Dopamine D1 receptor activation ameliorates ox-LDL-induced endothelial cell senescence via CREB/Nrf2 pathway.

Endothelial cell senescence is involved in endothelial dysfunction and aging-related vascular diseases. The D1-like dopamine receptor (DR1), a number of G-protein-coupled receptors, is currently under consideration as a potential therapeutic target for the prevention of atherosclerosis. However, the role of DR1 in regulating ox-LDL-stimulated endothelial cell senescence remains unknown.

DR1 Activation Inhibits the Proliferation of Vascular Smooth Muscle Cells through Increasing Endogenous HS in Diabetes.

Tissue ischemia and hypoxia caused by the abnormal proliferation of smooth muscle cells (SMCs) in the diabetic state is an important pathological basis for diabetic microangiopathy. Studies in recent years have shown that the chronic complications of diabetes are related to the decrease of endogenous hydrogen sulfide (HS) in diabetic patients, and it has been proven that HS can inhibit the proliferation of vascular SMCs (VSMCs). Our study showed that the endogenous HS content and the expression of cystathionine gamma-lyase (CSE), which is the key enzyme of HS production, were decreased in arterial SMCs of diabetic mice.

Sodium hydrosulfide inhibiting endothelial cells injury and neutrophils activation via IL-8/CXCR2/ROS/NF-κB axis in type 1 diabetes mellitus rat.

Aims: Hydrogen sulfide (HS) prevents endothelial cells injury. However, the complicated mechanism of sodium hydrosulfide (NaHS, a donor that produces HS) which inhibits the endothelial cells injury which correlated the activation of neutrophil in the type 1 diabetes mellitus (T1DM) rats has not been previously investigated.

Methods And Results: In the experiment, the T1DM animal model was established, the IL-1β, IL-8 were determined by western blotting and ELISA, the expressions of the Bax and Bcl-2 of endothelial cells and the CXCR2, CSE, phosphor-IκBα and NF-kB of neutrophils were measured by western blotting.

DR1 activation promotes vascular smooth muscle cell apoptosis via up-regulation of CSE/H S pathway in diabetic mice.

The important role of hydrogen sulfide (H S) as a novel gasotransmitter in inhibiting proliferation and promoting apoptosis of vascular smooth muscle cells (VSMCs) has been widely recognized. The dopamine D1 receptor (DR1), a G protein coupled receptor, inhibits atherosclerosis by suppressing VSMC proliferation. However, whether DR1 contributes to VSMC apoptosis via the induction of endogenous H S in diabetic mice is unclear.

Exogenous hydrogen sulfide protects from endothelial cell damage, platelet activation, and neutrophils extracellular traps formation in hyperhomocysteinemia rats.

Hydrogen sulfide (HS) prevents endothelial cells damage and P-selectin of platelets promotes neutrophils extracellular traps (NETs) formation. However, how sodium hydrosulfide (NaHS), a donor that produces HS regulates the activation of platelets and whether HS inhibits the formation of neutrophils extracellular traps in hyperhomocysteinemia rats have not been previously investigated. The morphological and ultrastructural alterations of endothelial cells (ECs) and platelets were tested by transmission electron microscopy.

Spermine and spermidine reversed age-related cardiac deterioration in rats.

Aging is the most important risk factor for cardiovascular disease (CVD). Slowing or reversing the physiological impact of heart aging may reduce morbidity and mortality associated with age-related CVD. The polyamines, spermine (SP) and spermidine (SPD) are essential for cell growth, differentiation and apoptosis, and levels of both decline with age.

DR1 activation reduces the proliferation of vascular smooth muscle cells by JNK/c-Jun dependent increasing of Prx3.

Vascular smooth muscle cells (VSMCs) proliferation is a key process in atherosclerosis. However, little is known about the underlying mechanisms, leading to a lack of effective therapy. This study was to investigate whether dopamine receptor 1 (DR1) is involved in the VSMCs proliferation and related mechanisms.

Calcium sensing receptor initiating cystathionine-gamma-lyase/hydrogen sulfide pathway to inhibit platelet activation in hyperhomocysteinemia rat.

