scholarly journals The Role of Peroxisome Proliferator-Activated Receptors in Pulmonary Vascular Disease

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-10 ◽  
Author(s):  
Rachel E. Nisbet ◽  
Roy L. Sutliff ◽  
C. Michael Hart
Keyword(s):  
Pulmonary Hypertension ◽  
Vascular Disease ◽  
Vascular Dysfunction ◽  
Treatment Strategies ◽  
Underlying Disease ◽  
Nuclear Hormone Receptor ◽  
Pulmonary Vascular Disease ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Function

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily that regulate diverse physiological processes ranging from lipogenesis to inflammation. Recent evidence has established potential roles of PPARs in both systemic and pulmonary vascular disease and function. Existing treatment strategies for pulmonary hypertension, the most common manifestation of pulmonary vascular disease, are limited by an incomplete understanding of the underlying disease pathogenesis and lack of efficacy indicating an urgent need for new approaches to treat this disorder. Derangements in pulmonary endothelial-derived mediators and endothelial dysfunction have been shown to play a pivotal role in pulmonary hypertension pathogenesis. Therefore, the following review will focus on selected mediators implicated in pulmonary vascular dysfunction and evidence that PPARs, in particular PPARγ, participate in their regulation and may provide a potential novel therapeutic target for the treatment of pulmonary hypertension.

scholarly journals The Role of PPARγ in Pulmonary Vascular Disease

2008 ◽  
Vol 56 (2) ◽  
pp. 518-521 ◽  
Author(s):  
C. Michael Hart
Keyword(s):  
Pulmonary Hypertension ◽  
Experimental Models ◽  
Nuclear Hormone Receptor ◽  
Vascular Lesions ◽  
Current Evidence ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

The peroxisome proliferator-activated receptor (PPAR) γ is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Thiazolidinediones, pharmacological ligands for PPARγ, are currently used in the management of type 2 diabetes. Peroxisome proliferator-activated receptor γ is expressed in the lung and pulmonary vasculature, and its expression is reduced in the vascular lesions of patients with pulmonary hypertension. Furthermore, thiazolidinedione PPARγ ligands reduced pulmonary hypertension and vascular remodeling in several experimental models of pulmonary hypertension. This report reviews current evidence that PPARγ may represent a novel therapeutic target in pulmonary hypertension and examines studies that have begun to elucidate mechanisms that underlie these potential therapeutic effects.

Pulmonary Vascular Disease in Secundum Atrial Septal Defect with Pulmonary Hypertension

CHEST Journal ◽  
1986 ◽  
Vol 89 (5) ◽  
pp. 694-698 ◽  
Author(s):  
Shigeo Yamaki ◽  
Togo Horiuchi ◽  
Makoto Miura ◽  
Yasuyuki Suzuki ◽  
Eiji Ishizawa ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Atrial Septal Defect ◽  
Vascular Disease ◽  
Septal Defect ◽  
Pulmonary Vascular Disease ◽  
Secundum Atrial Septal Defect

scholarly journals Peroxisome Proliferator-Activated Receptors (PPARs) Activation as Therapeutic Targets in Skin Inflammation

2020 ◽  
Vol 4 (2) ◽  
pp. 9
Author(s):  
Akihiro Aioi
Keyword(s):  
Skin Diseases ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
Cell Types ◽  
Immune Dysregulation ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Barrier Dysfunction ◽  
Cytokine Network ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) are fatty acid activated transcription factors that belong to the nuclear hormone receptor family. They are initially known as transcriptional regulators of lipid and glucose metabolism, although further evidence has also been accumulated for other functions. Due to the nature of all PPAR isotypes which are expressed and exert effects by regulating the functions of cell types residing and infiltrating in the skin, PPARs represent a major research target for the understanding and treatment of many skin diseases. Atopic dermatitis (AD) is a chronic and relapsing disease characterized by skin barrier dysfunction and immune dysregulation. Skin barrier disturbance is one of the exacerbation factors of AD, due to facile penetration of molecules such as antigens. From the aspect of immune dysregulation, innate and acquired immunity including cell proliferation, cell differentiation, and cytokine network are involved in the pathogenesis. In this review, the role of PPAR in AD and the possibility of its agonist for the treatment of AD are discussed.

