A role for actin polymerization in persistent pulmonary hypertension of the newborn

2015 ◽  
Vol 93 (3) ◽  
pp. 185-194 ◽  
Author(s):  
Jena Fediuk ◽  
Shyamala Dakshinamurti
Keyword(s):  
Pulmonary Hypertension ◽  
Actin Polymerization ◽  
Pulmonary Arteries ◽  
Persistent Pulmonary Hypertension ◽  
Vascular Relaxation ◽  
Cortical Actin ◽  
Actin Isoform ◽  
Pulmonary Arterial

Persistent pulmonary hypertension of the newborn (PPHN) is defined as the failure of normal pulmonary vascular relaxation at birth. Hypoxia is known to impede postnatal disassembly of the actin cytoskeleton in pulmonary arterial myocytes, resulting in elevation of smooth muscle α-actin and γ-actin content in elastic and resistance pulmonary arteries in PPHN compared with age-matched controls. This review examines the original histological characterization of PPHN with attention to cytoskeletal structural remodeling and actin isoform abundance, reviews the existing evidence for understanding the biophysical and biochemical forces at play during neonatal circulatory transition, and specifically addresses the role of the cortical actin architecture, primarily identified as γ-actin, in the transduction of mechanical force in the hypoxic PPHN pulmonary circuit.

scholarly journals Increased TMEM16A-encoded calcium-activated chloride channel activity is associated with pulmonary hypertension

2012 ◽  
Vol 303 (12) ◽  
pp. C1229-C1243 ◽  
Author(s):  
Abigail S. Forrest ◽  
Talia C. Joyce ◽  
Marissa L. Huebner ◽  
Ramon J. Ayon ◽  
Michael Wiwchar ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Electromechanical Coupling ◽  
Pulmonary Arteries ◽  
Doppler Imaging ◽  
Heart Weight ◽  
Channel Activity ◽  
Cl Channels ◽  
Pulmonary Arterial ◽  
Pulmonary Artery Smooth Muscle

Pulmonary artery smooth muscle cells (PASMCs) are more depolarized and display higher Ca2+ levels in pulmonary hypertension (PH). Whether the functional properties and expression of Ca2+-activated Cl− channels (ClCa), an important excitatory mechanism in PASMCs, are altered in PH is unknown. The potential role of ClCa channels in PH was investigated using the monocrotaline (MCT)-induced PH model in the rat. Three weeks postinjection with a single dose of MCT (50 mg/kg ip), the animals developed right ventricular hypertrophy (heart weight measurements) and changes in pulmonary arterial flow (pulse-waved Doppler imaging) that were consistent with increased pulmonary arterial pressure and PH. Whole cell patch experiments revealed an increase in niflumic acid (NFA)-sensitive Ca2+-activated Cl− current [ ICl(Ca)] density in PASMCs from large conduit and small intralobar pulmonary arteries of MCT-treated rats vs. aged-matched saline-injected controls. Quantitative RT-PCR and Western blot analysis revealed that the alterations in ICl(Ca) were accompanied by parallel changes in the expression of TMEM16A, a gene recently shown to encode for ClCa channels. The contraction to serotonin of conduit and intralobar pulmonary arteries from MCT-treated rats exhibited greater sensitivity to nifedipine (1 μM), an l-type Ca2+ channel blocker, and NFA (30 or 100 μM, with or without 10 μM indomethacin to inhibit cyclooxygenases) or T16AInh-A01 (10 μM), TMEM16A/ClCa channel inhibitors, than that of control animals. In conclusion, augmented ClCa/TMEM16A channel activity is a major contributor to the changes in electromechanical coupling of PA in this model of PH. TMEM16A-encoded channels may therefore represent a novel therapeutic target in this disease.

scholarly journals Hypoxia inhibits adenylyl cyclase catalytic activity in a porcine model of persistent pulmonary hypertension of the newborn

2018 ◽  
Vol 315 (6) ◽  
pp. L933-L944 ◽  
Author(s):  
A. S. Sikarwar ◽  
M. Hinton ◽  
K. T. Santhosh ◽  
P. Dhanaraj ◽  
M. Talabis ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Catalytic Activity ◽  
Adenylyl Cyclase ◽  
Specific Activity ◽  
Pulmonary Arteries ◽  
Persistent Pulmonary Hypertension ◽  
Receptor Agonists ◽  
Pulmonary Arterial ◽  
Fraction Of Inspired Oxygen

