytoskeleton reorganization and the development of a mesenchymal morphology. Induced EndoMT cells exhibited up-regulation of mesenchymal markers, including collagen type I and α-smooth muscle actin, and a reduction in endothelial cell and junctional proteins, including von Willebrand factor, CD31, occludin, and vascular endothelial-cadherin. Consistently, induced EndoMT monolayers failed to form viable biological barriers and induced enhanced leak in co-culture with PAECs. Furthermore, induced EndoMT cells secreted significantly elevated proinflammatory cytokines, including IL-6, IL-8, and tumor necrosis factor α, and supported higher immune transendothelial migration compared with PAECs. These findings suggest that EndoMT may contribute to the development of pulmonary arterial hypertension.
Pharmacology, Toxicology and Pharmaceutical Science
8
4%
Engineering
6
3%
Other
19
8%
Unknown
66
29%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 July 2015.
All research outputs
#21,400,120
of 34,360,257 outputs
Outputs from American Journal of Pathology
#7,300
of 9,009 outputs
Outputs of similar age
#171,777
of 306,960 outputs
Outputs of similar age from American Journal of Pathology
#39
of 74 outputs
Altmetric has tracked 34,360,257 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 9,009 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.1. This one is in the 18th percentile – i.e., 18% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 306,960 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 43rd percentile – i.e., 43% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 74 others from the same source and published within six weeks on either side of this one. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.
