Abstract:
:Propionyl-l-carnitine (PLC) is a natural short-chain derivative of l-carnitine (LC), a natural amino acid that plays an important role in fatty acid metabolism. Recent studies suggest that PLC has vascular protective effects. Because of the importance of endothelial nitric oxide synthase (eNOS) and its product, antiatherogenic molecule nitric oxide (NO), in vascular endothelial function, we sought to elucidate that if PLC would stimulate eNOS and its upstream activators Akt and phosphatidylinositol 3-kinase (PI3 Kinase) in cultured human aortic endothelial cells (HAEC). PLC caused eNOS phosphorylation at Ser-1177, and dominant negative Akt and a novel Akt-selective inhibitor MK-2206 inhibited both PLC-mediated phosphorylation and activation of the enzyme. PI3 kinase inhibition also blocked the phosphorylation and activation of eNOS by PLC. Studies with specific drug inhibitors PD173955 and PP2 showed that the non-receptor tyrosine kinase, src, is an upstream stimulator of the PI3 kinase-Akt pathway in this pathway. In addition, PLC significantly decreased intracellular ATP/ADP ratio and activate AMPK, subsequently leading to Src activation. Finally, we demonstrated that the effects of PLC to augment eNOS activity were associated with a net increase in NO release from endothelial cells. NO production following incubation with PLC was abolished in endothelial cells coincubated with L-NAME, PD173955, LY294002, MK-2206 and compound C. In conclusion, PLC, via AMPK/Src-mediated signaling that leads to activation of PI3 kinase and Akt, stimulates eNOS, leading to increased production of NO.
journal_name
Vascul Pharmacoljournal_title
Vascular pharmacologyauthors
Ning WH,Zhao Kdoi
10.1016/j.vph.2013.07.001subject
Has Abstractpub_date
2013-09-01 00:00:00pages
76-82issue
3-4eissn
1537-1891issn
1879-3649pii
S1537-1891(13)00077-3journal_volume
59pub_type
杂志文章abstract::Bemiparin is a low molecular weight heparin (LMWH) indicated for the acute treatment of deep vein thrombosis with or without pulmonary embolism, for the prophylaxis of venous thromboembolism in surgical and non-surgical patients and for the prevention of clotting in the extracorporeal circuit during hemodialysis. Due ...
journal_title:Vascular pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.vph.2014.03.001
更新日期:2014-07-01 00:00:00
abstract::We previously showed that endothelin A (ETA) receptor antagonist BQ-123 partially inhibited cyclopiazonic acid (CPA)-enhanced endothelin-1 (ET-1)-induced contractions suggesting enhancement of ETA receptor internalization in caveolar structures by sarco/endoplasmic reticulum Ca+2 ATPase (SERCA) blockade. Since seroton...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2014.03.008
更新日期:2014-05-01 00:00:00
abstract::This study examined the effects of a novel orally active 14,15-epoxyeicosatrienoic acid analog (EET-A) on blood pressure (BP) and myocardial infarct size (IS) in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats during sustained phase of hypertension. Between days 31 and 35 after clip placement the rats were tre...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2015.08.013
更新日期:2015-10-01 00:00:00
abstract::Arterial hypertension is a condition associated with endothelial dysfunction, accompanied by an imbalance in the production of reactive oxygen species (ROS) and NO. The aim of this study was to investigate and elucidate the possible mechanisms of sildenafil, a selective phosphodiesterase-5 inhibitor, actions on endoth...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2019.106601
更新日期:2020-01-01 00:00:00
abstract::Recent evidence showed that 17 β-estradiol (E₂) decreased cytokine-induced expression of cell adhesion molecules (CAM). Changes in intracellular Ca²+ concentration ([Ca²+](i)) has been shown to be associated with CAM expression in endothelial cells. Here, the effects of E₂ (1 μM, 24 h) on the expression of intracellul...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2010.09.001
更新日期:2010-11-01 00:00:00
abstract::Potassium channel dysfunction plays a role in the pathogenesis of a number of vascular diseases including pulmonary and systemic hypertension, diabetes, and complications of atherosclerosis. Two types of K+ channels that are known to be prevalent and contribute significantly to the repolarization of vascular smooth mu...