Persistent pulmonary hypertension of the newborn (PPHN) features hypoxemia, pulmonary vasoconstriction, and impaired cardiac inotropy. We previously reported low basal and stimulated cAMP in hypoxic pulmonary artery smooth muscle cells (PASMCs). We now examine pulmonary arterial adenylyl cyclase (AC) activity and regulation in hypoxic PPHN. PPHN was induced in newborn swine by normobaric hypoxia (fraction of inspired oxygen 0.10) for 72 h and compared with age-matched normoxic controls. We studied relaxation of pulmonary arterial (PA) rings to AC activator forskolin and cGMP activator sodium nitroprusside (SNP) by isometric myography, ATP content, phosphodiesterase activity, AC content, isoform expression, and catalytic activity in presence or absence of Gαs-coupled receptor agonists, forskolin, or transnitrosylating agents in human and neonatal porcine PASMCs and HEK293T stably expressing AC isoform 6, after 72 h hypoxia (10% O2) or normoxia (21% O2). Relaxation to forskolin and SNP were equally impaired in PPHN PA. AC-specific activity decreased in hypoxia. PASMC from PPHN swine had reduced AC activity despite exposure to normoxia in culture; transient hypoxia in vitro further decreased AC activity. Prostacyclin receptor ligand affinity decreased, but its association with Gαs increased in hypoxia. Total AC content was unchanged by hypoxia, but AC6 increased in hypoxic cells and PPHN pulmonary arteries. Impairment of AC6 activity in hypoxia was associated with nitrosylation. PPHN PA relaxation is impaired because of loss of AC activity. Hypoxic AC is inhibited because of S-nitrosylation; inhibition persists after removal from hypoxia. Downregulation of AC-mediated relaxation in hypoxic PA has implications for utility of Gαs-coupled receptor agonists in PPHN treatment.

scholarly journals Endothelial Dysfunction in Pulmonary Hypertension: Cause or Consequence?

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 57
Author(s):  
Kondababu Kurakula ◽  
Valérie F.E.D. Smolders ◽  
Olga Tura-Ceide ◽  
J. Wouter Jukema ◽  
Paul H. A. Quax ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Therapeutic Potential ◽  
Thrombus Formation ◽  
Pulmonary Arteries ◽  
Mesenchymal Transition ◽  
Pulmonary Arterial ◽  
Pulmonary Artery Smooth Muscle ◽  
Endothelial To Mesenchymal Transition ◽  
Molecular Signals

Pulmonary arterial hypertension (PAH) is a rare, complex, and progressive disease that is characterized by the abnormal remodeling of the pulmonary arteries that leads to right ventricular failure and death. Although our understanding of the causes for abnormal vascular remodeling in PAH is limited, accumulating evidence indicates that endothelial cell (EC) dysfunction is one of the first triggers initiating this process. EC dysfunction leads to the activation of several cellular signalling pathways in the endothelium, resulting in the uncontrolled proliferation of ECs, pulmonary artery smooth muscle cells, and fibroblasts, and eventually leads to vascular remodelling and the occlusion of the pulmonary blood vessels. Other factors that are related to EC dysfunction in PAH are an increase in endothelial to mesenchymal transition, inflammation, apoptosis, and thrombus formation. In this review, we outline the latest advances on the role of EC dysfunction in PAH and other forms of pulmonary hypertension. We also elaborate on the molecular signals that orchestrate EC dysfunction in PAH. Understanding the role and mechanisms of EC dysfunction will unravel the therapeutic potential of targeting this process in PAH.