Abstract 15542: Late Pulmonary Hypertension in Surgically Palliated D-transposition of the Great Arteries: A 55-year Review

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Blair Suter ◽  
Dylan Hall ◽  
Eric S Ebenroth ◽  
Larry W Markham ◽  
Michael Johansen
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Late Onset ◽  
Systolic Dysfunction ◽  
Left Lung ◽  
Treatment Strategies ◽  
Lung Hypoplasia ◽  
Pulmonary Vascular Disease ◽  
Complete Evaluation ◽  
Lost To Follow Up

Introduction: Pulmonary hypertension (PH) has been described following surgical palliation for transposition of the great arteries (D-TGA). While early pulmonary vascular disease is associated with late repair, the increasing prevalence of late PH has been observed following the intra-atrial baffle procedure (ABP), Mustard/Senning. A previous study from our institution identified patients with precapillary PH. More recent studies have described predominately postcapillary PH, suggesting multiple, differing mechanisms for this complication. Hypothesis: While heart failure is a common complication following ABP and is associated with postcapillary PH, we hypothesize that precapillary PH can be identified in a subset of patients. Methods: A retrospective descriptive study was performed at a single institution. Using 6 th World Symposium on Pulmonary Hypertension definitions. PH was defined as a mean pulmonary artery pressure >20mmHg. Etiology of PH was defined as precapillary (≥3 Wood units) versus postcapillary (pulmonary artery wedge pressure >15 mmHg). Results: We reviewed 157 D-TGA patients following ABP, finding 33 patients with PH. Mean age at last evaluation was 36.6 (14-54) years. Current condition: 22 alive, 7 dead, and 4 lost to follow-up. Etiology of PH: 10 precapillary, 8 postcapillary, 8 mixed, 2 borderline PH, and 2 did not undergo catherization. Additionally, 2 patients had pulmonary venous baffle obstruction and 1 had left lung hypoplasia. Of patients with recent imaging, 21 of 25 had systemic RV systolic dysfunction on echocardiogram or MRI. Conclusions: Late-onset PH in D-TGA following ABP is a significant long-term complication and warrants vigilant surveillance. This highlights the limitations of imaging and need for catheterization for complete evaluation. In this study, we observed precapillary PH in a majority of patients with PH, which differs from some previous studies. Identifying the etiology of PH could drastically alter treatment strategies and has implications for transplant consideration. Further studies are needed to identify the clinical attributes that contribute to this process.

scholarly journals Lower DLco% identifies exercise pulmonary hypertension in patients with parenchymal lung disease referred for dyspnea

2020 ◽  
Vol 10 (1) ◽  
pp. 204589401989191 ◽  
Author(s):  
Richard H. Zou ◽  
William D. Wallace ◽  
S. Mehdi Nouraie ◽  
Stephen Y. Chan ◽  
Michael G. Risbano
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Disease ◽  
Vascular Disease ◽  
Pulmonary Function Tests ◽  
Pulmonary Vascular Disease ◽  
Chronic Obstructive ◽  
Exertional Dyspnea ◽  
Pulmonary Arterial ◽  
Parenchymal Lung Disease ◽  
Parenchymal Lung

