Pulmonary Artery Pulse Wave Velocity in Idiopathic Pulmonary Arterial Hypertension

2013 ◽  
Vol 29 (6) ◽  
pp. 683-690 ◽  
Author(s):  
Grzegorz Kopeć ◽  
Deddo Moertl ◽  
Piotr Jankowski ◽  
Anna Tyrka ◽  
Bartosz Sobień ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Pulse Wave Velocity ◽  
Arterial Hypertension ◽  
Wave Velocity ◽  
Pulse Wave ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Pulmonary Arterial

Upregulation of Na+/Ca2+ exchanger contributes to the enhanced Ca2+ entry in pulmonary artery smooth muscle cells from patients with idiopathic pulmonary arterial hypertension

2007 ◽  
Vol 292 (6) ◽  
pp. C2297-C2305 ◽  
Author(s):  
Shen Zhang ◽  
Hui Dong ◽  
Lewis J. Rubin ◽  
Jason X.-J. Yuan
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Smooth Muscle Cells ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Reverse Mode ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial ◽  
Pulmonary Artery Smooth Muscle

A rise in cytosolic Ca2+ concentration ([Ca2+]cyt) in pulmonary artery smooth muscle cells (PASMC) is a trigger for pulmonary vasoconstriction and a stimulus for PASMC proliferation and migration. Multiple mechanisms are involved in regulating [Ca2+]cyt in human PASMC. The resting [Ca2+]cyt and Ca2+ entry are both increased in PASMC from patients with idiopathic pulmonary arterial hypertension (IPAH), which is believed to be a critical mechanism for sustained pulmonary vasoconstriction and excessive pulmonary vascular remodeling in these patients. Here we report that protein expression of NCX1, an NCX family member of Na+/Ca2+ exchanger proteins is upregulated in PASMC from IPAH patients compared with PASMC from normal subjects and patients with other cardiopulmonary diseases. The Na+/Ca2+ exchanger operates in a forward (Ca2+ exit) and reverse (Ca2+ entry) mode. By activating the reverse mode of Na+/Ca2+ exchange, removal of extracellular Na+ caused a rapid increase in [Ca2+]cyt, which was significantly enhanced in IPAH PASMC compared with normal PASMC. Furthermore, passive depletion of intracellular Ca2+ stores using cyclopiazonic acid (10 μM) not only caused a rise in [Ca2+]cyt due to Ca2+ influx through store-operated Ca2+ channels but also mediated a rise in [Ca2+]cyt via the reverse mode of Na+/Ca2+ exchange. The upregulated NCX1 in IPAH PASMC led to an enhanced Ca2+ entry via the reverse mode of Na+/Ca2+ exchange, but did not accelerate Ca2+ extrusion via the forward mode of Na+/Ca2+ exchange. These observations indicate that the upregulated NCX1 and enhanced Ca2+ entry via the reverse mode of Na+/Ca2+ exchange are an additional mechanism responsible for the elevated [Ca2+]cyt in PASMC from IPAH patients.

Clinical impact of subcutaneous treprostinil in trisomy 21 patient with pulmonary arterial hypertension associated with CHD

2022 ◽  
pp. 1-3
Author(s):  
Ryusuke Numata ◽  
Kiyohiro Takigiku ◽  
Kouta Takei
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Exercise Capacity ◽  
Trisomy 21 ◽  
Pulmonary Artery Hypertension ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Clinical Impact ◽  
Pulmonary Arterial ◽  
Hypertension In Children

Abstract Subcutaneous treprostinil is commonly used to improve idiopathic pulmonary arterial hypertension in children. However, its effectiveness has not been reported in trisomy 21. We report the case of 9-year-old boy in trisomy 21 with CHD-pulmonary artery hypertension after surgical correction of CHD. Haemodynamics and exercise capacity dramatically improved with a transition from oral selexipag to subcutaneous treprostinil.