Endothelial cell premature senescence exacerbates pulmonary arterial hypertension through contact-mediated interaction with vascular smooth muscle cells

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Ramadhiani ◽  
K Ikeda ◽  
K Miyagawa ◽  
G.R.T Ryanto ◽  
N Tamada ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Endothelial Cell ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Pulmonary Arteries ◽  
Premature Senescence ◽  
Pulmonary Arterial ◽  
Human Pulmonary Artery

Abstract Introduction Pulmonary arterial hypertension (PAH) is characterized by remodelling and stenosis of the pulmonary arteries, ultimately leading to the right heart failure and death. Endothelial cell (EC) dysfunction is thought to play a central role in the pathogenesis of PAH by mediating the structural changes in pulmonary vasculatures. Various stresses promote premature senescence in EC, which may modify vascular disorders; however, the role of EC senescence in the development of PAH remains poorly understood. Purpose We aimed at investigating the potential role of EC premature senescence in the development of PAH. Methods We recently generated EC-specific progeroid mice in which ECs specifically undergo premature senescence by overexpressing the dominant-negative form of telomere repeat-binding factor 2 (published in Nat Commun 2020). These EC-specific progeroid mice were exposed to hypoxia (10% O2 for three weeks) to induce pulmonary hypertension. Also, we prepared premature senescent ECs using human pulmonary artery ECs (hPAECs) and explored their interaction with human pulmonary artery smooth muscle cells (hPASMCs) in two different conditions; direct and indirect interactions. For indirect coculture, hPASMCs were seeded onto the culture insert, while hPAECs were plated on the culture plate, and they were cocultured in the same well and medium so that secreted factors derived from senescent ECs could access to SMCs through the insert pores. For direct coculture, hPAECs were seeded onto the bottom side of the insert, while hPASMCs were cultured on the top side of the same insert, so that cell-to-cell contact could be made through the pores. Results After chronic hypoxia exposure, the EC-specific progeroid mice showed higher right ventricular systolic pressure and increased right ventricular mass as compared to wild-type (WT) mice, indicating exacerbated pulmonary hypertension. Histological analysis of the lung revealed a significantly enhanced muscularization in the small pulmonary arteries in EC-specific progeroid mice compared to WT mice. Mechanistically, we identified that direct coculture with premature senescent hPAECs enhanced proliferation and migration in hPASMCs, while no such effects were detected in indirect coculture condition. Conclusion To our knowledge, this is the first report that reveals a crucial role of EC premature senescence in the development of PAH. Our in vitro studies suggest that contact-mediated interaction between premature senescent ECs and SMCs is critically involved in its underlying mechanism. Therefore, EC premature senescence is a novel attractive pharmacotherapeutic target for the treatment of PAH. Funding Acknowledgement Type of funding source: None

Abstract MP155: Oxidized Lipids Diet Causes Pulmonary Hypertension Through T-cell Dependent Endothelial Cell Apoptosis

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Gregoire Ruffenach ◽  
Ellen O'connor ◽  
Mylene Vaillancourt ◽  
JASON HONG ◽  
Victor R Grijalva ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Endothelial Cell ◽  
T Cell ◽  
Antigen Processing ◽  
Pulmonary Arteries ◽  
Oxidized Lipids ◽  
Double Positive ◽  
Mimetic Peptide ◽  
Pulmonary Arterial

Background: Pulmonary hypertension (PH) is a fatal disease characterized by an increased mean pulmonary arterial pressure above 25mmHg. This increased pressure is, at least in part, due to thickening of the distal pulmonary arteries. Recently, numerous studies demonstrated an increased plasma concentration of oxidized lipids in PH and in diseases where secondary PH developed. Furthermore, 15-hydroxyeicosatetraenoic acid (15-HETE) an oxidized lipid and a major metabolite of arachidonic acid in the lung, has been implicated in dysregulation of major biological pathways in PH. However, the mechanisms involved in the causal role of 15-HETE in pulmonary hypertension development are not known. Methods and Results: To study the role of 15-HETE in PH development, we fed C57BL6/J mice a diet supplemented with 15-HETE for 3 weeks with no other insults. After 3 weeks on the diet with added 15-HETE, C57BL6/J mice had increased concentrations of not only 15-HETE but also of other oxidized lipids (5-, 11- and 12-HETE) in plasma and lung, and they developed PH. RNA-seq analysis revealed the activation of pathways involved in antigen processing and presentation, and with evidence of T cell mediated cytotoxicity in lungs of mice fed 15-HETE. Transcriptomic profiling of lung tissues obtained from patients with pulmonary arterial hypertension (PAH) demonstrated activation of pathways similar to those seen mice. In mice fed a 15-HETE diet, there was an increase in the number of CD8/CD69 double positive cells, as well as an increase in pulmonary arterial endothelial cell (PAEC) apoptosis. Furthermore, PAEC exposed to 15-HETE were more prone to apoptosis when exposed to CD8 cells. Adding Tg6F, an apoA-I mimetic peptide to the 15-HETE diet prevented and rescued PH in C57BL6/J mice, in part, by inhibiting PAEC apoptosis. Conclusions: 15-HETE diet induced PH in C57Bl6/J mice by triggering PAEC death in a T-cell dependent mechanism. The apoA-I mimetic peptide Tg6F was able to prevent and rescue PH induced by 15-HETE.