Hyperhomocysteinemia (HHcy, high homocysteine) induces the injury of endothelial cells (ECs). Hydrogen sulfide (HS) protects ECs and inhibits the activation of platelets. Calcium-sensing receptor (CaSR) regulates the production of endogenous HS.

Suppression of calcium‑sensing receptor ameliorates cardiac hypertrophy through inhibition of autophagy.

The calcium-sensing receptor (CaSR) releases intracellular calcium ([Ca2+]i) by accumulating inositol phosphate. Changes in [Ca2+]i initiate myocardial hypertrophy. Furthermore, autophagy associated with [Ca2+]i.

[Effects of activation of dopamine type I receptor on the produc-tion of NO/NOS in ox-LDL activated THP-1 cells].

Objective: To study the effect of excited dopamine type I receptor on the production of nitric oxide/nitric oxide synthase(NO/NOS)in ox-LDL activated THP-1 cells and the possible mechanism.

Methods: Cultured THP-1 cells activated by PMA were randomly assigned in the following groups:control group (control), oxidized low density lipoprotein group (ox-LDL), dopamine receptor 1(DR1) agonist group (SKF), DR1 antagonist group (SCH), ERK blocker group (PD98059). Oil Red O staining was used to identify the accumulation of cellular lipid.

Calhex₂₃₁ Ameliorates Cardiac Hypertrophy by Inhibiting Cellular Autophagy in Vivo and in Vitro.

Background/aims: Intracellular calcium concentration ([Ca2+]i) homeostasis, an initial factor of cardiac hypertrophy, is regulated by the calcium-sensing receptor (CaSR) and is associated with the formation of autolysosomes. The aim of this study was to investigate the role of Calhex231, a CaSR inhibitor, on the hypertrophic response via autophagy modulation.

Methods: Cardiac hypertrophy was induced by transverse aortic constriction (TAC) in 40 male Wistar rats, while 10 rats underwent a sham operation and served as controls.

[Effects and mechanisms of low concentration dopamine on hydrogen peroxide-induced apoptosis in cultured neonatal rat cardiomyocytes].

Objective: To study the effects of low concentration dopamine(DA) on hydrogen peroxide-induced apoptosis in cultured rat cardiomyocytes as well as the possible molecular mechanisms.

Methods: Cultured neonatal rat cardiomyocytes were randomly divided into the following groups: control group (control), hydrogen peroxide group (H2O2), pretreated with low concentration dopamine ( DA + H2O2), dopamine receptor l(DR1) antagonist group (DR1 + DA + H2O2), dopamine receptor 2(DR2) antagonist group (DR2 + DA + H2O2). The cell apoptosis was then assessed by MTT and flow cytometry.

The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages.

Purpose: To investigate the sonoactivity of hypericin (HY), together with its sonodynamic effect on THP-1 macrophages and the underlying mechanism.

Materials And Methods: CCK-8 was used to examine cell viability. Confocal laser scanning microscopy was performed to assess the localization of HY in cells, reactive oxygen species (ROS) generation, and opening of the mitochondrial permeability transition pore (mPTP) after different treatments.

Constitutive BDNF/TrkB signaling is required for normal cardiac contraction and relaxation.

BDNF and its associated tropomyosin-related kinase receptor B (TrkB) nurture vessels and nerves serving the heart. However, the direct effect of BDNF/TrkB signaling on the myocardium is poorly understood. Here we report that cardiac-specific TrkB knockout mice (TrkB(-/-)) display impaired cardiac contraction and relaxation, showing that BDNF/TrkB signaling acts constitutively to sustain in vivo myocardial performance.

Sodium hydrosulfide attenuates hyperhomocysteinemia rat myocardial injury through cardiac mitochondrial protection.

Hydrogen sulfide (H2S) plays an important role during rat myocardial injury. However, little is known about the role of H2S in hyperhomocysteinemia (HHcy)-induced cardiac dysfunction as well as the underlying mechanisms. In this study, we investigated whether sodium hydrosulfide (NaHS, a H2S donor) influences methionine-induced HHcy rat myocardial injury in intact rat hearts and primary neonatal rat cardiomyocytes.

Real-time detection of intracellular reactive oxygen species and mitochondrial membrane potential in THP-1 macrophages during ultrasonic irradiation for optimal sonodynamic therapy.

