Right ventricular systolic pressure by echocardiography as a predictor of pulmonary hypertension in idiopathic pulmonary fibrosis

2009 ◽  
Vol 2009 ◽  
pp. 206-207
Author(s):  
M. Ali Raza
Keyword(s):  
Pulmonary Hypertension ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Right Ventricular ◽  
Systolic Pressure ◽  
Right Ventricular Systolic Pressure ◽  
Ventricular Systolic Pressure

scholarly journals Chronic Hypoxia Decreases Endothelial Connexin 40, Attenuates Endothelium‐Dependent Hyperpolarization–Mediated Relaxation in Small Distal Pulmonary Arteries, and Leads to Pulmonary Hypertension

2020 ◽  
Vol 9 (24) ◽  
Author(s):  
Rui Si ◽  
Qian Zhang ◽  
Jody Tori O. Cabrera ◽  
Qiuyu Zheng ◽  
Atsumi Tsuji‐Hosokawa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Knockout Mice ◽  
Chronic Hypoxia ◽  
Systolic Pressure ◽  
Right Ventricular Systolic Pressure ◽  
Ventricular Systolic Pressure ◽  
Pulmonary Endothelial Cells ◽  
Endothelium Dependent Relaxation

Background Abnormal endothelial function in the lungs is implicated in the development of pulmonary hypertension; however, there is little information about the difference of endothelial function between small distal pulmonary artery (PA) and large proximal PA and their contribution to the development of pulmonary hypertension. Herein, we investigate endothelium‐dependent relaxation in different orders of PAs and examine the molecular mechanisms by which chronic hypoxia attenuates endothelium‐dependent pulmonary vasodilation, leading to pulmonary hypertension. Methods and Results Endothelium‐dependent relaxation in large proximal PAs (second order) was primarily caused by releasing NO from the endothelium, whereas endothelium‐dependent hyperpolarization (EDH)–mediated vasodilation was prominent in small distal PAs (fourth–fifth order). Chronic hypoxia abolished EDH‐mediated relaxation in small distal PAs without affecting smooth muscle–dependent relaxation. RNA‐sequencing data revealed that, among genes related to EDH, the levels of Cx37 , Cx40 , Cx43 , and IK were altered in mouse pulmonary endothelial cells isolated from chronically hypoxic mice in comparison to mouse pulmonary endothelial cells from normoxic control mice. The protein levels were significantly lower for connexin 40 (Cx40) and higher for connexin 37 in mouse pulmonary endothelial cells from hypoxic mice than normoxic mice. Cx40 knockout mice exhibited significant attenuation of EDH‐mediated relaxation and marked increase in right ventricular systolic pressure. Interestingly, chronic hypoxia led to a further increase in right ventricular systolic pressure in Cx40 knockout mice without altering EDH‐mediated relaxation. Furthermore, overexpression of Cx40 significantly decreased right ventricular systolic pressure in chronically hypoxic mice. Conclusions These data suggest that chronic hypoxia‐induced downregulation of endothelial Cx40 results in impaired EDH‐mediated relaxation in small distal PAs and contributes to the development of pulmonary hypertension.

scholarly journals NFATc3 is required for chronic hypoxia-induced pulmonary hypertension in adult and neonatal mice

2011 ◽  
Vol 301 (6) ◽  
pp. L872-L880 ◽  
Author(s):  
R. Bierer ◽  
C. H. Nitta ◽  
J. Friedman ◽  
S. Codianni ◽  
S. de Frutos ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Vascular Remodeling ◽  
Ventricular Hypertrophy ◽  
Chronic Hypoxia ◽  
Systolic Pressure ◽  
Right Ventricular Systolic Pressure ◽  
Ventricular Systolic Pressure ◽  
Neonatal Mice ◽  
Adult Mice

