Molecular Pathways in Pulmonary Arterial Hypertension

Shah, Aangi; Vorla, Mounica

doi:10.3390/ijms231710001

Cited by 26 publications

(24 citation statements)

References 133 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nitric oxide, prostanoid and endothelin are the three pathways currently used to treat patients with pulmonary hypertension [ 10 ]. Despite advances in the diagnosis and treatment of pulmonary hypertension, several conditions within the groups of pulmonary hypertension remain without approved therapies, one of which is COPD associated with pulmonary hypertension [ 1 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Increased Thromboxane A2 Levels in Pulmonary Artery Smooth Muscle Cells Isolated from Patients with Chronic Obstructive Pulmonary Disease

Alqarni

2023

Medicina

View full text Add to dashboard Cite

Introduction: Pulmonary hypertension due to chronic obstructive pulmonary disease (COPD) is classified as Group 3 pulmonary hypertension, with no current proven targeted therapies. It has been shown that cigarette smoke, the main risk factor for COPD, can increase thromboxane A2 production in healthy human pulmonary artery smooth muscle cells and pulmonary artery endothelial cells, and that blocking the effect of increased thromboxane A2 using daltroban, a thromboxane A2 receptor antagonist, can inhibit cigarette smoke-induced pulmonary artery cell proliferation. However, it is largely unknown whether thromboxane A2 is increased in smokers with COPD. Therefore, the aim of this study was to assess the level of thromboxane A2 production in patients with COPD who smoke. Methods: Pulmonary artery smooth muscle cells from three smokers with COPD and three healthy donors were cultured in cell culture medium. The culture medium was collected and the thromboxane B2 (a stable metabolite of thromboxane A2) released in the culture medium was quantified using an ELISA kit. The data were normalised with the total protein concentration and then expressed in pg/mg protein. Demographic data were collected and baseline pulmonary function tests of patients with COPD were conducted. Results: The mean age of patients with COPD was 69 ± 7 years. All patients were smokers and had a mean smoking history of 39.66 ± 9.50 packs per year. The mean forced expiratory volume in one second, that is, FEV1%, and the ratio of forced vital capacity (FVC) to FEV1% of COPD patients were 63.33 ± 19.60% and 52.66 ± 14.64%, respectively. The results revealed that thromboxane A2 production was significantly increased in pulmonary artery smooth muscle cells from smokers with COPD (434.56 ± 82.88 pg/mg protein) compared with the thromboxane A2 levels in pulmonary artery smooth muscle cells from healthy donors (160 ± 59.3 pg/mg protein). Conclusions: This is the first report of increased thromboxane A2 production in pulmonary artery smooth muscle cells from smokers with COPD. This observation strongly suggests that thromboxane A2 can be used as a novel therapeutic target for the treatment of patients with COPD-associated pulmonary hypertension.

show abstract

Section: Discussionmentioning

confidence: 99%

“…With prostaglandin I2, thromboxane A 2 plays a key role in regulating cardiovascular homeostasis. It induces pulmonary vasoconstriction, pulmonary artery cell proliferation and platelet aggregation [ 10 ]. An imbalance with increased thromboxane A 2 and reduced prostaglandin I2 is thought to contribute to pulmonary hypertension [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Increased Thromboxane A2 Levels in Pulmonary Artery Smooth Muscle Cells Isolated from Patients with Chronic Obstructive Pulmonary Disease

Alqarni

2023

Medicina

View full text Add to dashboard Cite

show abstract

“…The pathophysiology of PAH is complex and variable given the multiplicity of molecular mechanisms and the underlying disorders implicated in the pathogenesis. Intricate crosstalk among various signaling pathways involving nitric oxide, prostacyclin, serotonin along with neurohumoral and hormonal pathways, genetic predisposition with epigenetic modifications, mitochondria related metabolic milieu dysregulation, and environmental and inflammatory insults, all participate to form a complex endophenotype resulting in the pathological changes noted in PAH [ 10 ]. However, the most common pathological features, irrespective of the initial instigating injury, are pulmonary artery endothelial cell (PAEC) dysfunction, pulmonary artery smooth muscle cell (PASMC) proliferation and migration, and dysregulated fibroblast activity [ 11 ].…”

Section: Pathophysiology Of Pulmonary Arterial Hypertensionmentioning

confidence: 99%

New Drugs and Therapies in Pulmonary Arterial Hypertension

Shah

Beckmann

Vorla

2023

IJMS

Self Cite

View full text Add to dashboard Cite

Pulmonary arterial hypertension is a chronic, progressive disorder of the pulmonary vasculature with associated pulmonary and cardiac remodeling. PAH was a uniformly fatal disease until the late 1970s, but with the advent of targeted therapies, the life expectancy of patients with PAH has now considerably improved. Despite these advances, PAH inevitably remains a progressive disease with significant morbidity and mortality. Thus, there is still an unmet need for the development of new drugs and other interventional therapies for the treatment of PAH. One shortcoming of currently approved vasodilator therapies is that they do not target or reverse the underlying pathogenesis of the disease process itself. A large body of evidence has evolved in the past two decades clarifying the role of genetics, dysregulation of growth factors, inflammatory pathways, mitochondrial dysfunction, DNA damage, sex hormones, neurohormonal pathways, and iron deficiency in the pathogenesis of PAH. This review focuses on newer targets and drugs that modify these pathways as well as novel interventional therapies in PAH.

show abstract

“…The pathobiology of pulmonary vascular remodeling is characterized by PA endothelial cell (PAEC) dysfunction and apoptosis with the subsequent reactive proliferation of PA smooth muscle cells (PASMCs), increased extracellular matrix (ECM) deposition, and inflammatory/immune cell infiltration of the pulmonary vascular wall (1). Despite several decades of research in this field, disease development and progression mechanisms remain 10.3389/fcvm.2023.1118516 incompletely defined (6). Alterations of several signaling pathways have been shown to participate in the pathogenesis of pulmonary vascular remodeling.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic targeting of mineralocorticoid receptors in pulmonary hypertension: Insights from basic research

Mamazhakypov

Lother

2023

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling and associated with adverse outcomes. In patients with PH, plasma aldosterone levels are elevated, suggesting that aldosterone and its receptor, the mineralocorticoid receptor (MR), play an important role in the pathophysiology of PH. The MR plays a crucial role in adverse cardiac remodeling in left heart failure. A series of experimental studies from the past few years indicate that MR activation promotes adverse cellular processes that lead to pulmonary vascular remodeling, including endothelial cell apoptosis, smooth muscle cell (SMC) proliferation, pulmonary vascular fibrosis, and inflammation. Accordingly, in vivo studies have demonstrated that pharmacological inhibition or cell-specific deletion of the MR can prevent disease progression and partially reverse established PH phenotypes. In this review, we summarize recent advances in MR signaling in pulmonary vascular remodeling based on preclinical research and discuss the potential, but also the challenges, in bringing MR antagonists (MRAs) into clinical application.

show abstract

Molecular Pathways in Pulmonary Arterial Hypertension

Cited by 26 publications

References 133 publications

Increased Thromboxane A2 Levels in Pulmonary Artery Smooth Muscle Cells Isolated from Patients with Chronic Obstructive Pulmonary Disease

Increased Thromboxane A2 Levels in Pulmonary Artery Smooth Muscle Cells Isolated from Patients with Chronic Obstructive Pulmonary Disease

New Drugs and Therapies in Pulmonary Arterial Hypertension

Therapeutic targeting of mineralocorticoid receptors in pulmonary hypertension: Insights from basic research

Contact Info

Product

Resources

About