scholarly journals Chronic NOS inhibition prevents adverse lung remodeling and pulmonary arterial hypertension in caveolin-1 knockout mice

2008 ◽  
Vol 21 (3) ◽  
pp. 507-515 ◽  
Author(s):  
Carsten Wunderlich ◽  
Alexander Schmeisser ◽  
Christian Heerwagen ◽  
Bernd Ebner ◽  
Kristin Schober ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Knockout Mice ◽  
Caveolin 1 ◽  
Lung Remodeling ◽  
Pulmonary Arterial

scholarly journals Characterization of a caveolin-1 mutation associated with both pulmonary arterial hypertension and congenital generalized lipodystrophy

Traffic ◽  
2016 ◽  
Vol 17 (12) ◽  
pp. 1297-1312 ◽  
Author(s):  
Bing Han ◽  
Courtney A. Copeland ◽  
Yumeko Kawano ◽  
Erika Berman Rosenzweig ◽  
Eric D. Austin ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Caveolin 1 ◽  
Congenital Generalized Lipodystrophy ◽  
Pulmonary Arterial

Abstract 13535: The Synergistic Effects of Incretin-related Drugs for the Treatment of Pulmonary Arterial Hypertension

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Susumu Hosokawa ◽  
Go Haraguchi ◽  
Yasuhiro Maejima ◽  
Shozaburo Doi ◽  
Mitsuaki Isobe
Keyword(s):  
T Cells ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Synergistic Effects ◽  
Cell Activity ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Dipeptidyl Peptidase 4 ◽  
Caveolin 1 ◽  
Pulmonary Arterial

Introduction: A growing body of evidence suggests that inflammation plays a crucial role in the development of pulmonary arterial hypertension (PAH). Dipeptidyl peptidase-4 (DPP-4; also known as CD26), a protease which degrades incretin hormones such as glucagon-like peptide-1 (GLP-1), modulates inflammatory processes by regulating activity of T cells through co-stimulatory pathway. Hypothesis: Incretin-related drugs, including both DPP-4 inhibitors and GLP-1 receptor agonists, suppress the progression of PAH by attenuating inflammatory response of PA. Methods: Sprague Dawley rats were injected monocrotaline to induce PAH (N=80). After 14 days from PAH induction, these rats were treated with alogliptin, a DPP-4 inhibitor (M+A, N=20), liraglutide, a GLP-1 receptor agonist (M+L, N=20), both of these drugs (M+A+L, N=20), or vehicle (M, N=20). Results: A significant increase of survival was observed on days 30 after PAH induction both in the M+A and M+L compared to the M (M+A: 45%* vs. M+L: 60%* vs. M: 5%, * p <0.05). Both alogliptin and liraglutide markedly improved right ventricular pressure (M+A: 33±4.1mmHg* vs. M+L: 26±1.9mmHg* vs. M: 85.9±1.2mmHg, * p <0.05). mRNA levels of both CD28 and CD86, co-stimulators of T cells, significantly decreased and the level of caveolin-1 markedly increased in lung tissues of the M+A compared to those in the M. mRNA levels of both Tissue Factor (TF) and PAI-1 significantly decreased in lung tissues of the M+L than those in the M. Consistently, survival of rats in the M+A+L was the highest (65%) among all of the groups of PAH rats. Coimmunoprecipitation assays revealed that CD26 in T cells physically interacted with caveolin-1 in rat pulmonary vascular smooth muscle cells (rPASMCs). Immunoblot analyses showed that alogliptin suppressed caveolin-1 phosphorylation in rPASMCs. Furthermore, reporter gene assays demonstrated that alogliptin significantly inhibited the transcriptional activity of NF-κB. Conclusions: These results suggest that DPP-4 inhibition and stimulation of GLP-1 receptors synergistically mediate salutary effects on monocrotaline-induced PAH by modulating T cell activity and TF-associated signaling pathway. Thus, incretin-related drugs have a potential as a novel therapeutic tool for PAH.

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