Involvement of S100A4/Mts1 and associated proteins in the protective effect of fluoxetine against MCT - Induced pulmonary hypertension in rats.

Background: Pulmonary arterial hypertension (PAH) is a complex pulmonary vasculature disease characterized by remodeling of the pulmonary vessels and a persistent increase in the pulmonary vascular resistance (PVR) with a poor prognosis. Serotonin increases the expression of S100A4/Mts1, which in turn stimulates the proliferation and migration of human pulmonary artery smooth muscle cells through the interaction with RAGE (receptor for advanced glycation end products) and thus S100A4/Mts1 has been implicated in the development of PAH in vitro. Fluoxetine, a selective serotonin re-uptake inhibitor has been shown to protect against PAH.

Role of Noncoding RNA in Pulmonary Arterial Hypertension and Potential Drug Therapeutic Target.

Pulmonary arterial hypertension (PAH) is a devastating disease without effective drugs available for its treatment. An in-depth exploration of the pathogenesis of PAH, as well as inquiry into potential therapeutic targets, remains an urgent issue. Non-coding RNAs (ncRNAs) have arisen as key players in malignant tumors, cardiovascular diseases and more recently in PAH progression and development.

PCPA protects against monocrotaline-induced pulmonary arterial remodeling in rats: potential roles of connective tissue growth factor.

The purpose of this study was to investigate the mechanism of monocrotaline (MCT)-induced pulmonary artery hypertension (PAH) and determine whether 4-chloro-DL-phenylalanine (PCPA) could inhibit pulmonary arterial remodeling associated with connective tissue growth factor (CTGF) expression and downstream signal pathway. MCT was administered to forty Sprague Dawley rats to establish the PAH model. PCPA was administered at doses of 50 and 100 mg/kg once daily for 3 weeks via intraperitoneal injection.

The protective effects of PCPA against monocrotaline-induced pulmonary arterial hypertension are mediated through the downregulation of NFAT-1 and NF-κB.

Inflammation and remodeling play a role in the pathogenesis of pulmonary arterial hypertension (PAH). Nuclear factor-κB (NF-κB) and nuclear factor of activated T cells-1 (NFAT-1) participate in inflammation and remodeling in a number of diseases. As a tryptophan hydroxylase inhibitor, 4-chloro-DL-phenylalanine (PCPA) had been reported to exert anti-inflammatory and remodeling effects.

Suppression of nuclear factor erythroid‑2‑related factor 2‑mediated antioxidative defense in the lung injury induced by chronic exposure to methamphetamine in rats.

The imbalance between oxidative stress and antioxidant defense is important in the pathogenesis of lung diseases. Nuclear factor erythroid‑2‑related factor 2 (Nrf2) is a key transcriptional factor that regulates the antioxidant response. The purpose of the present study was to investigate whether Nrf2‑mediated antioxidative defense is involved in methamphetamine (MA)‑induced lung injury in rats.

TBHQ Alleviated Endoplasmic Reticulum Stress-Apoptosis and Oxidative Stress by PERK-Nrf2 Crosstalk in Methamphetamine-Induced Chronic Pulmonary Toxicity.

Methamphetamine (MA) leads to cardiac and pulmonary toxicity expressed as increases in inflammatory responses and oxidative stress. However, some interactions may exist between oxidative stress and endoplasmic reticulum stress (ERS). The current study is designed to investigate if both oxidative stress and ERS are involved in MA-induced chronic pulmonary toxicity and if antioxidant tertiary butylhydroquinone (TBHQ) alleviated ERS-apoptosis and oxidative stress by PERK-Nrf2 crosstalk.

Endoplasmic reticulum stress and apoptosis via PERK-eIF2α-CHOP signaling in the methamphetamine-induced chronic pulmonary injury.

Methamphetamine (MA) leads to multiple organs lesions and apoptosis. The aim of this study is to investigate if endoplasmic reticulum stress (ERS) - initiated apoptosis is involved in the chronic pulmonary injury induced by MA. In this study, rats were divided into a control group, methamphetamine 5mg/kg group and methamphetamine 10mg/kg group.

Fluoxetine protects against methamphetamine‑induced lung inflammation by suppressing oxidative stress through the SERT/p38 MAPK/Nrf2 pathway in rats.

Methamphetamine (MA) abuse is a major public health and safety concern throughout the world and a growing burden on healthcare costs. The purpose of the present study was to investigate the protective effect of fluoxetine against MA‑induced chronic pulmonary inflammation and to evaluate the potential role of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidative stress. Wistar rats were divided into control, MA and two fluoxetine‑treated groups.