Abstract 379: Enhancement of TRPC6-mediated Ca 2+ Entry in Pulmonary Artery Smooth Muscle Cells of Idiopathic Pulmonary Arterial Hypertension Patients

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Ying Yu ◽  
Olga Safrina ◽  
Oleksandr Platoshyn ◽  
Michael D Cahalan ◽  
Lewis J Rubin ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Pulmonary Arterial ◽  
Pulmonary Artery Smooth Muscle ◽  
Excessive Proliferation

Background & Hypothesis: Excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) and sustained pulmonary vasoconstriction are thought to play critical roles in the development of idiopathic pulmonary arterial hypertension (IPAH). Recently, we demonstrated that upregulation of the canonical transient receptor potential 6 (TRPC6) channel contributes to excessive proliferation of PASMCs isolated from IPAH patients. This study aimed at characterizing whether up-regulated TRPC6 expression affects resting cytosolic [Ca 2+ ] ([Ca 2+ ] cyt ) level and Ca 2+ entry in PASMCs of IPAH patients. Methods & Results: [Ca 2+ ] cyt was measured by fluorescence ratio video imaging with the Ca 2+ indicator fura-2. 1-Oleoyl-2-acetyl-sn-glycerol (OAG), a cell-permeable diacylglycerol analog that activates TRPC6 channels, was used to stimulate channel activities in the presence of extracellular Ca 2+ . The resting [Ca 2+ ] cyt andOAG-mediated increase in [Ca 2+ ]cyt were significantly higher in PASMCs from IPAH patients compared to PASMCs isolated from secondary pulmonary artery hypertension and normotensive patients. In PASMCs from IPAH patients, inhibition of TRPC6 expression by adenovirus-mediated siRNA specifically targeted the human TRPC6 gene led to an approximately 90% reduction of TRPC6 mRNA and protein levels and significantly attenuated OAG-mediated increase in [Ca 2+ ] cyt . Treatment of the IPAH-PASMCs with siRNA also decreased the resting [Ca 2+ ] cyt and significantly inhibited cell proliferation in comparison to cells treated with scrambled control siRNA. Furthermore, exogenous overexpression of human TRPC6 increased the resting [Ca 2+ ] cyt and enhanced OAG-mediated Ca 2+ entry in normal PASMCs. C onclusions: These results suggest that upregulation of TRPC6 channels in PASMC from IPAH patients serves as an important pathway for agonist-mediated Ca 2+ entry, mitogen-mediated PASMC proliferation and, ultimately, pulmonary vascular remodeling. Targeting TRPC6 expression and function in PASMCs would help develop novel therapeutic approaches for IPAH patients.

scholarly journals Pulmonary Pulse Wave Transit Time is Associated with Right Ventricular–Pulmonary Artery Coupling in Pulmonary Arterial Hypertension

2016 ◽  
Vol 6 (4) ◽  
pp. 576-585 ◽  
Author(s):  
Kurt W. Prins ◽  
E. Kenneth Weir ◽  
Stephen L. Archer ◽  
Jeremy Markowitz ◽  
Lauren Rose ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Transit Time ◽  
Pulse Wave ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Pulse Wave Transit Time ◽  
Pulmonary Arterial

Pulmonary pulse wave transit time (pPTT), defined as the time for the systolic pressure pulse wave to travel from the pulmonary valve to the pulmonary veins, has been reported to be reduced in pulmonary arterial hypertension (PAH); however, the underlying mechanism of reduced pPTT is unknown. Here, we investigate the hypothesis that abbreviated pPTT in PAH results from impaired right ventricular–pulmonary artery (RV-PA) coupling. We quantified pPTT using pulsed-wave Doppler ultrasound from 10 healthy age- and sex-matched controls and 36 patients with PAH. pPTT was reduced in patients with PAH compared with controls. Univariate analysis revealed the following significant predictors of reduced pPTT: age, right ventricular fractional area change (RV FAC), tricuspid annular plane excursion (TAPSE), pulmonary arterial pressures (PAP), diastolic pulmonary gradient, transpulmonary gradient, pulmonary vascular resistance, and RV-PA coupling (defined as RV FAC/mean PAP or TAPSE/mean PAP). Although the correlations between pPTT and invasive markers of pulmonary vascular disease were modest, RV FAC ( r = 0.64, P < 0.0001), TAPSE ( r = 0.67, P < 0.0001), and RV-PA coupling (RV FAC/mean PAP: r = 0.72, P < 0.0001; TAPSE/mean PAP: r = 0.74, P < 0.0001) had the strongest relationships with pPTT. On multivariable analysis, only RV FAC, TAPSE, and RV-PA coupling were independent predictors of pPTT. We conclude that shortening of pPTT in patients with PAH results from altered RV-PA coupling, probably occurring as a result of reduced pulmonary arterial compliance. Thus, pPTT allows noninvasive determination of the status of both the pulmonary vasculature and the response of the RV in patients with PAH, thereby allowing monitoring of disease progression and regression.

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