scholarly journals Senescence Alterations in Pulmonary Hypertension

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3456
Author(s):  
Inés Roger ◽  
Javier Milara ◽  
Nada Belhadj ◽  
Julio Cortijo
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Cellular Senescence ◽  
Chronic Obstructive ◽  
Aged Patients ◽  
Obstructive Pulmonary Disease ◽  
Artery Remodeling ◽  
Cell Phenotypes ◽  
Pulmonary Artery Remodeling

Cellular senescence is the arrest of normal cell division and is commonly associated with aging. The interest in the role of cellular senescence in lung diseases derives from the observation of markers of senescence in chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (IPF), and pulmonary hypertension (PH). Accumulation of senescent cells and the senescence-associated secretory phenotype in the lung of aged patients may lead to mild persistent inflammation, which results in tissue damage. Oxidative stress due to environmental exposures such as cigarette smoke also promotes cellular senescence, together with additional forms of cellular stress such as mitochondrial dysfunction and endoplasmic reticulum stress. Growing recent evidence indicate that senescent cell phenotypes are observed in pulmonary artery smooth muscle cells and endothelial cells of patients with PH, contributing to pulmonary artery remodeling and PH development. In this review, we analyze the role of different senescence cell phenotypes contributing to the pulmonary artery remodeling process in different PH clinical entities. Different molecular pathway activation and cellular functions derived from senescence activation will be analyzed and discussed as promising targets to develop future senotherapies as promising treatments to attenuate pulmonary artery remodeling in PH.

scholarly journals Loss of family with sequence similarity 13, member A exacerbates pulmonary hypertension through accelerating endothelial-to-mesenchymal transition

2019 ◽  
Author(s):  
Pranindya Rinastiti ◽  
Koji Ikeda ◽  
Elda Putri Rahardini ◽  
Kazuya Miyagawa ◽  
Naoki Tamada ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Sequence Similarity ◽  
Genome Wide Association Studies ◽  
Mesenchymal Transition ◽  
Artery Remodeling ◽  
Endothelial To Mesenchymal Transition ◽  
Pulmonary Artery Remodeling

AbstractPulmonary hypertension is a progressive lung disease with poor prognosis due to the consequent right heart ventricular failure. Pulmonary artery remodeling and dysfunction are culprits for pathologically increased pulmonary arterial pressure, but their underlying molecular mechanisms remain to be elucidated. Previous genome-wide association studies revealed a significant correlation between the genetic locus of family with sequence similarity 13, member A (FAM13A) and various lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis; however whether FAM13A is also involved in the pathogenesis of pulmonary hypertension remained unknown. Here, we identified a significant role of FAM13A in the development of pulmonary hypertension. FAM13A expression was reduced in mouse lungs of hypoxia-induced pulmonary hypertension model. We identified that FAM13A was expressed in lung vasculatures, especially in endothelial cells. Genetic loss of FAM13A exacerbated pulmonary hypertension in mice exposed to chronic hypoxia in association with deteriorated pulmonary artery remodeling. Mechanistically, FAM13A decelerated endothelial-to-mesenchymal transition potentially by inhibiting β-catenin signaling in pulmonary artery endothelial cells. Our data revealed a protective role of FAM13A in the development of pulmonary hypertension, and therefore increasing and/or preserving FAM13A expression in pulmonary artery endothelial cells is an attractive therapeutic strategy for the treatment of pulmonary hypertension.

scholarly journals The Role of JAK/STAT Molecular Pathway in Vascular Remodeling Associated with Pulmonary Hypertension

2021 ◽  
Vol 22 (9) ◽  
pp. 4980
Author(s):  
Inés Roger ◽  
Javier Milara ◽  
Paula Montero ◽  
Julio Cortijo
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Vascular Remodeling ◽  
Pulmonary Arteries ◽  
Clinical Manifestations ◽  
Different Types ◽  
Artery Remodeling ◽  
Stat Pathway ◽  
Pulmonary Artery Remodeling

