scholarly journals Regulation of Pulmonary Vascular Smooth Muscle Contractility in Pulmonary Arterial Hypertension: Implications for Therapy

2017 ◽  
Vol 8 ◽  
Author(s):  
Melissa A. Lyle ◽  
Jonathan P. Davis ◽  
Frank V. Brozovich
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Arterial Hypertension ◽  
Vascular Smooth Muscle ◽  
Arterial Hypertension ◽  
Muscle Contractility ◽  
Smooth Muscle Contractility ◽  
Pulmonary Arterial

scholarly journals Profiling the Role of Mammalian Target of Rapamycin in the Vascular Smooth Muscle Metabolome in Pulmonary Arterial Hypertension

2015 ◽  
Vol 5 (4) ◽  
pp. 667-680 ◽  
Author(s):  
Tatiana V. Kudryashova ◽  
Dmitry A. Goncharov ◽  
Andressa Pena ◽  
Kaori Ihida-Stansbury ◽  
Horace DeLisser ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Arterial Hypertension ◽  
Vascular Smooth Muscle ◽  
Arterial Hypertension ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Pulmonary Arterial

scholarly journals Inhibitory Antibodies against Activin A and TGF-β Reduce Self-Supported, but Not Soluble Factors-Induced Growth of Human Pulmonary Arterial Vascular Smooth Muscle Cells in Pulmonary Arterial Hypertension

2018 ◽  
Vol 19 (10) ◽  
pp. 2957 ◽  
Author(s):  
Tatiana Kudryashova ◽  
Yuanjun Shen ◽  
Andressa Pena ◽  
Emily Cronin ◽  
Evelyn Okorie ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Arterial Hypertension ◽  
Vascular Smooth Muscle ◽  
Arterial Hypertension ◽  
Smooth Muscle Cells ◽  
P38 Mapk ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Activin A ◽  
Pulmonary Arterial

Increased growth and proliferation of distal pulmonary artery vascular smooth muscle cells (PAVSMC) is an important pathological component of pulmonary arterial hypertension (PAH). Transforming Growth Factor-β (TGF-β) superfamily plays a critical role in PAH, but relative impacts of self-secreted Activin A, Gremlin1, and TGF-β on PAH PAVSMC growth and proliferation are not studied. Here we report that hyper-proliferative human PAH PAVSMC have elevated secretion of TGF-β1 and, to a lesser extent, Activin A, but not Gremlin 1, and significantly reduced Ser465/467-Smad2 and Ser423/425-Smad3 phosphorylation compared to controls. Media, conditioned by PAH PAVSMC, markedly increased Ser465/467-Smad2, Ser423/425-Smad3, and Ser463/465-Smad1/5 phosphorylation, up-regulated Akt, ERK1/2, and p38 MAPK, and induced significant proliferation of non-diseased PAVSMC. Inhibitory anti-Activin A antibody reduced PAH PAVSMC growth without affecting canonical (Smads) or non-canonical (Akt, ERK1/2, p38 MAPK) effectors. Inhibitory anti-TGF-β antibody significantly reduced P-Smad3, P-ERK1/2 and proliferation of PAH PAVSMC, while anti-Gremlin 1 had no anti-proliferative effect. PDGF-BB diminished inhibitory effects of anti-Activin A and anti-TGF-β antibodies. None of the antibodies affected growth and proliferation of non-diseased PAVSMC induced by PAH PAVSMC-secreted factors. Together, these data demonstrate that human PAH PAVSMC have secretory, proliferative phenotype that could be targeted by anti-Activin A and anti-TGF-β antibodies; potential cross-talk with PDGF-BB should be considered while developing therapeutic interventions.

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