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Pulmonary Arterial Hypertension: From Molecular Mechanisms to Novel Therapeutic Approaches

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 January 2025 | Viewed by 1289

Special Issue Editors


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Guest Editor
Universities of Giessen and Marburg Lung Center (UGMLC), Excellence Cluster Cardio-Pulmonary Institute (CPI), German Center for Lung Research (DZL), Justus-Liebig University, 35392 Giessen, Germany
Interests: cardiac hypertrophy; heart failure; cardiomyocyte cell cycle; cardiac fibrosis; pulmonary hypertension; pulmonary vascular biology; endothelial cell; endothelial dysfunction; animal models; signal transduction; receptor
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Universities of Giessen and Marburg Lung Center (UGMLC), Excellence Cluster Cardio-Pulmonary Institute (CPI), Member of the German Center for Lung Research (DZL), Justus Liebig University of Giessen, 35392 Giessen, Germany
Interests: pulmonary hypertension; right ventricular hypertrophy; high altitude medicine and physiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pulmonary hypertension (PH) comprises a group of severe clinical disorders, including pulmonary arterial hypertension (PAH), classified according to the World Health Organization (WHO) as Group 1 of PH. PAH is a chronic, progressive, and incurable disease of multifactorial pathobiology. PAH is characterized by vasoconstriction of the pulmonary vessels, an increase in pulmonary vascular resistance, and vascular tone. The remodeling in PAH is associated with endothelial cell dysfunction and intimal thickening, enhanced proliferation and a reduction in apoptosis of pulmonary smooth muscle cells, loss of pre-capillary arteries, perivascular inflammation, an increase in extracellular matrix deposition, and adventitial fibrosis. All of these processes cumulatively contribute to the progressive obliteration of the precapillary vessels, leading to an increase in pulmonary arterial pressure, right ventricular hypertrophy (RV), dysfunction, and death. The RV is the major determinant of functional state and prognosis in PAH. Plentiful molecular mechanisms contribute to the development of PAH and RV failure, including, in particular, an imbalance of vasoactive mediators, increased secretion of cytokines and chemokines, modulation of the activity of various growth factors, mitochondrial dysfunction, and changes in membrane receptors and ion channels. This Special Issue focuses on molecular mechanisms in PAH and RV hypertrophy and failure. We cordially welcome submissions, including original papers and reviews, on this broad topic.

Dr. Tatyana Novoyatleva
Dr. Akylbek Sydykov
Guest Editors

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Keywords

  • pulmonary hypertension
  • right ventricular hypertrophy
  • right heart failure
  • pulmonary arterial hypertension
  • pulmonary vascular cells
  • endothelial dysfunction
  • adventitial fibrosis

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Published Papers (1 paper)

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Research

14 pages, 4697 KiB  
Article
Intrapulmonary T Cells Are Sufficient for Schistosoma-Induced Pulmonary Hypertension
by Dara C. Fonseca Balladares, Biruk Kassa, Claudia Mickael, Rahul Kumar, Kevin Nolan, Thais C. F. Menezes, Michael H. Lee, Anthony M. Lau-Xiao, Ari B. Molofsky, Elina Wells and Brian B. Graham
Int. J. Mol. Sci. 2024, 25(17), 9202; https://doi.org/10.3390/ijms25179202 - 24 Aug 2024
Viewed by 964
Abstract
Background: Schistosomiasis is a parasitic infection that can cause pulmonary hypertension (PH). Th2 CD4 T cells are necessary for experimental Schistosoma-PH. However, if T cells migrate to the lung to initiate, the localized inflammation that drives vascular remodeling and PH is unknown. [...] Read more.
Background: Schistosomiasis is a parasitic infection that can cause pulmonary hypertension (PH). Th2 CD4 T cells are necessary for experimental Schistosoma-PH. However, if T cells migrate to the lung to initiate, the localized inflammation that drives vascular remodeling and PH is unknown. Methods: Mice were sensitized to Schistosoma mansoni eggs intraperitoneally and then challenged using tail vein injection. FTY720 was administered, which blocks lymphocyte egress from lymph nodes. T cells were quantified using flow cytometry, PH severity via heart catheterization, and cytokine concentration through ELISA. Results: FTY720 decreased T cells in the peripheral blood, and increased T cells in the mediastinal lymph nodes. However, FTY720 treatment resulted in no change in PH or type 2 inflammation severity in mice sensitized and challenged with S. mansoni eggs, and the number of memory and effector CD4 T cells in the lung parenchyma was also unchanged. Notably, intraperitoneal Schistosoma egg sensitization alone resulted in a significant increase in intravascular lymphocytes and T cells, including memory T cells, although there was no significant change in parenchymal cell density, IL-4 or IL-13 expression, or PH. Conclusion: Blocking T cell migration did not suppress PH following Schistosoma egg challenge. Memory CD4 T cells, located in the lung intravascular space following egg sensitization, appear sufficient to cause type 2 inflammation and PH. Full article
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