scholarly journals Increased hydrogen peroxide downregulates soluble guanylate cyclase in the lungs of lambs with persistent pulmonary hypertension of the newborn

2005 ◽  
Vol 289 (4) ◽  
pp. L660-L666 ◽  
Author(s):  
Stephen Wedgwood ◽  
Robin H. Steinhorn ◽  
Melisa Bunderson ◽  
Jason Wilham ◽  
Satyan Lakshminrusimha ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Pulmonary Hypertension ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Pulmonary Arteries ◽  
Persistent Pulmonary Hypertension ◽  
Ovine Model ◽  
Ros Scavenger ◽  
Pulmonary Arterial ◽  
Initial Objective

Similar to infants born with persistent pulmonary hypertension of the newborn (PPHN), there is an increase in circulating endothelin-1 (ET-1) and decreased cGMP-mediated vasodilation in an ovine model of PPHN. These abnormalities lead to vasoconstriction and vascular remodeling. Our previous studies have demonstrated that reactive oxygen species (ROS) levels are increased in pulmonary arterial smooth muscle cells (PASMC) exposed to ET-1. Thus the initial objective of this study was to determine whether the development of pulmonary hypertension in utero is associated with elevated production of the ROS hydrogen peroxide (H2O2) and if this is associated with alterations in antioxidant capacity. Second we wished to determine whether chronic exposure of PASMC isolated from fetal lambs to H2O2 would mimic the decrease in soluble guanylate cyclase expression observed in the ovine model of PPHN. Our results indicate that H2O2 levels are significantly elevated in pulmonary arteries isolated from 136-day-old fetal PPHN lambs ( P 0.05). In addition, we determined that catalase and glutathione peroxidase expression and activities remain unchanged. Also, we found that the overnight exposure of fetal PASMC to a H2O2-generating system resulted in significant decreases in soluble guanylate cyclase expression and nitric oxide (NO)-dependent cGMP generation ( P 0.05). Finally, we demonstrated that the addition of the ROS scavenger catalase to isolated pulmonary arteries normalized the vasodilator responses to exogenous NO. As these scavengers had no effect on the vasodilator responses in pulmonary arteries isolated from age-matched control lambs this enhancement appears to be unique to PPHN. Overall our data suggest a role for H2O2 in the abnormal vasodilation associated with the pulmonary arteries of PPHN lambs.

Three-week neonatal hypoxia reduces blood CGRP and causes persistent pulmonary hypertension in rats

2000 ◽  
Vol 279 (4) ◽  
pp. H1571-H1578 ◽  
Author(s):  
I. M. Keith ◽  
S. Tjen-A-Looi ◽  
H. Kraiczi ◽  
R. Ekman
Keyword(s):  
Pulmonary Hypertension ◽  
Ventricular Hypertrophy ◽  
Pulmonary Arterial Pressure ◽  
Pulmonary Arteries ◽  
Left Ventricular ◽  
Persistent Pulmonary Hypertension ◽  
Perinatal Exposure ◽  
Calcitonin Gene ◽  
Potent Vasodilator ◽  
Pulmonary Arterial