journal_title:Vascular pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s1537-1891(02)00121-0
更新日期:2002-01-01 00:00:00
abstract::We studied the mechanisms involved in the relaxation induced by nitric oxide (NO) donors, ruthenium complex ([Ru(terpy)(bdq)NO(+)](3+)-TERPY) and sodium nitroprusside (SNP) in denuded rat aorta. Both NO donors induced vascular relaxation independent of the agonist used in the pre-contraction. [Ru(terpy)(bdq)NO(+)](3+)...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2006.10.002
更新日期:2007-03-01 00:00:00
abstract::A large number of studies utilize animal models to investigate therapeutic angiogenesis. However, the lack of a standardized experimental model leaves the comparison of different studies problematic. To establish a reference model of prolonged moderate tissue ischemia, we created unilateral hind limb ischemia in athym...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2009.07.001
更新日期:2009-10-01 00:00:00
abstract::Neurokinin(3) (NK(3)) receptors may regulate the airways primarily through actions on the nerves. In the periphery, airway parasympathetic ganglia neurons are depolarized following NK(3) receptor activation resulting subsequently in the facilitation of synaptic transmission. Such an effect may account for the excessiv...
journal_title:Vascular pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.vph.2005.08.031
更新日期:2006-10-01 00:00:00
abstract::Therapeutic modulation of angiogenesis is believed to be a prospective powerful treatment strategy to modulate the microcirculation and therefore help millions of patients with cardiovascular and cancer diseases. The often-frustrating results from late-stage clinical studies indicate an urgent need for improved assess...
journal_title:Vascular pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.vph.2018.09.003
更新日期:2019-01-01 00:00:00
abstract::The objective of this study was to determine the mechanism by which Na(+)/H(+) exchanger (NHE) inhibitors induce vasodilatation. The NHE inhibitors, 5-(N,N-dimethyl)-amiloride (DMA), cariporide, and amiloride, evoked endothelium-dependent relaxation in rat aortas with ED50 values of 16, 89, and 148μM, respectively, an...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2012.11.004
更新日期:2013-04-01 00:00:00
abstract::Increasing evidences support that PGC-1α participates in regulating endothelial homeostasis, in part by mediating endothelial nitric oxide (NO) synthase (eNOS) activity and NO production. However, the molecular mechanisms by which PGC-1α regulates eNOS activity are not completely understood. In the present study, we i...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2016.05.005
更新日期:2016-08-01 00:00:00
abstract::The prevention of cardiovascular disease is critically dependent on lipid-lowering therapy, including 3-hydroxymethyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), cholesterol absorption inhibitors, bile acid resins, fibrates, and nicotinic acid. Although these drugs are generally well tolerate...
journal_title:Vascular pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.vph.2005.07.012
更新日期:2006-02-01 00:00:00
abstract::β-Adrenoceptors (β-ARs) modulate ERK1/2 and p38 in different cells, but little is known about the contribution of these signaling pathways to the function of β-ARs in vascular tissue. Immunoblotting analysis of rat aortic rings, primary endothelial (ECs) and smooth muscle cells (SMCs) isolated from aorta showed that β...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2014.04.003
更新日期:2014-05-01 00:00:00
abstract::Intra-aortic balloon pump (IABP) counterpulsation has been the most widely used left ventricular assist device for nearly five decades. Due to diastolic inflation and systolic deflation, coronary blood flow is increased and afterload decreased translating into augmentation of oxygen supply and lowering of oxygen deman...
journal_title:Vascular pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.vph.2013.12.003
更新日期:2014-02-01 00:00:00
abstract::In systemic sclerosis, microvascular injury often precedes the development of fibrosis. Whereas the development of digital ulcers and skin fibrosis causes high morbidity, the affection of internal organs, in particular complications such as interstitial lung disease and pulmonary (arterial) hypertension, account for t...
journal_title:Vascular pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.vph.2012.12.001
更新日期:2013-03-01 00:00:00
abstract::Propranolol is a non-selective beta-adrenergic receptor blocker used in the treatment of cardiovascular diseases and migraine prophylaxis. Although it has been shown that propranolol dilates the peripheral arteries of rat, its action in the central nervous system vasculature has not been investigated. In this study, t...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2012.12.004
更新日期:2013-04-01 00:00:00
abstract:OBJECTIVE:Inflammation and oxidative stress play a key role in the initiation, propagation, and development of atherosclerosis. Arterial baroreflex (ABR) dysfunction induced by sinoaortic denervation (SAD) promoted the development of atherosclerosis in ApoE-/- mice. The present work was designed to examine whether ABR ...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2016.08.008
更新日期:2016-12-01 00:00:00
abstract::Lactadherin is a small (53-66kDa) multifunctional glycoprotein belonging to the secreted extracellular matrix protein family. It has a multi-domain structure and is involved in many biological and physiological processes, including phagocytosis, angiogenesis, atherosclerosis, tissue remodeling, and haemostasis regulat...
