Role of antiangiogenic VEGF-A165b in angiogenesis and systolic function after reperfused myocardial infarction

Abstract Introduction and objectives Angiogenesis helps to reestablish microcirculation after myocardial infarction (MI). In this study, we aimed to further understand the role of the antiangiogenic isoform vascular endothelial growth factor (VEGF)-A165b after MI and to explore its potential as a coadjuvant therapy to coronary reperfusion. Methods Two mice MI models were formed: a) permanent coronary ligation (nonreperfused MI); b) transient 45-minute coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. We determined serum and myocardial VEGF-A165b levels. In both experimental MI models…

Angiotensin-(1-7) attenuates endothelial cell senescence via klotho and Nrf2 activation

The rxr agonist bexarotene in combination with rosuvastatin inhibits angiotensin-ii induced abdominal aortic aneurysm formation in apoliprotein -e-knockout mice

Enhanced levels of the light/lymphotoxin-beta receptor inflammatory axis in metabolic syndrome patients

Implicación de la isoforma antiangiogénica VEGF-A165b en la angiogénesis y la función sistólica tras un infarto de miocardio reperfundido

Resumen Introduccion y objetivos La angiogenesis participa en la restauracion de la microcirculacion despues de un infarto agudo de miocardio (IAM). El objetivo de este estudio es explorar el papel que juega la isoforma anti-angiogenica del factor de crecimiento endotelial vascular (VEGF)-A165b y explorar su potencial como terapia coadyuvante a la reperfusion coronaria. Metodos Se realizaron dos modelos murinos de IAM: a) ligadura permanente de la arteria coronaria (IAM no reperfundido) y b) oclusion transitoria durante 45 minutos de la arteria coronaria seguida de reperfusion (IAM reperfundido); en ambos modelos, se realizo a los animales una ecocardiografia previa a la eutanasia el dia 21…

INACTIVATION OF HEPATIC LIPASE DECREASES ATHEROSCLEROSIS IN A MOUSE MODEL OF INSULIN RESISTANCE

Leukotriene B4-loaded microspheres: a new therapeutic strategy to modulate cell activation

AbstractBackgroundLeukotriene B4(LTB4) is a potent inflammatory mediator that also stimulates the immune response. In addition, it promotes polymorphonuclear leukocyte phagocytosis, chemotaxis, chemokinesis and modulates cytokines release. Regarding chemical instability of the leukotriene molecule, in the present study we assessed the immunomodulatory activities conferred by LTB4released from microspheres (MS). A previous oil-in-water emulsion solvent extraction-evaporation method was chosen to prepare LTB4-loaded MS.ResultsIn the mice cremasteric microcirculation, intraescrotal injection of 0.1 ml of LTB4-loaded MS provoked significant increases in leukocyte rolling flux, adhesion and emig…

Synthesis and biological evaluation of sphingosine kinase 2 inhibitors with anti-inflammatory activity.

The synthesis of inhibitors of SphK2 with novel structural scaffolds is reported. These compounds were designed from a molecular modeling study, in which the molecular interactions stabilizing the different complexes were taken into account. Particularly interesting is that 7‐bromo‐2‐(2‐phenylethyl)‐2,3,4,5‐tetrahydro‐1,4‐epoxynaphtho[1,2‐b]azepine, which is a selective inhibitor of SphK2, does not exert any cytotoxic effects and has a potent anti‐inflammatory effect. It was found to inhibit mononuclear cell adhesion to the dysfunctional endothelium with minimal impact on neutrophil–endothelial cell interactions. The information obtained from our theoretical and experimental study can be us…

Disruption of the CCL1-CCR8 axis inhibits vascular Treg recruitment and function and promotes atherosclerosis in mice

The CC chemokine 1 (CCL1, also called I-309 or TCA3) is a potent chemoattractant for leukocytes that plays an important role in inflammatory processes and diseases through binding to its receptor CCR8. Here, we investigated the role of the CCL1-CCR8 axis in atherosclerosis. We found increased expression of CCL1 in the aortas of atherosclerosis-prone fat-fed apolipoprotein E (Apoe)-null mice; moreover, in vitro flow chamber assays and in vivo intravital microscopy demonstrated an essential role for CCL1 in leukocyte recruitment. Mice doubly deficient for CCL1 and Apoe exhibited enhanced atherosclerosis in aorta, which was associated with reduced plasma levels of the anti-inflammatory interle…

Chlorophyll A Fluorescence and Chlorophyll Content in Parmelia Quercina Thalli from a Polluted Region of Northern Castellon (Spain)

AbstractMeasurements of modulated chlorophyll a fluorescence emission and chlorophyll content were made in thalli of Parmelia quercina collected from northern Castellon(Spain). Althoug high air pollution concentrations have been measured in this area, the ratio of variable to maximal fluorescence is unaffected. Following dark-adaptation, the response to irradiance of chlorophyll fluorescence was examined. With respect to control samples, thalli collected in northern Castellon consistently showed differences in fluorescence quenching, the efficiency of excitation energy capture and quenching of basal fluorescence. However, the quantum ield of photochemistry and non-cyclic electron flow were …

Synergistic antiangiogenic activity of bexarotene in combination with rosuvastatin by targeting ang-ii-mediated akt/mtor/p70s6k signaling pathway

Effects of ozone on the foliar histology of the mastic plant (Pistacia lentiscus L.)