Exercise pulmonary hypertension is an underappreciated form of physical limitation related to early pulmonary vascular disease. A low diffusing capacity of lungs for carbon monoxide (DLco) can be seen in patients with resting pulmonary hypertension as well as parenchymal lung disease. It remains unclear whether low DLco% identifies early pulmonary vascular disease. We hypothesize that a reduced DLco% differentiates the presence of exercise pulmonary hypertension in patients with parenchymal lung disease. Fifty-six patients referred for unexplained exertional dyspnea with pulmonary function tests within six months of hemodynamic testing underwent exercise right heart catheterization. Exclusion criteria included resting pulmonary arterial or venous hypertension. Receiver operator characteristic curve determined the optimal DLco% cutoffs based on the presence or absence of parenchymal lung disease. Twenty-one (37%) patients had parenchymal lung disease, most common manifesting as chronic obstructive lung disease or interstitial lung disease. In patients with parenchymal lung disease, a DLco of 46% demonstrated 100% sensitivity and 73% specificity for detecting exercise pulmonary hypertension. In patients without parenchymal lung disease, a DLco of 73% demonstrated 58% sensitivity and 94% specificity for detecting exercise pulmonary hypertension. In both cohorts, DLco% below the optimum cutoffs were associated with higher peak mean pulmonary arterial pressure and peak total pulmonary resistance consistent with the hemodynamic definition of exercise pulmonary hypertension. Patients with a DLco < 46% were more often treated with pulmonary vasodilators and had a trend to higher mortality and lung transplant. DLco% is a simple non-invasive screening test for the presence of exercise pulmonary hypertension in our mixed referral population with progressive exertional dyspnea. DLco < 46% with parenchymal lung disease and DLco < 73% without parenchymal lung disease may play a role in differentiating the presence of pulmonary vascular disease prior to invasive hemodynamic testing.

scholarly journals Hepatic Lipid Catabolism via PPARα-Lysosomal Crosstalk

2020 ◽  
Vol 21 (7) ◽  
pp. 2391 ◽  
Author(s):  
Rohit A. Sinha ◽  
Sangam Rajak ◽  
Brijesh K. Singh ◽  
Paul M. Yen
Keyword(s):  
Energy Metabolism ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Reciprocal Regulation ◽  
Alcoholic Fatty Liver ◽  
Lysosomal Activity ◽  
Hepatic Lipid ◽  
Peroxisome Proliferator Activated Receptors ◽  
Key Aspects ◽  
Alcoholic Fatty Liver Disease

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors which belong to the nuclear hormone receptor superfamily. They regulate key aspects of energy metabolism within cells. Recently, PPARα has been implicated in the regulation of autophagy-lysosomal function, which plays a key role in cellular energy metabolism. PPARα transcriptionally upregulates several genes involved in the autophagy-lysosomal degradative pathway that participates in lipolysis of triglycerides within the hepatocytes. Interestingly, a reciprocal regulation of PPARα nuclear action by autophagy-lysosomal activity also exists with implications in lipid metabolism. This review succinctly discusses the unique relationship between PPARα nuclear action and lysosomal activity and explores its impact on hepatic lipid homeostasis under pathological conditions such as non-alcoholic fatty liver disease (NAFLD).

Polyamines and the development of monocrotaline-induced pulmonary hypertension

1984 ◽  
Vol 247 (4) ◽  
pp. H682-H685 ◽  
Author(s):  
J. W. Olson ◽  
A. D. Hacker ◽  
R. J. Altiere ◽  
M. N. Gillespie
Keyword(s):  
Pulmonary Hypertension ◽  
Vascular Disease ◽  
Ventricular Hypertrophy ◽  
Continuous Treatment ◽  
Pulmonary Vascular Disease ◽  
Decarboxylase Activity ◽  
Rat Lung ◽  
Specific Enzyme ◽  
Irreversible Inhibitor ◽  
Adenosylmethionine Decarboxylase

Previous work in our laboratory has shown that the development of monocrotaline-induced pulmonary vascular disease in rats is preceded by a prolonged activation of lung ornithine decarboxylase (ODC). We now report that significant increases in rat lung adenosylmethionine decarboxylase activity and levels of the diamine putrescine and the polyamines, spermidine and spermine, are produced by a single dose of monocrotaline (MCT). Lung putrescine levels were increased from days 7 through 21, and both spermidine and spermine were first elevated at day 10 following MCT administration. This sustained elevation of lung polyamine levels substantially preceded the development of right ventricular hypertrophy and pulmonary hypertension, which were first evident at days 14 and 16, respectively. Continuous treatment with alpha-difluoromethylornithine, a highly specific enzyme-activated, irreversible inhibitor of ODC activity, prevented the development of MCT-induced pulmonary toxicity. It thus appears that ODC and the polyamines may be important mediators of hypertensive pulmonary vascular disease that develops in response to monocrotaline administration.

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