journal_title:Vascular pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.vph.2017.11.006
更新日期:2018-02-01 00:00:00
abstract::Vasculopathy is common in patients with connective tissue disease and can be directly implicated in the pathogenesis of the disease. Systemic sclerosis is an auto-immune multiorgan connective tissue disorder characterized by fibrosis of the skin and visceral organs and vascular disease. Micro- and macro-vessels are a ...
journal_title:Vascular pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.vph.2015.05.015
更新日期:2015-08-01 00:00:00
abstract::Angiostatin is an angiogenesis inhibitor in part generated by and released from platelets. Since platelets upon thrombus formation can give rise to areas of hypoxia, we investigated the effects of angiostatin on endothelial cell migration and apoptosis during hypoxia. Human microvascular endothelial cells (HMVEC-L) we...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2012.11.003
更新日期:2013-04-01 00:00:00
abstract::The heart is subjected to chronic mechanical unloading during prolonged spaceflight and microgravity. The heart in patients with end-stage heart failure is also unloaded in prolonged duration after left ventricular assist devices (LVAD) are implanted. Heterotopic heart transplantation in rats is an established model o...
journal_title:Vascular pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.vph.2009.10.004
更新日期:2010-03-01 00:00:00
abstract::This study was designed to study the influence of Sacoglottis gabonensis stem bark extract on the metabolic and cytotoxic side effects of 2,4-dinitrophenyl hydrazine (2,4-DNPH) on the brain and blood using male weaving rats as the experimental model. This was after the effect of the bark extract and bergenin, its isol...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/s1537-1891(03)00042-9
更新日期:2002-12-01 00:00:00
abstract::tert-Butyl hydroperoxide (t-BOOH), a membrane permeant oxidant, elicits enhanced vasoconstriction of perfused kidney and mesenteric arterial beds isolated from DOCA-salt-induced hypertensive rats. We hypothesize that enhanced vasoconstriction to t-BOOH during DOCA-salt hypertension involves free radical species and de...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/s1537-1891(02)00309-9
更新日期:2003-01-01 00:00:00
abstract::Ghrelin, a 28-amino acid peptide, known to exist in both acylated and des-acylated varieties, was identified as the first endogenous ligand of growth hormone secretagogue receptor in 1999. Various arteries are known to express ghrelin receptors, but the direct action of ghrelin on blood vessels has been unclear. In th...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2007.03.004
更新日期:2007-07-01 00:00:00
abstract::We characterized vascular reactivity to endothelin-1 (ET-1) in mesenteric vessels from DOCA-salt hypertensive and SHAM control mice and assessed the effect that endothelial-derived vasodilators have on ET-1-induced vasoconstriction. Changes in the diameter of unpressurized small mesenteric arteries and veins (100- to ...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2005.02.014
更新日期:2005-06-01 00:00:00
abstract::Despite a large number of studies, the mechanism by which 3',5'-cyclic monophosphate (cAMP) induces vasorelaxation is not fully understood. The comparison between results obtained in different vessels or species has often been the source of conflicting reports. In order to shed more light onto this mechanism, we studi...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2012.08.007
更新日期:2013-01-01 00:00:00
abstract:OBJECTIVE:In patients with familial combined hyperlipidemia (FCHL), without metabolic syndrome (MS), occurrence of non-alcoholic fatty liver disease (NAFLD) is related to a specific pro-inflammatory profile, influenced by genetic traits, involved in oxidative stress and adipokine secretion. Among FCHL or MS patients, h...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2015.04.004
更新日期:2015-09-01 00:00:00
abstract:BACKGROUND:Macrophages play a central role in atherosclerosis development and progression, hence, targeting macrophage activity is considered an attractive therapeutic. Recently, we documented nanomedicinal delivery of the anti-inflammatory compound prednisolone to atherosclerotic plaque macrophages in patients, which ...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2016.04.006
更新日期:2016-07-01 00:00:00
abstract:BACKGROUND:Platelets play crucial roles in the development of arterial thrombosis and other pathophysiologies leading to clinical ischemic events. Defective regulation of platelet activation/aggregation is a predominant cause for arterial thrombosis. The purposes of the study are to determine whether atherosclerotic pl...
journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2008.03.004
更新日期:2008-07-01 00:00:00