Divergent effects of quercetin conjugates on angiogenesis

The present study reports the activities of quercetin and its main circulating conjugates in man (quercetin-3′-sulphate (Q3′S) and quercetin-3-glucuronide (Q3G)) on in vivo angiogenesis induced by vascular endothelial growth factor (VEGF) and examines the effects of these molecules on cultured endothelial cells. We found opposing effects of quercetin and its metabolites on angiogenesis. While quercetin and Q3G inhibited VEGF-induced endothelial cell functions and angiogenesis, Q3′S per se promoted endothelial cell proliferation and angiogenesis. The inhibitory effect elicited by Q3G was linked to inhibition of extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation elicited by VEGF. The activation of endothelial cells by Q3′S was associated to stimulation of VEGF receptor-2 and to downstream signalling activation (phosphatidylinositol-3 kinase/Akt and nitric oxide synthase pathways), ultimately responsible for ERK1/2 phosphorylation. These data indicate that the effects of circulating quercetin conjugates on angiogenesis are different depending on the nature of the conjugate. Q3G andQ3′S are the two major conjugates in plasma, but their ratio is dependenton several factors, so thatinhibition or activation of angiogenesis could be subtly shifted as a result of metabolismin viv

Divergent effects of quercetin conjugates on angiogenesis.

The present study reports the activities of quercetin and its main circulating conjugates in man (quercetin-3'-sulphate (Q3'S) and quercetin-3-glucuronide (Q3G)) on in vivo angiogenesis induced by vascular endothelial growth factor (VEGF) and examines the effects of these molecules on cultured endothelial cells. We found opposing effects of quercetin and its metabolites on angiogenesis. While quercetin and Q3G inhibited VEGF-induced endothelial cell functions and angiogenesis, Q3'S per se promoted endothelial cell proliferation and angiogenesis. The inhibitory effect elicited by Q3G was linked to inhibition of extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation elicited by VEGF. The activation of endothelial cells by Q3'S was associated to stimulation of VEGF receptor-2 and to downstream signalling activation (phosphatidylinositol-3 kinase/Akt and nitric oxide synthase pathways), ultimately responsible for ERK1/2 phosphorylation. These data indicate that the effects of circulating quercetin conjugates on angiogenesis are different depending on the nature of the conjugate. Q3G and Q3'S are the two major conjugates in plasma, but their ratio is dependent on several factors, so that inhibition or activation of angiogenesis could be subtly shifted as a result of metabolism in vivo

Perioperative Right Ventricular Dysfunction and Abnormalities of the Tricuspid Valve Apparatus in Patients Undergoing Cardiac Surgery

Right ventricular (RV) dysfunction frequently occurs after cardiac surgery and is linked to adverse postoperative outcomes, including mortality, reintubation, stroke, and prolonged ICU stays. While various criteria using echocardiography and hemodynamic parameters have been proposed, a consensus remains elusive. Distinctive RV anatomical features include its thin wall, which presents a triangular shape in a lateral view and a crescent shape in a cross-sectional view. Principal causes of RV dysfunction after cardiac surgery encompass ischemic reperfusion injury, prolonged ischemic time, choice of cardioplegia and its administration, cardiopulmonary bypass weaning characteristics, and preoperative risk factors. Post-left ventricular assist device (LVAD) implantation RV dysfunction is common but often transient, with a favorable prognosis upon resolution. There is an ongoing debate regarding the benefits of concomitant surgical repair of the RV in the presence of regurgitation. According to the literature, the gold standard techniques for assessing RV function are cardiac magnetic resonance imaging and hemodynamic assessment using thermodilution. Echocardiography is widely favored for perioperative RV function evaluation due to its accessibility, reproducibility, non-invasiveness, and cost-effectiveness. Although other techniques exist for RV function assessment, they are less common in clinical practice. Clinical management strategies focus on early detection and include intravenous drugs (inotropes and vasodilators), inhalation drugs (pulmonary vasodilators), ventilator strategies, volume management, and mechanical support. Bridging research gaps in this field is crucial to improving clinical outcomes associated with RV dysfunction in the near future