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Grossini E.,University Eastern Piedmont ogadro | Farruggio S.,University Eastern Piedmont ogadro | Qoqaiche F.,University Eastern Piedmont ogadro | Raina G.,University Eastern Piedmont ogadro | And 5 more authors.
Life Sciences | Year: 2016

Aims Perivascular adipose tissue can be involved in the process of cardiovascular pathology through the release of adipokines, namely adiponectins. Monomeric adiponectin has been shown to increase coronary blood flow in anesthetized pigs through increased nitric oxide (NO) release and the involvement of adiponectin receptor 1 (AdipoR1). The present study was therefore planned to examine the effects of monomeric adiponectin on NO release and Ca2 + transients in porcine aortic endothelial cells (PAEs) in normal/high glucose conditions and the related mechanisms. Main methods PAEs were treated with monomeric adiponectin alone or in the presence of intracellular kinases blocker, AdipoR1 and Ca2 +-ATPase pump inhibitors. The role of Na+/Ca2 + exchanger was examined in experiments performed in zero Na+ medium. NO release and intracellular Ca2 + were measured through specific probes. Key findings In PAE cultured in normal glucose conditions, monomeric adiponectin elevated NO production and [Ca2 +]c. Similar effects were observed in high glucose conditions, although the response was lower and not transient. The Ca2 + mobilized by monomeric adiponectin originated from an intracellular pool thapsigargin- and ATP-sensitive and from the extracellular space. Moreover, the effects of monomeric adiponectin were prevented by kinase blockers and AdipoR1 inhibitor. Finally, in normal glucose condition, a role for Na+/Ca2 + exchanger and Ca2 +-ATPase pump in restoring Ca2 + was found. Significance Our results add new information about the control of endothelial function elicited by monomeric adiponectin, which would be achieved by modulation of NO release and Ca2 + transients. A signalling related to Akt, ERK1/2 and p38MAPK downstream AdipoR1 would be involved. © 2016 Elsevier Inc.


Grossini E.,University Eastern Piedmont ogadro | Gramaglia C.,University Eastern Piedmont ogadro | Farruggio S.,University Eastern Piedmont ogadro | Bellofatto K.,University Eastern Piedmont ogadro | And 4 more authors.
Vascular Pharmacology | Year: 2014

Changes in endothelial function and peroxidation could play a significant role in the pathophysiology of cardiovascular disease in psychiatric patients. In particular, endothelial nitric oxide (NO) could either exert a beneficial or detrimental effect depending on the involvement of NO synthase (NOS) subtype. Therefore, we planned to examine the effects of asenapine on NO release and protection against oxidative stress in porcine coronary endothelial cells (CEC). The Griess system and Western blot were used for NO detection and to examine changes in protein activation and expression. In addition, cell oxidative/antioxidant status and mitochondrial membrane potential were measured by specific fluorescent dyes. Asenapine caused a concentration-dependent increase of NO production (p<0.05) by the involvement of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), phospholipase C (PLC), β2-adrenoceptor-related pathway, Akt, extracellular-signal-regulated kinases 1/2 (ERK1/2) and p38 mitogen-activated protein kinases (p38 MAPK). Furthermore, asenapine protected CEC against oxidative stress by preventing reactive oxygen species production and glutathione reduction, mitochondrial membrane potential collapse and apoptosis, and by modulation of the inducible NOS (iNOS). In conclusion, in CEC asenapine induced eNOS-dependent NO production through an intracellular signaling leading to Akt, ERK1/2 and p38MAPK activation. Moreover, asenapine protected CEC against oxidative stress by modulation of antioxidant system, apoptosis, cell survival signaling and mitochondria functioning. © 2014 Elsevier Inc.


Grossini E.,University Eastern Piedmont ogadro | Prodam F.,Azienda Ospedaliera Universitaria Maggiore della Carita | Prodam F.,Health Science University | Walker G.E.,Azienda Ospedaliera Universitaria Maggiore della Carita | And 10 more authors.
Journal of Endocrinology | Year: 2014