[EN] An open-top chamber study was conducted to investigate the tissue and cellular-level foliar effects of ozone (O-3) on a Mediterranean evergreen species, the mastic plant (Pistacia lentiscus L.). Plants were exposed at three different O-3 levels, and leaf samples were collected periodically from the beginning of the exposure. Although no visible foliar injury was evident, alterations of the plastids and vacuoles in the mesophyll were observed. Senescence processes were accelerated with an anomalous stacking of tannin vacuoles, and a reduction in the size and number of the chloroplasts. Overall, most of the modifications induced by O-3 were consistent with previously reported observation…

Physiological,anatomical and biomass partitioning responses to ozone in the Mediterranean endemic plant Lamottea dianae

Ozone effects on the perennial forb Lamottea dianae were studied in an open-top chamber experiment. Ozone was found to induce reductions in CO 2 assimilation and water use efficiency in the leaves of this species. These reductions were mainly related to a decline in the in vivo CO 2 fixation capacity of Rubisco (V c,max), rather than to stomatal limitations or photoinhibitory damage (F v:F m). In addition to chloroplast degeneration, other observed effects were callose accumulation, formation of pectinaceous wart-like cell wall exudates and phloem alterations. Moreover, ozone exposure significantly reduced root dry biomass. The possible relevance of these adverse effects for Mediterranean f…

Implication of anti-angiogenic VEGF-A165b in angiogenesis and systolic function after reperfused myocardial infarction

Abstract Background Angiogenesis participates in re-establishing microcirculation after myocardial infarction (MI). Purpose In this study, we aim to further understand the role of the anti-angiogenic isoform vascular endothelial growth factor (VEGF)-A165b after MI and explore its potential as a co-adjuvant therapy to coronary reperfusion. Methods Two mice MI models were formed: 1) permanent coronary ligation (non-reperfused MI), 2) transient 45-min coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. Serum and myocardial VEGF-A165b levels were determined. In both experimental MI models,…

Combined treatment with bexarotene and rosuvastatin reduces angiotensin-II-induced abdominal aortic aneurysm in apoE−/−mice and angiogenesis

Background and Purpose Abdominal aortic aneurysm (AAA) is a degenerative vascular disease associated with angiogenesis. Bexarotene is a retinoid X receptor (RXR) ligand with anti-angiogenic activity. Statins also exert anti-angiogenic activity and activate PPARs. Because RXR ligands form permissive heterodimers with PPARs and a single anti-angiogenic drug may not be sufficient to combat the wide array of angiogenic factors produced during AAA, we evaluated the effect of combined low doses of bexarotene and rosuvastatin in a mouse model of AAA.

Intravital Microscopy in the Cremaster Muscle Microcirculation for Endothelial Dysfunction Studies

The intravital microscopy in the mouse cremaster muscle microcirculation is a method widely used to visualize in vivo blood cells interacting with the endothelium and within the vessels. Therefore, it is a suitable technique to study leukocyte-endothelial cell interactions along every stage of the canonical leukocyte recruitment cascade: rolling, adhesion, intravascular crawling, and migration both in postcapillary venules and arterioles of the mouse cremasteric microcirculation. This technique also enables to assess vessel functionality, since hemodynamic parameters such as shear stress, flow rate, and vasodilatation/vasoconstriction, among other vascular events, can be additionally determ…

The angiotensin (1-7)/MAS receptor axis and vascular cell inflammation

El ratón deficiente en apolipoproteína E, un modelo traslacional para el estudio de la aterosclerosis

Resumen Introduccion La aterosclerosis es una de las principales causas de morbimortalidad en paises desarrollados que presenta varias similitudes histopatologicas con la inflamacion cronica. Los ratones deficientes en apolipoproteina E (apoE -/− ) son ampliamente utilizados en el estudio de los mecanismos implicados en el inicio y el progreso de las lesiones ateroscleroticas. Objetivo Evaluar el impacto en la formacion de la placa de ateroma de una dieta aterogenica en el raton apoE -/− . Material y metodos Ratones apoE -/− de 2 meses de edad fueron sometidos o no a una dieta hipercolesterolemica (10,8% de grasa, 0,75% en colesterol) durante 2 meses adicionales. Se determino el perfil lipi…

Absence of CCR3 receptor accelerates atherosclerosis in apoE-/- mice

Combination of bexarotene and rosuvastatin at sub-optimal doses impairs angiotensin ii-induced arterial mononuclear cell adhesion