scholarly journals Early onset of retrograde flow in the main pulmonary artery is a characteristic of pulmonary arterial hypertension

2011 ◽  
Vol 33 (6) ◽  
pp. 1362-1368 ◽  
Author(s):  
Frank Helderman ◽  
Gert-Jan Mauritz ◽  
Kirsten E. Andringa ◽  
Anton Vonk-Noordegraaf ◽  
J. Tim Marcus
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Early Onset ◽  
Main Pulmonary Artery ◽  
Retrograde Flow ◽  
Pulmonary Arterial

Regional Biomechanical and Microstructural Alterations of the Ovine Main Pulmonary Artery During Postnatal Growth

2012 ◽  
Author(s):  
Bahar Fata ◽  
Christopher A. Carruthers ◽  
Gregory A. Gibson ◽  
Simon C. Watkins ◽  
Danielle Gottlieb ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Congenital Heart ◽  
Main Pulmonary Artery ◽  
Postnatal Growth ◽  
Tissue Mechanics ◽  
Microstructural Alterations ◽  
Native Tissue ◽  
Pulmonary Arterial

It has been estimated that worldwide 600,000 babies are born annually with significant congenital heart disease (1). Congenital heart and related vascular defects cause increased flow and pulmonary pressure leading to unfavorable vascular remodeling that results in pulmonary arterial hypertension (1). Developing tissue engineered replacements that mimic the growth and remodeling behavior of native tissue is the optimal approach in treatment of congenital arterial anomalies. The understanding of the underlying mechanisms leading to pulmonary arterial hypertension as well as replicating native pulmonary artery functionality in engineered replacements requires knowledge of native tissue mechanics and growth behavior. In the present study, we report novel information on the changes in the structure-mechanics behavior of the growing pulmonary artery.

Progressive Dilatation of the Main Pulmonary Artery Is a Characteristic of Pulmonary Arterial Hypertension and Is Not Related to Changes in Pressure

CHEST Journal ◽  
2010 ◽  
Vol 138 (6) ◽  
pp. 1395-1401 ◽  
Author(s):  
Bart Boerrigter ◽  
Gert-Jan Mauritz ◽  
J. Tim Marcus ◽  
Frank Helderman ◽  
Pieter E. Postmus ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Main Pulmonary Artery ◽  
Pulmonary Arterial

scholarly journals Pulmonary Arterial Hypertension Induced by Distention of the Main Pulmonary Artery in Conscious Newborn, Young, and Adult Sheep

1980 ◽  
Vol 14 (12) ◽  
pp. 1332-1338 ◽  
Author(s):  
Craig E Juratsch ◽  
George C Emmanouilides ◽  
Donald W Thibeault ◽  
Barry G Baylen ◽  
James A Jengo ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Main Pulmonary Artery ◽  
Adult Sheep ◽  
Pulmonary Arterial

scholarly journals LRP1 Deficiency in Vascular SMC Leads to Pulmonary Arterial Hypertension That Is Reversed by PPARγ Activation

2019 ◽  
Vol 124 (12) ◽  
pp. 1778-1785 ◽  
Author(s):  
Laurent Calvier ◽  
Philippe Boucher ◽  
Joachim Herz ◽  
Georg Hansmann
Keyword(s):  
Growth Factor ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Main Pulmonary Artery ◽  
Tissue Growth ◽  
Pulmonary Vasculature ◽  
Pparγ Agonist ◽  
Pulmonary Arterial ◽  
Human Pulmonary Artery

Rationale: Arterial remodeling—a hallmark of many cardiovascular pathologies including pulmonary arterial hypertension (PAH)—is regulated by TGFβ1 (transforming growth factor-β1)–TGFβ receptors and the antagonistic, vasoprotective BMPR2 (bone morphogenetic protein receptor 2)–PPARγ (peroxisome proliferator–activated receptor-γ) axis. However, it is unclear which factors drive detrimental TGFβ1 pathways in the hypertensive pulmonary vasculature. Objective: We hypothesized that LRP1 (low-density lipoprotein receptor–related protein 1) expression is decreased in PAH, leading to enhancement (disinhibition) of TGFβ1 signals and that the PPARγ agonist pioglitazone can restore vascular homeostasis and prevent PAH resulting from LRP1 deletion in vascular smooth muscle cells (SMCs). Methods and Results: Targeted deletion of LRP1 in vascular SMC (smLRP1 −/− ) in mice disinhibited TGFβ1–CTGF (connective tissue growth factor) signaling, leading to spontaneous PAH and distal pulmonary arterial muscularization as assessed by closed-chest cardiac catheterization and anti-αSMA staining. Pioglitazone inhibited the canonical TGFβ1–CTGF axis in human pulmonary artery SMC and smLRP1 −/− main pulmonary artery (CTGF and NOX4) and reversed PAH in smLRP1 −/− mice. TGFβ1 boosted pSmad3 in PASMC from smLRP1 −/− mice versus controls. Pioglitazone-activated PPARγ binds to Smad3 in human pulmonary artery SMC (coimmunoprecipitation), thereby blocking its phosphorylation and overriding LRP1 deficiency. Finally, mRNA and protein expression of LRP1 was decreased in pulmonary plexiform lesions of patients with end-stage idiopathic PAH (laser capture microdissection, qPCR, and immunohistochemistry). Downregulation of LRP1 protein was also demonstrated in explanted PASMC from patients with PAH and accompanied by enhanced TGFβ1–pSmad3–CTGF signaling and increased TGFβ1–induced PASMC proliferation that was prevented by pioglitazone. Conclusions: Here, we identify LRP1 as an integrator of TGFβ1–mediated mechanisms that regulate vascular remodeling in mice and clinical PAH and PPARγ as a therapeutic target that controls canonical TGFβ1 pathways. Hence, pharmacologic PPARγ activation represents a promising new therapy for patients with PAH who lack the vasoprotective LRP1 in vascular SMC.

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