Adiponectin, the most abundant adipokine released by adipose tissue, appears to play an important role in the regulation of vascular endothelial and cardiac function. To date, however, the physiological effects of human monomeric adiponectin on the coronary vasculature andmyocardial systo-diastolic function, as well asonparasympathetic/sympathetic involvement and nitric oxide (NO) release, have not yet been investigated. Thus, weplanned to determine the primary in vivo effects of human monomeric adiponectin on coronary blood flow and cardiac contractility/relaxation and the related role of autonomic nervous system, adiponectin receptors, and NO. In 30 anesthetized pigs, human monomeric adiponectin was infused into the left anterior descending coronary artery at constant heart rate and arterial bloodpressure, and the effectsoncoronary bloodflow, left ventricular systo-diastolic function, myocardial oxygen metabolism, and NO release were examined. The mechanisms of the observedhemodynamic responses were also analyzed by repeating the highest dose of human monomeric adiponectin infusion after autonomic nervous systemand NO blockade, and after specific adiponectin 1 receptor antagonist administration. Intracoronary human monomeric adiponectin caused dose-related increases of coronary blood flowand cardiac function. Those effects were accompanied by increased coronary NO release and coronary adiponectin levels. Moreover, the vascular effects of the peptide were prevented by blockade of β2-adrenoceptors and NO synthase, whereas all effects of human monomeric adiponectin were prevented by adiponectin 1 receptor inhibitor. In conclusion, human monomeric adiponectin primarily increased coronary blood flow and cardiac systo-diastolic function through the involvement of specific receptors, β2-adrenoceptors, and NO release. © 2014 Society for Endocrinology.


Perivascular adipose tissue can be involved in the process of cardiovascular pathology through the release of adipokines, namely adiponectins. Monomeric adiponectin has been shown to increase coronary blood flow in anesthetized pigs through increased nitric oxide (NO) release and the involvement of adiponectin receptor 1 (AdipoR1). The present study was therefore planned to examine the effects of monomeric adiponectin on NO release and Ca(2+) transients in porcine aortic endothelial cells (PAEs) in normal/high glucose conditions and the related mechanisms.PAEs were treated with monomeric adiponectin alone or in the presence of intracellular kinases blocker, AdipoR1 and Ca(2+)-ATPase pump inhibitors. The role of Na(+)/Ca(2+) exchanger was examined in experiments performed in zero Na(+) medium. NO release and intracellular Ca(2+) were measured through specific probes.In PAE cultured in normal glucose conditions, monomeric adiponectin elevated NO production and [Ca(2+)]c. Similar effects were observed in high glucose conditions, although the response was lower and not transient. The Ca(2+) mobilized by monomeric adiponectin originated from an intracellular pool thapsigargin- and ATP-sensitive and from the extracellular space. Moreover, the effects of monomeric adiponectin were prevented by kinase blockers and AdipoR1 inhibitor. Finally, in normal glucose condition, a role for Na(+)/Ca(2+) exchanger and Ca(2+)-ATPase pump in restoring Ca(2+) was found.Our results add new information about the control of endothelial function elicited by monomeric adiponectin, which would be achieved by modulation of NO release and Ca(2+) transients. A signalling related to Akt, ERK1/2 and p38MAPK downstream AdipoR1 would be involved.


PubMed | University Eastern Piedmont ogadro
Type: Journal Article | Journal: Vascular pharmacology | Year: 2014

Changes in endothelial function and peroxidation could play a significant role in the pathophysiology of cardiovascular disease in psychiatric patients. In particular, endothelial nitric oxide (NO) could either exert a beneficial or detrimental effect depending on the involvement of NO synthase (NOS) subtype. Therefore, we planned to examine the effects of asenapine on NO release and protection against oxidative stress in porcine coronary endothelial cells (CEC). The Griess system and Western blot were used for NO detection and to examine changes in protein activation and expression. In addition, cell oxidative/antioxidant status and mitochondrial membrane potential were measured by specific fluorescent dyes. Asenapine caused a concentration-dependent increase of NO production (p<0.05) by the involvement of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), phospholipase C (PLC), 2-adrenoceptor-related pathway, Akt, extracellular-signal-regulated kinases 1/2 (ERK1/2) and p38 mitogen-activated protein kinases (p38 MAPK). Furthermore, asenapine protected CEC against oxidative stress by preventing reactive oxygen species production and glutathione reduction, mitochondrial membrane potential collapse and apoptosis, and by modulation of the inducible NOS (iNOS). In conclusion, in CEC asenapine induced eNOS-dependent NO production through an intracellular signaling leading to Akt, ERK1/2 and p38MAPK activation. Moreover, asenapine protected CEC against oxidative stress by modulation of antioxidant system, apoptosis, cell survival signaling and mitochondria functioning.

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