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. 2022 Aug 2;146(5):429-431.
doi: 10.1161/CIRCULATIONAHA.121.058427. Epub 2022 Aug 1.

von Willebrand Factor Is Produced Exclusively by Endothelium, Not Neointima, in Occlusive Vascular Lesions in Both Pulmonary Hypertension and Atherosclerosis

Lea C Steffes  1 , Paul Cheng  2 , Thomas Quertermous  2 , Maya E Kumar  1
Affiliations

von Willebrand Factor Is Produced Exclusively by Endothelium, Not Neointima, in Occlusive Vascular Lesions in Both Pulmonary Hypertension and Atherosclerosis

Lea C Steffes et al. Circulation. .
No abstract available

Keywords: hypertension, pulmonary; models, animal; vascular remodeling; von Willebrand Factor.

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Conflict of interest statement

Conflict of interest disclosures:

None.

Figures

Figure 1
Figure 1. von Willebrand Factor is produced exclusively by endothelium in neointimal lesions of both pulmonary arteries and atherosclerosis aortic root.
vWF protein (red) is detected in both the endothelium (white) and neointima (green) of pulmonary arteries with neointimal lesions (bounded by yellow dashed lines) in rodent models of PH (A), human pulmonary arterial hypertension (PAH, E), and in the aortic root of the ApoE−/− mouse model of atherosclerosis by IHC (H). Neointimal vWF protein is indicated by white arrowheads. In situ hybridization identifies transcripts of the VWF/Vwf gene (red) only in endothelial cells (CLDN15/Cldn5 mRNA, white) and not neointima cells (green) in multiple animal models of PH (B, HDM mouse; C, Sugen-hypoxia rat; D, Tie2-Cre PHD2 mouse), human PAH pulmonary arteries (F & G), and aortic root atherosclerosis (I). The diameter of pulmonary arteries evaluated for mouse & rat were 20–150µm, and human 50–200µm. J, Schematic of artery cross section with neointimal lesion showing proposed model in which vWF protein (red) is secreted from endothelial cells and bound to neointimal ECM. Neointima cells and smooth muscle media, green; endothelium, red; elastic laminae, heavy gray lines. The atherosclerosis mouse model is a constitutive knockout of ApoE transitioned onto a high fat (Western) diet at 8 weeks old that was then sustained for 16 weeks. Neointima and vascular smooth muscle cells identified by antibody staining for Acta2/ACTA2 (clone 1A4; Sigma F3777) for panels A-G and by Myh11-CreER;tdTomato lineage trace for panels H & I. Endothelium in A & H identified by antibody staining for CD31 (BD Pharmingen, 550274) and in E for VE-cadherin (R&D Systems, AF938). vWF antibody in A, E & H from AbCam (ab6994). In situ probes (all RNAscope from ACD): human VWF (560461), human CLDN5 (517141), mouse Vwf (858851), mouse Cldn5 (491611), rat Vwf (413401), and rat Cldn5 (1055891).
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References

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