Effects of the nerve growth factor and its carrier protein on the inflammatory response from human monocytes.

Background: The nerve growth factor (NGF) has been previously shown to be involved in cellular proliferation, differentiation, survival, or wound healing. This factor displays a variety of biological effects that yet remain to be explored. Previous data on cell lines show a pro-inflammatory role of NGF on monocytes.

NGF increases Connexin-43 expression and function in pulmonary arterial smooth muscle cells to induce pulmonary artery hyperreactivity.

Aims: Pulmonary hypertension (PH) is characterised by an increase in pulmonary arterial pressure, ultimately leading to right ventricular failure and death. We have previously shown that nerve growth factor (NGF) plays a critical role in PH. Our objectives here were to determine whether NGF controls Connexin-43 (Cx43) expression and function in the pulmonary arterial smooth muscle, and whether this mechanism contributes to NGF-induced pulmonary artery hyperreactivity.

[Nerve growth factor (NGF) in pulmonary hypertension (PH)].

Pulmonary hypertension (PH) is the main pathology in lung circulation, characterized by increased pressure in pulmonary arteries and ultimately resulting in right heart failure with potentially fatal outcomes. Given the current lack of available curative treatments, it is of paramount importance to identify novel therapeutic targets. Due to its involvement in pulmonary arterial remodeling, hyperreactivity, and inflammation, our explorations have focused on the nerve growth factor (NGF), offering promising avenues for innovative therapeutic approaches.

OP2113, a new drug for chronic hypoxia-induced pulmonary hypertension treatment in rat.

Background And Purpose: Pulmonary hypertension (PH) is a cardiovascular disease characterised by an increase in pulmonary arterial (PA) resistance leading to right ventricular (RV) failure. Reactive oxygen species (ROS) play a major role in PH. OP2113 is a drug with beneficial effects on cardiac injuries that targets mitochondrial ROS.

Inflammation and Oxidative Stress Induce NGF Secretion by Pulmonary Arterial Cells through a TGF-β1-Dependent Mechanism.

Expression of the nerve growth factor NGF is increased in pulmonary hypertension (PH). We have here studied whether oxidative stress and inflammation, two pathological conditions associated with transforming growth factor-β1 (TGF-β1) in PH, may trigger NGF secretion by pulmonary arterial (PA) cells. Effects of hydrogen peroxide (HO) and interleukin-1β (IL-1β) were investigated ex vivo on rat pulmonary arteries, as well as in vitro on human PA smooth muscle (hPASMC) or endothelial cells (hPAEC).

Piezo1 Channel Activation Reverses Pulmonary Artery Vasoconstriction in an Early Rat Model of Pulmonary Hypertension: The Role of Ca Influx and Akt-eNOS Pathway.

In intrapulmonary arteries (IPAs), mechanical forces due to blood flow control vessel tone, and these forces change during pulmonary hypertension (PH). Piezo1, a stretch-activated calcium channel, is a sensor of mechanical stress present in both endothelial cells (ECs) and smooth muscle cells (SMCs). The present study investigated the role of Piezo1 on IPA in the chronic hypoxia model of PH.

NiONP-Induced Oxidative Stress and Mitochondrial Impairment in an In Vitro Pulmonary Vascular Cell Model Mimicking Endothelial Dysfunction.

The development and use of nanomaterials, especially of nickel oxide nanoparticles (NiONPs), is expected to provide many benefits but also has raised concerns about the potential human health risks. Inhaled NPs are known to exert deleterious cardiovascular side effects, including pulmonary hypertension. Consequently, patients with pulmonary hypertension (PH) could be at increased risk for morbidity.

[Involvement of the Piezo1 and TRPV4 stretch-activated channels in pulmonary hypertension].

Pulmonary hypertension is a pulmonary circulation pathology characterized by remodelling and hyperreactivity of the pulmonary arteries. Vasodilatation/vasoconstriction balance is modified in favour of constriction via, among other things, the proliferation of smooth muscle cells and the development of endothelial dysfunction. In addition, the pulmonary arteries undergo modification of mechanical forces, inducing modified activation of stretch-activated channels (SAC) such as Piezo1 and TRPV4.

NiONPs-induced alteration in calcium signaling and mitochondrial function in pulmonary artery endothelial cells involves oxidative stress and TRPV4 channels disruption.

In New Caledonia, anthropic activities, such as mining, increase the natural erosion of soils in nickel mines, which in turn, releases nickel oxide nanoparticles (NiONPs) into the atmosphere. Pulmonary vascular endothelial cells represent one of the primary targets for inhaled nanoparticles. The objective of this study was to assess the cytotoxic effects of NiONPs on human pulmonary artery endothelial cells (HPAEC).

Mechanosensitivity in Pulmonary Circulation: Pathophysiological Relevance of Stretch-Activated Channels in Pulmonary Hypertension.

A variety of cell types in pulmonary arteries (endothelial cells, fibroblasts, and smooth muscle cells) are continuously exposed to mechanical stimulations such as shear stress and pulsatile blood pressure, which are altered under conditions of pulmonary hypertension (PH). Most functions of such vascular cells (e.g.

Effects of FW2 Nanoparticles Toxicity in a New In Vitro Pulmonary Vascular Cells Model Mimicking Endothelial Dysfunction.