To increase understanding of persistent pulmonary hypertension, we examined chronic pulmonary effects of hypoxia at birth and their relationships with immunoreactive levels of the potent vasodilator, calcitonin gene-related peptide (CGRP). Rats were born in 10% hypobaric hypoxia, where they remained for 1–2 days, or in 15% hypoxia, where they remained for 21 days. All were then reared in normoxia for 3 mo followed by reexposure to 10% hypoxia for 7 days (H→H) or continued normoxia (H→N); age-matched normoxic rats were hypoxic for the last 7 days (N→H) or normoxic throughout (N→N). Results are as follows. Pulmonary arterial pressure (PPA) in 10% H→N rats was normal at the end of the experiment (13 wk), but in rats reexposed to hypoxia (H→H), pressure rose to 19% above N→H controls. In 15% H→N rats, PPA remained high, similar to that of N→H rats, and increased further by 40% on reexposure (H→H). Medial thickness of small pulmonary arteries in 10% H→H rats also increased by 40% over N→H controls and was equally high in 15% H→N and H→H rats. In N→H rats from both experiments, right ventricular hypertrophy index (RVH) was increased after hypoxia at 15–16 wk. Also, in the 15% study, RVH remained elevated in H→N rats and increased in H→H rats by 19% above N→H controls. Blood CGRP was reduced by neonate and adult hypoxia, and hypoxic reexposure (H→H) further lowered blood CGRP in the 15% but not 10% study. Declining left ventricular blood CGRP correlated highly with logarithmically increasing PPA in the 15% study ( r = −0.81, P = 0.000). In conclusion, 1) short perinatal exposure to 10% O2 exacerbated pulmonary hypertension with hypoxia later in life, 2) 15% O2 at birth and for 21 days caused persistent pulmonary hypertension and exacerbation with reexposure, and 3) PPA correlated highly with declining blood CGRP levels in the 15% study.

scholarly journals Role of the RhoA/ROCK pathway in high-altitude associated neonatal pulmonary hypertension in lambs

2016 ◽  
Vol 310 (11) ◽  
pp. R1053-R1063 ◽  
Author(s):  
Nandy C. Lopez ◽  
German Ebensperger ◽  
Emilio A. Herrera ◽  
Roberto V. Reyes ◽  
Gloria Calaf ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
High Altitude ◽  
Acute Hypoxia ◽  
Pulmonary Arteries ◽  
Rho Kinase ◽  
Daily Administration ◽  
Rock Inhibitor ◽  
Pulmonary Arterial ◽  
Neonatal Lambs

Exposure to high-altitude chronic hypoxia during pregnancy may cause pulmonary hypertension in neonates, as a result of vasoconstriction and vascular remodeling. We hypothesized that susceptibility to pulmonary hypertension, due to an augmented expression and activity of the RhoA/Rho-kinase (ROCK) pathway in these neonates, can be reduced by daily administration of fasudil, a ROCK inhibitor. We studied 10 highland newborn lambs with conception, gestation, and birth at 3,600 m in Putre, Chile. Five highland controls (HLC) were compared with 5 highland lambs treated with fasudil (HL-FAS; 3 mg·kg−1·day−1 iv for 10 days). Ten lowland controls were studied in Lluta (50 m; LLC). During the 10 days of fasudil daily administration, the drug decreased pulmonary arterial pressure (PAP) and resistance (PVR), basally and during a superimposed episode of acute hypoxia. HL-FAS small pulmonary arteries showed diminished muscular area and a reduced contractile response to the thromboxane analog U46619 compared with HLC. Hypoxia, but not fasudil, changed the protein expression pattern of the RhoA/ROCKII pathway. Moreover, HL-FAS lungs expressed less pMYPT1T850 and pMYPT1T696 than HLC, with a potential increase of the myosin light chain phosphatase activity. Finally, hypoxia induced RhoA, ROCKII, and PKG mRNA expression in PASMCs of HLC, but fasudil reduced them (HL-FAS) similarly to LLC. We conclude that fasudil decreases the function of the RhoA/ROCK pathway, reducing the PAP and PVR in chronically hypoxic highland neonatal lambs. The inhibition of ROCKs by fasudil may offer a possible therapeutic tool for the pulmonary hypertension of the neonates.

scholarly journals Reduced membrane cholesterol limits pulmonary endothelial Ca2+ entry after chronic hypoxia

