Heated vegetable oils and cardiovascular disease risk factors

Vascular Pharmacology, Год журнала: 2014, Номер 61(1), С. 1 - 9

Опубликована: Март 14, 2014

Язык: Английский

---

Reactive oxygen species induced Ca²⁺influx via TRPV4 and microvascular endothelial dysfunction in the SU5416/hypoxia model of pulmonary arterial hypertension

AJP Lung Cellular and Molecular Physiology, Год журнала: 2018, Номер 314(5), С. L893 - L907

Опубликована: Фев. 1, 2018

Pulmonary arterial hypertension (PAH) is a lethal disease characterized by elevations in pulmonary pressure, part due to formation of occlusive lesions the distal arterioles lung. These complex may comprise multiple cell types, including endothelial cells (ECs). To better understand molecular mechanisms underlying EC dysfunction PAH, lung microvascular (MVECs) were isolated from normoxic rats (N-MVECs) and subjected SU5416 plus hypoxia (SuHx), an experimental model PAH. Compared with N-MVECs, MVECs SuHx (SuHx-MVECs) appeared larger more spindle shaped morphologically expressed canonical smooth muscle markers muscle-specific α-actin myosin heavy chain addition such as Griffonia simplicifolia von Willebrand factor. SuHx-MVEC mitochondria dysfunctional, evidenced increased fragmentation/fission, decreased oxidative phosphorylation, reactive oxygen species (ROS) production. Functionally, SuHx-MVECs exhibited basal levels intracellular calcium concentration ([Ca2+]i) enhanced migratory proliferative capacity. Treatment global (TEMPOL) or mitochondria-specific (MitoQ) antioxidants ROS [Ca2]i SuHx-MVECs. TEMPOL MitoQ also migration proliferation Additionally, inhibition ROS-induced Ca2+ entry via pharmacologic blockade transient receptor potential vanilloid-4 (TRPV4) attenuated [Ca2]i, migration, proliferation. findings suggest role for mitochondrial influx TRPV4 promoting abnormal this PAH model.

Язык: Английский

---

Leukotriene B ₄ Activates Pulmonary Artery Adventitial Fibroblasts in Pulmonary Hypertension

Hypertension, Год журнала: 2015, Номер 66(6), С. 1227 - 1239

Опубликована: Окт. 6, 2015

A recent study demonstrated a significant role for leukotriene B4 (LTB4) causing pulmonary vascular remodeling in arterial hypertension. LTB4 was found to directly injure luminal endothelial cells and promote growth of the smooth muscle cell layer arterioles. The purpose this determine effects on adventitial layer, largely composed fibroblasts. Here, we demonstrate that enhanced human artery fibroblast proliferation, migration, differentiation dose-dependent manner through its cognate G-protein-coupled receptor, BLT1. activated by upregulating p38 mitogen-activated protein kinase as well Nox4-signaling pathways. In an autoimmune model hypertension, inhibition these pathways blocked perivascular inflammation, decreased Nox4 expression, reduced reactive oxygen species production, reversed arteriolar activation, attenuated hypertension development. This uncovers novel mechanism which further promotes pathogenesis, beyond established cells, activating

Язык: Английский

---

Galangin attenuates airway remodelling by inhibiting TGF-β1-mediated ROS generation and MAPK/Akt phosphorylation in asthma

Scientific Reports, Год журнала: 2015, Номер 5(1)

Опубликована: Июль 9, 2015

Abstract Galangin, a natural flavonol, has attracted much attention for its potential anti-inflammatory properties. However, role in the regulation of airway remodelling asthma not been explored. The present study aimed to elucidate effects galangin on chronic inflammation and investigate underlying mechanisms both vivo vitro . Ovalbumin (OVA)-sensitised mice were administered with 30 min before challenge. Our results showed that severe inflammatory responses occurred OVA-induced mice. Treatment markedly attenuated leakage cells into bronchoalveolar lavage fluid (BALF) decreased level OVA-specific IgE serum. Galangin significantly inhibited goblet cell hyperplasia, collagen deposition α-SMA expression. Lowered TGF-β1 suppressed expression VEGF MMP-9 observed BALF or lung tissue, implying an optimal anti-remodelling effect Consistently, TGF-β1-induced proliferation smooth muscle was reduced by , which might be due alleviation ROS levels inhibition MAPK pathway. Taken together, findings highlight novel as promising agent asthma, likely involves TGF-β1-ROS-MAPK

Язык: Английский

---

Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol

International Journal of Biological Sciences, Год журнала: 2017, Номер 13(8), С. 1067 - 1081