[Clinical outcome of arthroscopic excision of the os subfibulare in ankle pain].

Objective: To evaluate the clinical effect of arthroscopic excision of the os subfibulare in anterior-lateral ankle pain.

Methods: From December 2005 to Augest 2014, 16 patients suffering from pain associated with an os subfibulare in the anterior-lateral side of their ankles were reviewed. Among the patients,11 patients were male and 5 were female, with a mean age of (33.

4-Chloro-DL-phenylalanine protects against monocrotaline‑induced pulmonary vascular remodeling and lung inflammation.

The present study was performed to investigate the effects of 4-chloro-DL-phenylalanine (PCPA), a tryptophan hydroxylase (Tph) inhibitor (TphI), on pulmonary vascular remodeling and lung inflammation in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. Animal models of PAH were established using Sprague-Dawley (SD) rats by a single intraperitoneal injection of MCT (60 mg/kg). PCPA (50 or 100 mg/kg/day) was administered to the rats with PAH.

Fluoxetine inhibits monocrotaline-induced pulmonary arterial remodeling involved in inhibition of RhoA-Rho kinase and Akt signalling pathways in rats.

Activation of the small GTPase Ras homolog gene family member A (RhoA) and Rho-associated kinase (ROCK) are important in the pathogenesis of pulmonary arterial hypertension (PAH). Selective serotonin reuptake inhibitors inhibit activation of RhoA and ROCK in vitro, and ameliorate PAH and pulmonary arterial remodeling in vivo. However, little is known about whether the RhoA-ROCK signalling pathway is involved in the treatment of PAH with fluoxetine in vivo.

Fluoxetine attenuates chronic methamphetamine-induced pulmonary arterial remodelling: possible involvement of serotonin transporter and serotonin 1B receptor.

Epidemiological data have shown that methamphetamine (MA) abuse significantly increases the risk of developing pulmonary arterial hypertension (PAH). To investigate whether MA could induce PAH and its possible mechanism, rats were exposed daily to MA for 5 weeks in the absence or presence of fluoxetine. The results showed that the pulmonary arterial pressure was not significantly increased, but the pulmonary arterial remodelling was markedly developed in the MA exposure group.

Fluoxetine protects against monocrotaline-induced pulmonary arterial remodeling by inhibition of hypoxia-inducible factor-1α and vascular endothelial growth factor.

The selective serotonin re-uptake inhibitor fluoxetine has been shown to protect against monocrotaline (MCT)-induced pulmonary hypertension in rats. To investigate the possible role of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in mediating this protective effect, MCT-treated rats were administered fluoxetine by gavage, at doses of 2 mg/kg body mass or 10 mg/kg once daily for 3 weeks. Changes in pulmonary hemodynamic parameters, pulmonary artery morphologies, and expressions of HIF-1α and VEGF were assessed.

Involvement of BMPR2 in the protective effect of fluoxetine against monocrotaline-induced endothelial apoptosis in rats.

Mutations in bone morphogenetic protein (BMP) receptor II (BMPR2) are associated with the apoptosis of the pulmonary artery endothelial cells and the loss of the pulmonary small vessels. The present study was designed to investigate the involvement of BMPR2 in the protective effect of fluoxetine against monocrotaline (MCT)-induced endothelial apoptosis in rats. Models of pulmonary arterial hypertension in rats were established by a single intraperitoneal injection of MCT (60 mg/kg).

Downregulation of osteopontin is associated with fluoxetine amelioration of monocrotaline-induced pulmonary inflammation and vascular remodelling.

1. Osteopontin (OPN) has emerged as a key factor in inflammatory activation and cardiovascular remodelling. The aim of the present study was to investigate the involvement of OPN in fluoxetine amelioration of monocrotaline (MCT)-induced pulmonary inflammation and vascular remodelling in rats.

Fluoxetine inhibited extracellular matrix of pulmonary artery and inflammation of lungs in monocrotaline-treated rats.

Aim: To investigate the effects of the selective serotonin reuptake inhibitor (SSRI) fluoxetine on extracellular matrix (ECM) remodeling of the pulmonary artery and inflammation of the lungs in pulmonary arterial hypertension (PAH) induced by monocrotaline in rats.