Pulmonary hypertension occurs with prolonged exposure to chronic hypoxia in both adults and neonates. The Ca2+-dependent transcription factor, nuclear factor of activated T cells isoform c3 (NFATc3), has been implicated in chronic hypoxia-induced pulmonary arterial remodeling in adult mice. Therefore, we hypothesized that NFATc3 is required for chronic hypoxia-induced pulmonary hypertension in adult and neonatal mice. The aim of this study was to determine whether 1) NFATc3 mediates chronic hypoxia-induced increases in right ventricular systolic pressure in adult mice; 2) NFATc3 is activated in neonatal mice exposed to chronic hypoxia; and 3) NFATc3 is involved in chronic hypoxia-induced right ventricular hypertrophy and pulmonary vascular remodeling in neonatal mice. Adult mice were exposed to hypobaric hypoxia for 2, 7, and 21 days. Neonatal mouse pups were exposed for 7 days to hypobaric chronic hypoxia within 2 days after delivery. Hypoxia-induced increases in right ventricular systolic pressure were absent in NFATc3 knockout adult mice. In neonatal mice, chronic hypoxia caused NFAT activation in whole lung and nuclear accumulation of NFATc3 in both pulmonary vascular smooth muscle and endothelial cells. In addition, heterozygous NFATc3 neonates showed less right ventricular hypertrophy and pulmonary artery wall thickness in response to chronic hypoxia than did wild-type neonates. Our results suggest that NFATc3 mediates pulmonary hypertension and vascular remodeling in both adult and neonatal mice.

Abstract 2302: Adeno-associated Virus-mediated Prostaglandin I Synthase Gene Transfer Improved The Hypoxia-induced Pulmonary Hypertension In Mice

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Takashi Kawakami ◽  
Hideaki Kanazawa ◽  
Toru Satoh ◽  
Masaki Ieda ◽  
Yasuyo Ieda ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Gene Transfer ◽  
Right Ventricular ◽  
Histological Analysis ◽  
Systolic Pressure ◽  
Thigh Muscle ◽  
Control Group ◽  
Right Ventricular Systolic Pressure ◽  
Adeno Associated Virus ◽  
Ventricular Systolic Pressure

Background: Although prostaglandin I 2 and its derivatives are clinically used for the treatment of pulmonary hypertension, continuous intravenous administration is required for the effective treatment. Prostaglandin I 2 synthase (PGIS) is one of the most powerful therapeutic genes against pulmonary hypertension (PH). The purpose of this study was to investigate whether the human PGIS (hPGIS) gene transfer using adeno-associated virus (AAV) vector into the skeletal muscle was effective to the hypoxia induced-pulmonary hypertension in mice. Methods and Results: PH was induced in the mice subjected to hypoxic chamber (O2 10%) for 8 weeks. Right ventricular systolic pressure (RVSP) significantly increased in PH group compared with control group. In the gene transferred group (AAV1-hPGIS), the AAV type1-hPGIS (2.0×10 11 v.g./body) vector was injected into the left thigh muscle at 24 hour after exposure to hypoxia. Saline injected mice were served as control group. After 8 weeks, hemodynamics and histological analysis was performed. AAV1-PGIS significantly decreased right ventricular systolic pressure to 26±5 mmHg compared with PH group (40±4 mmHg). Systemic blood pressure did not significantly decrease AAV-hPGIS treated group. QT-PCR revealed that PH group increased BNP mRNA in RV by 6-fold higher, while AAV1-hPGIS group decreased to 1.3-fold compared with the control group. Histological analysis revealed that PH group showed severe medial thickening of the pulmonary artery, and increased %wall thickness to 33.3±7.3%, while AAV1-hPGIS decreased to 17±3.6 %. RT-PCR revealed that the hPGIS gene expression was detected only at the injected side, but not in the liver, kidney, heart, and the other organs. Histological analysis showed no pathological changes at the injected skeletal muscles. Finally, Kaplan-Mayer analysis revealed that PH group showed 47% survival at 12 weeks wile AAV1-hPGIS group showed 73%, indicating that AAV1-hPGIS treatment significantly increased the survival of PH. Conclusions: Our study demonstrated that the AAV1-mediaqted gene transfer of PGIS was effective to treat the hypoxia-induced pulmonary hypertension in mice, and can prolong the survival of these animals.

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