RESUMO
Background: The objective of the present study was to evaluate the bioresorption rate of collagen coating (CC) sealed on textile vascular grafts (VGs) and their healing in humans using histologic analysis of explanted VGs. Methods: A total of 27 polyester textile VGs had been removed during surgery from 2012 to 2020. The segments underwent histologic assessment. The CC bioresorption rate was assessed using morphometric analysis to determine the internal and external capsule thickness, inflammatory reaction degree, presence of neovessels, and endothelial cell layer. Results: A total of 27 VGs were explanted from 25 patients because of infection (n = 5; 18.5%), thrombosis (n = 7; 25.9%), stenosis (n = 2; 7.4%), rupture (n = 4; 14.8%), aneurysmal degeneration (n = 3; 11.1%), revascularization (n = 4; 14.8%), or another cause (n = 2; 7.4%), with a median implantation duration of 291 days (interquartile range [IQR], 48-911 days). VGs with remaining CC (n = 7; 26%) had been explanted earlier than had those without (n = 20; 74%; 1 day [IQR, 1-45 days] vs 516 days [IQR, 79-2018 days]; P = .001). After 1 year, no remaining CC was detected on the analyzed VG sections. VGs implanted for <90 days had had a greater CC maximal thickness (63.90 µm [IQR, 0-83.25 µm] vs 0 µm [IQR, 0-0 µm]; P = .006) and a greater CC surface coverage (180° [IQR, 0°-360°] vs 0° [IQR, 0°-0°]; P = .002) than those implanted for >90 days. VGs implanted for >90 days had a greater external capsule thickness (889.2 µm [IQR, 39.6-1317 µm] vs 0 µm [IQR, 0-0 µm]; P = .002), a higher number of inflammatory mononuclear cells and giant cells (168 cells [IQR, 110-310 cells] vs 0 cells [IQR, 0-94 cells]; P < .0001) and a higher number of neovessels (4 [IQR, 0-5] vs 0 [IQR, 0-0]; P = .001) than those implanted for <90 days. Conclusions: CC had a slow bioresorption rate in humans. Complete healing was never achieved, with no endothelial coverage observed. This finding implies that CC might not help graft healing.
RESUMO
AIMS: BMP9 and BMP10 mutations were recently identified in patients with pulmonary arterial hypertension, but their specific roles in the pathogenesis of the disease are still unclear. We aimed to study the roles of BMP9 and BMP10 in cardiovascular homeostasis and pulmonary hypertension using transgenic mouse models deficient in Bmp9 and/or Bmp10. METHODS AND RESULTS: Single- and double-knockout mice for Bmp9 (constitutive) and/or Bmp10 (tamoxifen inducible) were generated. Single-knock-out (KO) mice developed no obvious age-dependent phenotype when compared with their wild-type littermates. However, combined deficiency in Bmp9 and Bmp10 led to vascular defects resulting in a decrease in peripheral vascular resistance and blood pressure and the progressive development of high-output heart failure and pulmonary hemosiderosis. RNAseq analysis of the lungs of the double-KO mice revealed differential expression of genes involved in inflammation and vascular homeostasis. We next challenged these mice to chronic hypoxia. After 3 weeks of hypoxic exposure, Bmp10-cKO mice showed an enlarged heart. However, although genetic deletion of Bmp9 in the single- and double-KO mice attenuated the muscularization of pulmonary arterioles induced by chronic hypoxia, we observed no differences in Bmp10-cKO mice. Consistent with these results, endothelin-1 levels were significantly reduced in Bmp9 deficient mice but not Bmp10-cKO mice. Furthermore, the effects of BMP9 on vasoconstriction were inhibited by bosentan, an endothelin receptor antagonist, in a chick chorioallantoic membrane assay. CONCLUSIONS: Our data show redundant roles for BMP9 and BMP10 in cardiovascular homeostasis under normoxic conditions (only combined deletion of both Bmp9 and Bmp10 was associated with severe defects) but highlight specific roles under chronic hypoxic conditions. We obtained evidence that BMP9 contributes to chronic hypoxia-induced pulmonary vascular remodelling, whereas BMP10 plays a role in hypoxia-induced cardiac remodelling in mice.
