Fig 2: DEL-1–Fc–treated mice have low MMP2 activity in aorta and heart.Levels of latent pro-MMP2 and active MMP2 in aorta (A and C) and heart (B and C) (n = 6 mice per group). Data are represented as mean ± SEM. *P < 0.05; **P < 0.01, 1-way ANOVA with Bonferroni’s post hoc test to adjust for multiple comparisons.

Fig 3: DEL-1 inhibits αvβ3 integrin–dependent activation of latent pro-MMP2 in isolated human aorta.A piece of isolated human aorta, which was divided into smaller 5 × 5 mm2 pieces and incubated in tissue well plates, followed by pretreatment with plasmas of Fc-, DEL-1–Fc–, and DEL-1–RGE–Fc–injected mice or plasma of EC-Del1 mice and then stimulated with ANGII/ET1 (A and B). In situ gel zymography showing MMP2 activity in isolated human aorta (C and D). MMP2 (E), furin (F), and MT1-MMP (G) activity assays in extracts of isolated human aorta. Schematic summary of protective effects and antiinflammatory mechanisms of action of DEL-1 in ANGII-induced hypertension and cardiovascular remodeling (H) (A–G, n = 4 independent experiments). Data are represented as mean ± SEM. **P < 0.01, 1-way ANOVA with Bonferroni’s post hoc test to adjust for multiple comparisons.

Fig 4: EC-Del1 mice have low MMP2 activity in cardiovascular tissues.Levels of latent pro-MMP2 and active MMP2 in aorta (A and B) and heart (A and C) after 4 weeks of ANGII or vehicle (Veh.) infusion (n = 6–7 mice per group). Data are represented as mean ± SEM. **P < 0.01, 2-way ANOVA with Bonferroni’s post hoc test to adjust for multiple comparisons.

Fig 5: DEL-1 inhibits αvβ3 integrin–dependent activation of latent pro-MMP2.Thoracic aorta was isolated from WT and EC-Del1 mice and stimulated with ANGII/ET1, followed by assessment of latent pro- and active MMP2 (A). Stimulation of isolated aorta from WT and EC-Del1 mice without endothelium (B). ANGII/ET1-stimulated aortas of WT mice pretreated with Fc, DEL-1–Fc, or DEL-1–RGE–Fc (C). ANGII/ET1–stimulated aortas of WT mice pretreated with plasma of EC-Del1 mice (D). Cultured human aortic SMCs pretreated with plasmas of WT mice injected with Fc, DEL-1–Fc, DEL-1–RGE–Fc, or plasma of EC-Del1 mice and then stimulated with ANGII/ET1 (E). Cultured human aortic SMCs pretreated with Fc, DEL-1–Fc, DEL-1–RGE–Fc, or pharmacological αvβ3 integrin cilengitide and then stimulated with ANGII/ET1 (F) (A–F n = 4 independent experiments). Data are represented as mean ± SEM. **P < 0.01, 1-way ANOVA with Bonferroni’s post hoc test to adjust for multiple comparisons.