Methods: MCT-induced chronic PAH was established in Wistar rats. After treatment with fluoxetine for 3 weeks, pulmonary hemodynamic measurement and morphological investigation of lung tissues were undertaken.

Fluoxetine protects against monocrotaline-induced pulmonary arterial hypertension: potential roles of induction of apoptosis and upregulation of Kv1.5 channels in rats.

1. Suppressing apoptosis and downregulating K(+) channels in pulmonary artery smooth muscle cells (PASMC) have been implicated in the development of pulmonary vascular medial hypertrophy and pulmonary arterial hypertension (PAH). Previous studies have shown that selective serotonin re-uptake inhibitors (SSRIs) protected against PAH.

[Changes of pulmonary artery protein kinase C activity in rats with chronic inflammatory pulmonary hypertension].

Objective: To observe the changes in pulmonary artery protein kinase C (PKC) activity in rats with chronic inflammatory pulmonary hypertension (PHT).

Methods: Chronic inflammatory PHT was induced in rats with monocrotaline. The PKC activities in the rat pulmonary arteries were measured by radioactive assay during the development of PHT.

Sertraline protects against monocrotaline-induced pulmonary hypertension in rats.

1. Serotonin (5-HT), as a type of mitogen for smooth muscle cells, plays an important role in the development of pulmonary hypertension. It is known that selective serotonin re-uptake inhibitors (SSRI) inhibit 5-HT internalization.

Antagonism of transforming growth factor-Beta signaling inhibits fibrosis-related genes.

In the fibrotic process, the transforming growth factor-beta1 (TGF-beta1)/Smad3 (Sma- and Mad-related protein 3) signaling plays a central role. To screen for antagonists of TGF-beta1/Smad3 signaling and to investigate their effects on the genes related to fibrosis, we construct a molecular model with a luciferase reporter gene. Results showed that both SB-431542 [4-(5-benzo[1,3]dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)-benzamide] and small interference RNA (siRNA) against Smad3 could dose-dependently suppress the reporter gene.

5-Hydroxytryptamine-induced proliferation of pulmonary artery smooth muscle cells are extracellular signal-regulated kinase pathway dependent.

Aim: To investigate the effect of 5-hydroxytryptamine transporter (5-HTT) inhibitor fluoxetine and antisense oligodeoxynucleotide (ODN) to extracelluar signal-regulated kinases (ERKs) on pulmonary arterial smooth muscle cells (PASMCs) proliferation induced by 5-HT.

Methods: Liposomal transfection was used to introduce ODNs to ERK1/2 into cultured rat PASMCs and the transfection efficiency was measured by observing the uptake of the fluorecein isothiocynate (FITC)-labeled antisense ODN in PASMCs. The effects of 5-HTT selective inhibitor fluoxetine and ODNs on the proliferation of PASMCs were evaluated by cell number counting and cell cycle analysis, and measured by microculture tetrazolium (MTT) assay and flow cytometry (FCM), respectively.

Vasodilatation produced by orientin and its mechanism study.

In this paper we investigated the vascular activity and possible mechanism of Orientin, from bamboo leaves (Phyllostachys nigra), in isolated thoracic aortic rings from New Zealand rabbit. Among the four compounds, studied, only Orientin relaxed phenylephrine-induced contractions with an IC50 value of 2.28 microM in the endothelium intact and with an IC50 value around 7.

The serotonin receptor and transporter as potential therapeutic targets for pulmonary hypertension.

Pulmonary hypertension (PHT) results from compromised pulmonary vasoconstriction and vascular remodeling. Serotonin (5-hydroxytryptamine/5-HT) is one of the important vasomotor agents, and its importance in the pathogenesis of PHT is currently being investigated. In most mammalian species, PHT can result from numerous serotonergic drugs, demonstrating that various 5-HT receptor subtypes and the 5-HT transporter (5-HTT) contribute to PHT.

Effects of dl-praeruptorin A on nucleus factor-kappaB and tumor necrosis factor-alpha expression in ischemia-reperfusion hearts.

Aim: To study the effects of dl-praeruptorin A (Pd-Ia) on nucleus factor-kappaB (NF-kappaB) activativity and tumor necrosis factor-alpha (TNF-alpha) expression in ischemia-reperfusion (I/R) myocardium.

Methods: Langendorff's isolated rat heart was subjected to a 10-min ischemia followed by a 30-min reperfusion. NF-kappaB activity in nucleus was analyzed by Sandwich Enzyme-Linked Immunosorbent Assay (ELISA).