Search

Wnt16 is expressed in bone and arteries, and maintains bone mass in mice and humans, but its role in cardiovascular physiology is unknown. We show that Wnt16 protein accumulates in murine and human vascular smooth muscle (VSM). WNT16 genotypes that convey risk for bone frailty also convey risk for cardiovascular events in the Dallas Heart Study. Murine Wnt16 deficiency, which causes postnatal bone loss, also reduced systolic blood pressure. Electron microscopy demonstrated abnormal VSM mitochondrial morphology in Wnt16-null mice, with reductions in mitochondrial respiration. Following angiotensin-II (AngII) infusion, thoracic ascending aorta (TAA) dilatation was greater in Wnt16 −/− vs Wnt16+/+ mice (LDLR −/− background). Acta2 (vascular smooth muscle alpha actin) deficiency has been shown to impair contractile phenotype and worsen TAA aneurysm with concomitant reductions in blood pressure. Wnt16 deficiency reduced expression of Acta2 , SM22 (transgelin), and other contractile genes, and reduced VSM contraction induced by TGFβ. Acta2 and SM22 proteins were reduced in Wnt16 −/− VSM as was Ankrd1, a prototypic contractile target of Yap1 and Taz activation via TEA domain (TEAD)-directed transcription. Wnt16 −/− VSM exhibited reduced nuclear Taz and Yap1 protein accumulation. SiRNA targeting Wnt16 or Taz, but not Yap1, phenocopied Wnt16 deficiency, and Taz siRNA inhibited contractile gene upregulation by Wnt16. Wnt16 incubation stimulated mitochondrial respiration and contraction (reversed by verteporfin, a Yap/Taz inhibitor). SiRNA targeting Taz inhibitors Ccm2 and Lats1/2 mimicked Wnt16 treatment. Wnt16 stimulated Taz binding to Acta2 chromatin and H3K4me3 methylation. TEAD cognates in the Acta2 promoter conveyed transcriptional responses to Wnt16 and Taz. Wnt16 regulates cardiovascular physiology and VSM contractile phenotype, mediated via Taz signaling. [ABSTRACT FROM AUTHOR]

Wnt16 is expressed in bone and arteries, and maintains bone mass in mice and humans, but its role in cardiovascular physiology is unknown. We show that Wnt16 protein accumulates in murine and human vascular smooth muscle (VSM). WNT16 genotypes that convey risk for bone frailty also convey risk for cardiovascular events in the Dallas Heart Study. Murine Wnt16 deficiency, which causes postnatal bone loss, also reduced systolic blood pressure. Electron microscopy demonstrated abnormal VSM mitochondrial morphology in Wnt16-null mice, with reductions in mitochondrial respiration. Following angiotensin-II (AngII) infusion, thoracic ascending aorta (TAA) dilatation was greater in Wnt16-/- vs Wnt16+/+ mice (LDLR-/- background). Acta2 (vascular smooth muscle alpha actin) deficiency has been shown to impair contractile phenotype and worsen TAA aneurysm with concomitant reductions in blood pressure. Wnt16 deficiency reduced expression of Acta2, SM22 (transgelin), and other contractile genes, and reduced VSM contraction induced by TGFβ. Acta2 and SM22 proteins were reduced in Wnt16-/- VSM as was Ankrd1, a prototypic contractile target of Yap1 and Taz activation via TEA domain (TEAD)-directed transcription. Wnt16-/- VSM exhibited reduced nuclear Taz and Yap1 protein accumulation. SiRNA targeting Wnt16 or Taz, but not Yap1, phenocopied Wnt16 deficiency, and Taz siRNA inhibited contractile gene upregulation by Wnt16. Wnt16 incubation stimulated mitochondrial respiration and contraction (reversed by verteporfin, a Yap/Taz inhibitor). SiRNA targeting Taz inhibitors Ccm2 and Lats1/2 mimicked Wnt16 treatment. Wnt16 stimulated Taz binding to Acta2 chromatin and H3K4me3 methylation. TEAD cognates in the Acta2 promoter conveyed transcriptional responses to Wnt16 and Taz. Wnt16 regulates cardiovascular physiology and VSM contractile phenotype, mediated via Taz signaling., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate three different methods for controlling presacral massive bleeding during pelvic operations., Methods: Clinical data of 11 patients with presacral massive bleeding during pelvic operation at The Sixth Affiliated Hospital of Sun Yat-sen University and 157 Branch Hospital of Guangzhou General Hospital of Guangzhou Military Command from January 2001 to January 2016 were analyzed retrospectively. Hemostasis methods for presacral massive bleeding during operation included gauze packing (whole pressure), drawing pin (local pressure) and absorbable gauze (absorbable gauze was adhered to bleeding position with medical glue after local pressure). Efficacy of these 3 methods for controlling bleeding was evaluated and compared., Results: Ten patients were male and 1 was female with average age of 65.2 (40 to 79) years old. Eight cases were rectal cancer, 2 were presacral malignancies and 1 was rectal benign lesion. Bleeding volume during operation was 300 to 2 500 (median 800) ml. From 2001 to 2012, 4 cases received gauze packing, of whom, 3 cases were scheduled Dixon resection before operation and then had to be referred to Hartman resection; 3 cases died of systemic failure due to postoperative chronic errhysis and infection, and 1 underwent re-operation. At the same time from 2001 to 2012, 5 cases received drawing pin, of whom, bleeding of 3 cases was successfully controlled and Dixon resection was completed. In other 2 cases with hemostasis failure, 1 case underwent re-operation following the use of gauze packing, and another 1 case received absorbable gauze hemostasis. All the 5 patients were healing. From 2013 to 2016, 2 cases completed scheduled anterior resection of rectum after successful hemostasis with absorbable gauze and were healing and discharged., Conclusions: Gauze packing hemostasis is a basic method for controlling presacral massive bleeding. Drawing pin and absorbable gauze hemostasis are more precise and may avoid the change of surgical procedure. But drawing pin has the possibility of hemostasis failure. Absorbable gauze hemostasis with medical adhesive is effective, simple and fast.