Sinus of Valsalva Aneurysm: An Atypical Etiology of Recurrent Syncope.

The sinus of Valsalva presents the initial segment of the aorta from where the coronary vessels arise. Sinus of Valsalva aneurysms (SOVAs) present as progressive dilatation of the aortic sinus. SOVA arises both from the congenital and acquired weakness of the elastic lamina of the aortic media. Though most of the SOVAs are asymptomatic and diagnosed on screening for other pathologies, patients can present with symptoms of arrhythmia, aortic insufficiency, aorto-cardiac fistulas, and, in a few cases, with rupture. We describe a patient who presented with recurrent syncope and was found to have a 6 cm dilated SOVA with an ectatic ascending aorta. Further assessment revealed a left anterior fascicular block, aortic regurgitation, and mitral regurgitation. On further assessment, no other cause of syncope was found. There was no family history of aneurysm or sudden cardiac death. The patient was eventually discharged with outpatient follow-up with cardiothoracic surgery. In patients presenting with asymptomatic SOVA, a dilatation with a maximum diameter of 6.0 cm requires stringent monitoring and should be considered for surgery.

Wnt7a deficit is associated with dysfunctional angiogenesis in pulmonary arterial hypertension.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is characterised by loss of microvessels. The Wnt pathways control pulmonary angiogenesis but their role in PAH is incompletely understood. We hypothesised that Wnt activation in pulmonary microvascular endothelial cells (PMVECs) is required for pulmonary angiogenesis, and its loss contributes to PAH. METHODS: Lung tissue and PMVECs from healthy and PAH patients were screened for Wnt production. Global and endothelial-specific Wnt7a -/- mice were generated and exposed to chronic hypoxia and Sugen-hypoxia (SuHx). RESULTS: Healthy PMVECs demonstrated >6-fold Wnt7a expression during angiogenesis that was absent in PAH PMVECs and lungs. Wnt7a expression correlated with the formation of tip cells, a migratory endothelial phenotype critical for angiogenesis. PAH PMVECs demonstrated reduced vascular endothelial growth factor (VEGF)-induced tip cell formation as evidenced by reduced filopodia formation and motility, which was partially rescued by recombinant Wnt7a. We discovered that Wnt7a promotes VEGF signalling by facilitating Y1175 tyrosine phosphorylation in vascular endothelial growth factor receptor 2 (VEGFR2) through receptor tyrosine kinase-like orphan receptor 2 (ROR2), a Wnt-specific receptor. We found that ROR2 knockdown mimics Wnt7a insufficiency and prevents recovery of tip cell formation with Wnt7a stimulation. While there was no difference between wild-type and endothelial-specific Wnt7a -/- mice under either chronic hypoxia or SuHx, global Wnt7a +/- mice in hypoxia demonstrated higher pulmonary pressures and severe right ventricular and lung vascular remodelling. Similar to PAH, Wnt7a +/- PMVECs exhibited an insufficient angiogenic response to VEGF-A that improved with Wnt7a. CONCLUSIONS: Wnt7a promotes VEGF signalling in lung PMVECs and its loss is associated with an insufficient VEGF-A angiogenic response. We propose that Wnt7a deficiency contributes to progressive small vessel loss in PAH.