Reactive oxygen species (ROS) elevation and mitochondrial membrane potential (MMP) loss have been proven recently to be involved in sonodynamic therapy (SDT)-induced macrophage apoptosis and necrosis. This study aims to develop an experimental system to monitor intracellular ROS and MMP in real-time during ultrasonic irradiation in order to achieve optimal effect in SDT. Cultured THP-1 derived macrophages were incubated with 5-aminolevulinic acid (ALA), and then sonicated at different intensities.

Synthesis and chemical and biological comparison of nitroxyl- and nitric oxide-releasing diazeniumdiolate-based aspirin derivatives.

Structural modifications of nonsteroidal anti-inflammatory drugs (NSAIDs) have successfully reduced the side effect of gastrointestinal ulceration without affecting anti-inflammatory activity, but they may increase the risk of myocardial infarction with chronic use. The fact that nitroxyl (HNO) reduces platelet aggregation, preconditions against myocardial infarction, and enhances contractility led us to synthesize a diazeniumdiolate-based HNO-releasing aspirin and to compare it to an NO-releasing analogue. Here, the decomposition mechanisms are described for these compounds.

An animal model of atherosclerotic plaque disruption and thrombosis in rabbit using pharmacological triggering to plaques induced by perivascular collar placement.

Introduction: Limited availability of suitable animal model of plaque disruption and thrombosis has hampered the study of mechanism and preclinical evaluation of plaque-stabilizing therapies. This study aims to develop an animal model of atherosclerotic plaque disruption and thrombosis in rabbit femoral artery.

Methods: Silastic collars were placed around the bilateral femoral arteries of rabbits, which had been fed with atherogenic diet for 7 days.

GSH or palmitate preserves mitochondrial energetic/redox balance, preventing mechanical dysfunction in metabolically challenged myocytes/hearts from type 2 diabetic mice.

In type 2 diabetes, hyperglycemia and increased sympathetic drive may alter mitochondria energetic/redox properties, decreasing the organelle's functionality. These perturbations may prompt or sustain basal low-cardiac performance and limited exercise capacity. Yet the precise steps involved in this mitochondrial failure remain elusive.

Creatine kinase-mediated improvement of function in failing mouse hearts provides causal evidence the failing heart is energy starved.

ATP is required for normal cardiac contractile function, and it has long been hypothesized that reduced energy delivery contributes to the contractile dysfunction of heart failure (HF). Despite experimental and clinical HF data showing reduced metabolism through cardiac creatine kinase (CK), the major myocardial energy reserve and temporal ATP buffer, a causal relationship between reduced ATP-CK metabolism and contractile dysfunction in HF has never been demonstrated. Here, we generated mice conditionally overexpressing the myofibrillar isoform of CK (CK-M) to test the hypothesis that augmenting impaired CK-related energy metabolism improves contractile function in HF.

Thioredoxin reductase-2 is essential for keeping low levels of H(2)O(2) emission from isolated heart mitochondria.

Respiring mitochondria produce H(2)O(2) continuously. When production exceeds scavenging, H(2)O(2) emission occurs, endangering cell functions. The mitochondrial peroxidase peroxiredoxin-3 reduces H(2)O(2) to water using reducing equivalents from NADPH supplied by thioredoxin-2 (Trx2) and, ultimately, thioredoxin reductase-2 (TrxR2).

Sonodynamic effect of an anti-inflammatory agent--emodin on macrophages.

Emodin has been used as an anti-inflammatory agent and inflammation is a crucial feature of atherosclerosis. Here, we investigated the sonodynamic effect of emodin on macrophages, the pivotal inflammatory cells in atherosclerotic plaque. THP-1 derived macrophages were cultured with emodin and exposed to ultrasound.

Hematoporphyrin monomethyl ether-mediated photodynamic effects on THP-1 cell-derived macrophages.

Photodynamic therapy (PDT) has been shown to attenuate atherosclerotic plaque progression and decrease macrophage-infiltration. The effectiveness of PDT depends strongly on the type of photosensitizers. Hematoporphyrin monomethyl ether (HMME) is a promising second-generation porphyrin-related photosensitizer for PDT.