Several epidemiological studies have revealed the involvement of nanoparticles (NPs) in respiratory and cardiovascular mortality. In this work, the focus will be on the effect of manufactured carbon black NPs for risk assessment of consumers and workers, as human exposure is likely to increase. Since the pulmonary circulation could be one of the primary targets of inhaled NPs, patients suffering from pulmonary hypertension (PH) could be a population at risk.

[The expression and role of nerve growth factor (NGF) in pulmonary hypertension].

Pulmonary hypertension is a severe multifactorial disease of the pulmonary circulation characterized by a progressive elevation in mean pulmonary arterial pressure (PAPm), leading to right ventricular failure and the death of the patient. Current therapies slow the progression of the disease but do not offer a cure. Nerve growth factor NGF is a growth factor playing a significant role in the pathophysiology of pulmonary hypertension, particularly in pulmonary arterial hyperreactivity, and the remodelling and inflammation of the pulmonary vasculature.

Connexin-43 is a promising target for pulmonary hypertension due to hypoxaemic lung disease.

The mechanisms underlying pulmonary hypertension (PH) are complex and multifactorial, and involve different cell types that are interconnected through gap junctional channels. Although connexin (Cx)-43 is the most abundant gap junction protein in the heart and lungs, and critically governs intercellular signalling communication, its contribution to PH remains unknown. The focus of the present study is thus to evaluate Cx43 as a potential new target in PH.

Altered vasoreactivity in neonatal rats with pulmonary hypertension associated with bronchopulmonary dysplasia: Implication of both eNOS phosphorylation and calcium signaling.

Bronchopulmonary dysplasia (BPD) consists of an arrest of pulmonary vascular and alveolar growth, with persistent hypoplasia of the pulmonary microvasculature and alveolar simplification. In 25 to 40% of the cases, BPD is complicated by pulmonary hypertension (BPD-PH) that significantly increases the risk of morbidity. In vivo studies suggest that increased pulmonary vascular tone could contribute to late PH in BPD.

Calcium signalling induced by in vitro exposure to silicium dioxide nanoparticles in rat pulmonary artery smooth muscle cells.

The development and use of nanomaterials, especially engineered nanoparticles (NP), is expected to provide many benefits. But at the same time the development of such materials is also feared because of their potential human health risks. Indeed, NP display some characteristics similar to ultrafine environmental particles which are known to exert deleterious cardiovascular effects including pro-hypertensive ones.

CT evaluation of small pulmonary vessels area in patients with COPD with severe pulmonary hypertension.

Rationale: Severe pulmonary hypertension (PH) is very uncommon in COPD, and a distinct phenotype has been hypothesised. We aimed to evaluate whether CT can help to recognise this condition non-invasively by measuring small pulmonary vessels.

Material And Methods: Patients with COPD who underwent pulmonary function tests, unenhanced CT of the chest and right heart catheterisation (RHC) during a period of stability were included in the study.

Involvement of Heme Oxygenase-1 in particulate matter-induced impairment of NO-dependent relaxation in rat intralobar pulmonary arteries.

Particulate air pollution exerts deleterious effects on cardiovascular system. We previously described that exposure to urban particulate matter (SRM1648) impairs nitric oxide (NO, a major vasculoprotective factor) responsiveness in intrapulmonary arteries. As Heme Oxygenase-1 (HO-1) is induced by urban particles in some cell types and is known to alter NO-dependent signaling pathway, the objective was to characterize HO-1 involvement in SRM1648-induced impairment of NO-dependent relaxation in intrapulmonary arteries.

Role of Nerve Growth Factor in Development and Persistence of Experimental Pulmonary Hypertension.

Rationale: Pulmonary hypertension (PH) is characterized by a progressive elevation in mean pulmonary arterial pressure, often leading to right ventricular failure and death. Growth factors play significant roles in the pathogenesis of PH, and their targeting may therefore offer novel therapeutic strategies in this disease.

Objectives: To evaluate the nerve growth factor (NGF) as a potential new target in PH.

Mitochondria: roles in pulmonary hypertension.

Mitochondria are essential cell organelles responsible for ATP production in the presence of oxygen. In the pulmonary vasculature, mitochondria contribute to physiological intracellular signalling pathways through production of reactive oxygen species and play the role of oxygen sensors that coordinate hypoxic pulmonary vasoconstriction. Mitochondria also play a pathophysiological role in pulmonary hypertension (PH).

Biopterin metabolism and eNOS expression during hypoxic pulmonary hypertension in mice.

Tetrahydrobiopterin (BH4), which fosters the formation of and stabilizes endothelial NO synthase (eNOS) as an active dimer, tightly regulates eNOS coupling / uncoupling. Moreover, studies conducted in genetically-modified models demonstrate that BH4 pulmonary deficiency is a key determinant in the pathogenesis of pulmonary hypertension. The present study thus investigates biopterin metabolism and eNOS expression, as well as the effect of sepiapterin (a precursor of BH4) and eNOS gene deletion, in a mice model of hypoxic pulmonary hypertension.

Reactive oxygen species as therapeutic targets in pulmonary hypertension.

Pulmonary hypertension (PH) is characterized by a progressive elevation of pulmonary arterial pressure due to alterations of both pulmonary vascular structure and function. This disease is rare but life-threatening, leading to the development of right heart failure. Current PH treatments, designed to target altered pulmonary vascular reactivity, include vasodilating prostanoids, phosphodiesterase-5 inhibitors and endothelin-1 receptor antagonists.