Pulmonary hypertension is defined as a group of diseases characterized by a progressive increase in pulmonary vascular resistance (PVR), which leads to right ventricular failure and premature death. There are multiple clinical manifestations that can be grouped into five different types. Pulmonary artery remodeling is a common feature in pulmonary hypertension (PH) characterized by endothelial dysfunction and smooth muscle pulmonary artery cell proliferation. The current treatments for PH are limited to vasodilatory agents that do not stop the progression of the disease. Therefore, there is a need for new agents that inhibit pulmonary artery remodeling targeting the main genetic, molecular, and cellular processes involved in PH. Chronic inflammation contributes to pulmonary artery remodeling and PH, among other vascular disorders, and many inflammatory mediators signal through the JAK/STAT pathway. Recent evidence indicates that the JAK/STAT pathway is overactivated in the pulmonary arteries of patients with PH of different types. In addition, different profibrotic cytokines such as IL-6, IL-13, and IL-11 and growth factors such as PDGF, VEGF, and TGFβ1 are activators of the JAK/STAT pathway and inducers of pulmonary remodeling, thus participating in the development of PH. The understanding of the participation and modulation of the JAK/STAT pathway in PH could be an attractive strategy for developing future treatments. There have been no studies to date focused on the JAK/STAT pathway and PH. In this review, we focus on the analysis of the expression and distribution of different JAK/STAT isoforms in the pulmonary arteries of patients with different types of PH. Furthermore, molecular canonical and noncanonical JAK/STAT pathway transactivation will be discussed in the context of vascular remodeling and PH. The consequences of JAK/STAT activation for endothelial cells and pulmonary artery smooth muscle cells’ proliferation, migration, senescence, and transformation into mesenchymal/myofibroblast cells will be described and discussed, together with different promising drugs targeting the JAK/STAT pathway in vitro and in vivo.

scholarly journals Pulmonary artery size as a predictor of pulmonary hypertension and outcomes in patients with chronic obstructive pulmonary disease

2014 ◽  
Vol 108 (11) ◽  
pp. 1626-1632 ◽  
Author(s):  
Stephanie Shin ◽  
Christopher S. King ◽  
A. Whitney Brown ◽  
Maria C. Albano ◽  
Melany Atkins ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

scholarly journals Comorbid patient with chronic obstructive pulmonary disease and coronary heart disease: opportunities for early diagnosis of pulmonary hypertension in outpatient settings

2021 ◽  
pp. 146-153
Author(s):  
D. N. Kalashnik ◽  
I. S. Korolchuk
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Hypertension ◽  
Cardiovascular Diseases ◽  
Angina Pectoris ◽  
Pulmonary Artery ◽  
Pulmonary Disease ◽  
Right Atrium ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
The Right

Introduction. A comorbid patient with the chronic obstructive pulmonary disease (COPD) in combination with cardiovascular diseases (CHD) has a poor prognosis due to the early progression of the pulmonary hypertension (PH). The study surveyed an opportunity of the PH detection using an active PH verification strategy in outpatients with COPD and stable angina pectoris.Goal. To evaluate the frequency of РH in patients with mild and moderate COPD in combination with CHD and the possibility of using the echocardiographic criterion «right atrial area» to prove РH.Materials and methods. The study included 52 outpatient patients with an average age of 62.8 ± 8.14 years. A comprehensive assessment of the Borg dyspnea scale, echocardiography, pulse oximetry at rest and after the 6-minute walk test (6MWT) were carried out. Two groups of patients were compared depending on the development of РH after T6MX.Results and discussion. It was shown that in patients with COPD (GOLD I-II) and angina pectoris, PH was initially detected in 3.3% of cases, and after the 6MWT in 63.3% of patients. In this group, after T6MX, an increase in pulmonary artery pressure was determined from 18.5 ± 10.6 mmHg to 41.2 ± 12.5 mmHg (p < 0.05). After physical activity with increased pressure in the pulmonary artery, there was a significant increase in the area of the right atrium. Only 1/3 of patients with PH had hypoxemia after the 6MWT.Conclusions. The T6M test makes it possible to detect РH in more than half of patients with COPD (GOLD I-II) and CHD in an outpatient setting. An enlargement in the area of the right atrium according to echocardiography, along with the other indicators of morphological and functional changes in the right heart, can be an additional diagnostic criterion for PH in comorbid patients with COPD and cardiovascular diseases. 

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