Abstract：
BACKGROUND:Dipeptidyl peptidase-4 (DPP-4) inhibitors have vasoprotective effects. This study investigated whether a recently approved DPP-4 inhibitor, linagliptin (Lina), suppresses atherogenesis in non-diabetic apolipoprotein-E deficient (ApoE(-/-)) mice, and examined its effects on endothelial function. METHODS AND RESULTS:Lina (10mg/kg/day) was administered orally to ApoE(-/-) mice for 20 weeks. Lina reduced atherogenesis without alteration of metabolic parameters including blood glucose level compared with control (P<0.05). Results of immunohistochemical analyses and quantitative RT-PCR demonstrated that Lina significantly decreased inflammatory molecule expression and macrophage infiltration in the atherosclerotic aorta. Lina administration to ApoE(-/-) mice for 9 weeks ameliorated endothelium-dependent vasodilation compared with that in untreated mice. Plasma active glucagon-like peptide-1 (GLP-1) level was significantly higher in the treated group (P<0.05). Exendin-4 (Ex-4), a GLP-1 analog, ameliorated endothelium-dependent vasodilation impaired by palmitic acid (PA) in wild-type mouse aortic segments. Ex-4 promoted phosphorylation of eNOS(Ser1177) and Akt, both of which were abrogated by PA, in human umbilical vein endothelial cells. In addition, Lina administration to ApoE(-/-) mice decreased oxidative stress, as determined by urinary 8-OHdG secretion and NADPH oxidase subunit expression in the abdominal aorta. CONCLUSION:Lina inhibited atherogenesis in non-diabetic ApoE(-/-) mice. Amelioration of endothelial dysfunction associated with a reduction of oxidative stress by GLP-1 contributes to the atheroprotective effects of Lina.
journal_name
Vascul Pharmacoljournal_title
Vascular pharmacologyauthors
Salim HM,Fukuda D,Higashikuni Y,Tanaka K,Hirata Y,Yagi S,Soeki T,Shimabukuro M,Sata Mdoi
10.1016/j.vph.2015.08.011subject
Has Abstractpub_date
2016-04-01 00:00:00pages
16-23eissn
1537-1891issn
1879-3649pii
S1537-1891(15)00197-4journal_volume
79pub_type
杂志文章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：:Successful drug delivery to the central nervous system (CNS) is highly dependent on DMPK as well as physicochemical properties and it is therefore important to characterise these properties and take them into account when designing chemical lead series that act at CNS targets. Since the drug discovery/development proc...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/s1537-1891(02)00203-3
更新日期：2002-06-01 00:00:00
abstract：:Unresolved endoplasmic reticulum (ER) stress, with the subsequent persistent activation of the unfolded protein response (UPR) is a well-recognized mechanism of endothelial cell apoptosis with a major impact on the integrity of the endothelium during the course of cardiovascular diseases. As in other cell types, Ca(2+...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2015.07.011
更新日期：2016-01-01 00:00:00
abstract：:Angiogenesis consists in the growth of new blood vessels from pre-existing ones. Although anti-angiogenesis interventions have been shown to have therapeutic properties in human diseases such as cancer, their effect is only partial and the identification of novel modulators of angiogenesis is warranted. Recently, we r...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2011.04.001
更新日期：2011-07-01 00:00:00
abstract：:Increased TNFα-mediated JNK signaling in the perivascular adipose tissue (PVAT) may contribute to the pathogenesis of vascular complications in T1DM by reducing adiponectin (Ad) synthesis and therefore impairing Ad-mediated activity in the contiguous blood vessel system. We evaluated whether in vivo treatment with the...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2016.08.007
更新日期：2016-12-01 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：:A small amount of adipose tissue associated with small arteries and arterioles is encountered both in mice and man. This perivascular adipose tissue (PVAT) has a paracrine effect on the vascular tone regulation. PVAT is expanded in obesity and in diabetes. This expansion not only involves enlargement of fat cells, but...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2012.02.003
更新日期：2012-05-01 00:00:00
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, antiat...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2013.07.001
更新日期：2013-09-01 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：OBJECTIVE:The major objective of the present study was to examine the cardioprotective effect of resveratrol, an antioxidant presents in red wine, in the rat after ischemia-reperfusion (I/R). DESIGN:The left coronary artery was in occlusion for 30 min followed by a 120 min reperfusion in anesthetized rats. Animals wer...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2006.04.002
更新日期：2006-08-01 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：:In this study, we have investigated the actions of danshensu, an active, water-extractable component of the medicinal herb danshen (Salvia miltiorrhiza), on rat isolated coronary artery rings precontracted with 1 microM 5-hydroxytryptamine (5-HT) and its action compared to the water-extractable fraction of the herb. E...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2006.10.011
更新日期：2007-04-01 00:00:00
abstract：:Poorly controlled diabetes in pregnancy, characterized by hypo- and hyperglycemia, is associated with adverse outcomes. We hypothesized that aberrant glucose levels affect vascular function in pregnancy. The effects of glucose concentration on constriction and endothelium-dependent relaxation in uterine arteries of no...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2006.09.001