Опубликована: Янв. 1, 2017

The endothelial-to-mesenchymal transition (EndMT) has been demonstrated to be involved in pulmonary vascular remodeling.It is partly attributed oxidative and inflammatory stresses endothelial cells.In current study, we conducted a series of experiments clarify the effect salvianolic acid A (SAA), kind polyphenol compound, process EndMT human arterial cells vivo therapeutic efficacy on remodeling monocrotaline (MCT)-induced EndMT.EndMT was induced by TGFβ1 (HPAECs).SAA significantly attenuated EndMT, simultaneously inhibited cell migration reactive oxygen species (ROS) formation.In MCT-induced hypertension (PAH) model, SAA improved function, decreased level inflammation.Mechanistically, stimulated Nrf2 translocation subsequent heme oxygenase-1 (HO-1) up-regulation.The vitro abolished ZnPP, HO-1 inhibitor.In conclusion, this study indicates deleterious impact stress EndMT.Polyphenol antioxidant treatment may provide an adjunctive action alleviate via inhibiting EndMT.

Язык: Английский

---

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

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(9), С. 4980 - 4980

Опубликована: Май 7, 2021

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

Язык: Английский

---

Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and Ca²⁺ signaling

Physiological Reviews, Год журнала: 2022, Номер 103(3), С. 1827 - 1897

Опубликована: Ноя. 24, 2022

The pulmonary circulation is a low-resistance, low-pressure, and high-compliance system that allows the lungs to receive entire cardiac output. Pulmonary arterial pressure function of output vascular resistance, resistance inversely proportional fourth power intraluminal radius artery. Therefore, very small decrease lumen diameter results in significant increase pressure. hypertension fatal progressive disease with poor prognosis. Regardless initial pathogenic triggers, sustained vasoconstriction, concentric remodeling, occlusive intimal lesions, situ thrombosis, wall stiffening are major direct causes for elevated patients other forms precapillary hypertension. In this review, we aim discuss basic principles physiological mechanisms involved regulation lung hemodynamics function, changes vasculature contribute increased pressure, development progression We focus on reviewing roles membrane receptors, ion channels, intracellular Ca

Язык: Английский

---

Inflammation and immunity in the pathogenesis of hypoxic pulmonary hypertension

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Май 5, 2023

Hypoxic pulmonary hypertension (HPH) is a complicated vascular disorder characterized by diverse mechanisms that lead to elevated blood pressure in circulation. Recent evidence indicates HPH not simply pathological syndrome but instead complex lesion of cellular metabolism, inflammation, and proliferation driven the reprogramming gene expression patterns. One key underlying hypoxia, which drives immune/inflammation mediate homeostasis collaboratively controls remodeling lungs. This caused prolonged infiltration immune cells an increase several pro-inflammatory factors, ultimately leads dysregulation. Hypoxia has been associated with metabolic reprogramming, immunological dysregulation, adverse preclinical studies. Many animal models have developed mimic HPH; however, many them do accurately represent human disease state may be suitable for testing new therapeutic strategies. The scientific understanding rapidly evolving, recent efforts focused on interplay among metabolism development this disease. Through continued research more sophisticated models, it hoped we will able gain deeper implement effective therapies debilitating

Язык: Английский

---

Role of oxidative stress, inflammation, nitric oxide and transforming growth factor-beta in the protective effect of diosgenin in monocrotaline-induced pulmonary hypertension in rats

European Journal of Pharmacology, Год журнала: 2014, Номер 740, С. 379 - 387

Опубликована: Июль 22, 2014

Язык: Английский

---

Oxidative stress and nitric oxide signaling related biomarkers in patients with pulmonary hypertension: a case control study

BMC Pulmonary Medicine, Год журнала: 2015, Номер 15(1)

Опубликована: Май 1, 2015

Oxidative stress (OS) and reduced nitric oxide (NO) bioavailability contribute to the pathogenesis of pulmonary hypertension (PH). Whether there are associations between OS NO signaling biomarkers whether these associated with severity PH remain unclear. Blood samples were collected from 35 healthy controls patients arterial (PAH, n = 12) or chronic thromboembolic (CTEPH, 23). The mean artery pressure (mPAP) vascular resistance index (PVRI) measured by right heart catheterization. We derivative reactive oxygen molecules (d-ROMs), biological antioxidant potential (BAP) superoxide dismutase (SOD) automatic biochemical analyzer, malondialdehyde (MDA) asymmetric dimethylarginine (ADMA) enzyme-linked immunosorbent assay. relationship oxidative-antioxidative ADMA, as well their association hemodynamics, analyzed. Compared age- gender-matched controls, was no significant difference d-ROMs in PAH CTEPH patients; MDA increased (P 0.034); BAP SOD decreased 0.014, P < 0.001) 0.015, 0.001); ADMA level significantly higher 0.007) 0.001). No found. Serum concentration correlated mPAP (r 0.762, 0.006) PVRI 0.603, 0.038) patients. antioxidative impaired CTEPH. Increased serum is unfavorable hemodynamics Thus, may be useful evaluation risk stratification PAH.

Язык: Английский

---