2017 ◽  
Vol 312 (6) ◽  
pp. H1176-H1184 ◽  
Author(s):  
Bojun Zhang ◽  
Jay S. Naik ◽  
Nikki L. Jernigan ◽  
Benjimen R. Walker ◽  
Thomas C. Resta
Keyword(s):  
Pulmonary Hypertension ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Barometric Pressure ◽  
Membrane Cholesterol ◽  
Potential Mechanism ◽  
Direct Role ◽  
Pulmonary Arterial ◽  
Arterial Endothelial Cells

Chronic hypoxia (CH)-induced pulmonary hypertension is associated with diminished production of endothelium-derived Ca2+-dependent vasodilators such as nitric oxide. Interestingly, ATP-induced endothelial Ca2+ entry as well as membrane cholesterol (Chol) are decreased in pulmonary arteries from CH rats (4 wk, barometric pressure = 380 Torr) compared with normoxic controls. Store-operated Ca2+ entry (SOCE) and depolarization-induced Ca2+ entry are major components of the response to ATP and are similarly decreased after CH. We hypothesized that membrane Chol facilitates both SOCE and depolarization-induced pulmonary endothelial Ca2+ entry and that CH attenuates these responses by decreasing membrane Chol. To test these hypotheses, we administered Chol or epicholesterol (Epichol) to acutely isolated pulmonary arterial endothelial cells (PAECs) from control and CH rats to either supplement or replace native Chol, respectively. The efficacy of membrane Chol manipulation was confirmed by filipin staining. Epichol greatly reduced ATP-induced Ca2+ influx in PAECs from control rats. Whereas Epichol similarly blunted endothelial SOCE in PAECs from both groups, Chol supplementation restored diminished SOCE in PAECs from CH rats while having no effect in controls. Similar effects of Chol manipulation on PAEC Ca2+ influx were observed in response to a depolarizing stimulus of KCl. Furthermore, KCl-induced Ca2+ entry was inhibited by the T-type Ca2+ channel antagonist mibefradil but not the L-type Ca2+ channel inhibitor diltiazem. We conclude that PAEC membrane Chol is required for ATP-induced Ca2+ entry and its two components, SOCE and depolarization-induced Ca2+ entry, and that reduced Ca2+ entry after CH may be due to loss of this key regulator. NEW & NOTEWORTHY This research is the first to examine the direct role of membrane cholesterol in regulating pulmonary endothelial agonist-induced Ca2+ entry and its components. The results provide a potential mechanism by which chronic hypoxia impairs pulmonary endothelial Ca2+ influx, which may contribute to pulmonary hypertension.

scholarly journals Endothelial Basement Membrane Components and Their Products, Matrikines: Active Drivers of Pulmonary Hypertension?

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2029
Author(s):  
Ayse Ceren Mutgan ◽  
Katharina Jandl ◽  
Grazyna Kwapiszewska
Keyword(s):  
Pulmonary Hypertension ◽  
Basement Membrane ◽  
Vascular Remodeling ◽  
Pulmonary Arteries ◽  
Biologically Active ◽  
Pulmonary Arterial ◽  
And Migration ◽  
Endothelial Basement Membrane ◽  
Membrane Components

Pulmonary arterial hypertension (PAH) is a vascular disease that is characterized by elevated pulmonary arterial pressure (PAP) due to progressive vascular remodeling. Extracellular matrix (ECM) deposition in pulmonary arteries (PA) is one of the key features of vascular remodeling. Emerging evidence indicates that the basement membrane (BM), a specialized cluster of ECM proteins underlying the endothelium, may be actively involved in the progression of vascular remodeling. The BM and its steady turnover are pivotal for maintaining appropriate vascular functions. However, the pathologically elevated turnover of BM components leads to an increased release of biologically active short fragments, which are called matrikines. Both BM components and their matrikines can interfere with pivotal biological processes, such as survival, proliferation, adhesion, and migration and thus may actively contribute to endothelial dysfunction. Therefore, in this review, we summarize the emerging role of the BM and its matrikines on the vascular endothelium and further discuss its implications on lung vascular remodeling in pulmonary hypertension.

Sign in / Sign up

Export Citation Format

Share Document