更新日期：2007-02-01 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：:MicroRNAs (miRNAs) have emerged as crucial players regulating the magnitude of gene expression in a variety of organisms. This class of short (22 nucleotides) noncoding RNA molecules have been shown to participate in almost every cellular process investigated so far, and their deregulation is observed in different hum...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2011.07.004
更新日期：2011-10-01 00:00:00
abstract：:Hypertension is a predominant risk factor for cardiovascular diseases and a major health care burden. Accumulating epidemiological and experimental evidence suggest that adult-onset hypertension may have its origins during early development. Upon exposure to glucocorticoids, the fetus develops hypertension, and the of...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2016.02.002
更新日期：2016-07-01 00:00:00
abstract：:Numerous studies of acetylcholine (ACh)-induced endothelium-dependent relaxation in arteries have been reported since the original description by Furchgott and Zawadzki (1980). ACh also produces endothelium-independent relaxation. However, it is still unknown whether ACh-induced AMP-activated protein kinase (AMPK) act...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2013.07.007
更新日期：2013-09-01 00:00:00
abstract：:The present study investigates the potential of ozagrel, a thromboxane A2 (TXA2) synthase inhibitor, in bilateral common carotid artery occlusion (BCCAo) induced vascular dementia (VaD). Wistar rats were subjected to BCCAo procedure under anesthesia to induce VaD. Morris water maze (MWM) test was employed on 7th day p...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2020.106827
更新日期：2020-12-17 00:00:00
abstract：:Endothelin (ET-1) is chronically elevated in diabetes. However, role of ET-1 in increased oxidative stress in type 2 diabetes is less clear. This study tested the hypotheses that: 1) oxidative stress markers are increased and total antioxidant capacity is decreased in diabetes, and 2) activation of ET(A) receptors med...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2007.05.006
更新日期：2007-08-01 00:00:00
abstract：:The key for the survival of all organisms is the regulation and control of energy metabolism. Thus, several strategies have evolved in each tissue in order to balance nutrient supply with energy demand. Adenosine monophosphate-activated protein kinase (AMPK) is now recognized as a key participant in energy metabolism....
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2015.02.017
更新日期：2015-04-01 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：:Doxorubicin (DXR) is a widely used cytostatic agent, but its administration is limited by its cardiovascular side effects. The endothelium is one of the largest organs in the human body and due to its direct contact with blood; it is exposed to the toxic effects of DXR. The aim of this study was to investigate in endo...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2010.08.001
更新日期：2010-11-01 00:00:00
abstract：:We investigated the effects of epinephrine and dopamine on retinal blood vessels in streptozotocin (STZ, 80 mg/kg, i.p.)-treated rats and age-matched control rats to determine whether diabetes mellitus alters the retinal vascular responses to circulating catecholamines. Experiments were performed 6-8 weeks after treat...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2008.06.001
更新日期：2008-08-01 00:00:00
abstract：:The purpose of the present study was to investigate whether SNF472, the hexasodium salt of myo-inositol hexaphosphate (IP6 or phytate): 1. Inhibits induced calcification in cultured aortic valve interstitial cells (VIC) as an in vitro model of aortic valve stenosis and 2. Whether inhibition is different in VIC obtaine...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2019.106583
更新日期：2019-01-01 00:00:00
abstract：:We have studied the therapeutic efficacy of the sodium alginate in experimental immune complex glomerulonephritis. Bovine serum albumin (BSA) nephritis was induced in rats by a subcutaneous immunization and daily intravenous administration of BSA. Sodium alginate at two different doses (25 and 50 mg/kg) was administer...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2005.03.002
更新日期：2005-06-01 00:00:00
abstract：BACKGROUND:Altered endothelial cell (EC)-derived mediator levels, including increased endothelin-1 (ET-1), are hallmarks of human pulmonary arterial hypertension (PAH). Gene mutations for receptors for bone morphogenic proteins (BMP), or transforming growth factor-beta (TGF-beta) cause heritable PAH. The effects of BMP...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2008.09.001
更新日期：2009-01-01 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
abstract：:Much has been written about the potential of pharmacogenetic testing to inform therapy based on an individual's genetic makeup, and to decide the most effective choice of available drugs, or to avoid dangerous side effects. Currently, there is little hard data for either in the field of cardiovascular disease. The usu...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2005.10.003
更新日期：2006-02-01 00:00:00
abstract：:Angiogenesis has become an attractive target for the treatment of certain diseases such as cancer and rheumatoid arthritis. Our previous studies demonstrated that the saponin fraction from Gleditsia sinensis fruits had anti-angiogenic potential, and Gleditsiosides B (GB) was probably the main active constituent. In th...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2012.09.006
更新日期：2013-01-01 00:00:00
abstract：BACKGROUND:Suboptimal platelet inhibition still represents an important challenge, especially for patients undergoing percutaneous coronary interventions (PCI). Chronic kidney disease (CKD) is a common comorbidity of patients with coronary artery disease, and may potentially influence platelet reactivity. So far only f...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2015.10.006
更新日期：2016-04-01 00:00:00
