Fig. 5.

a Extracellular domain cleavage of VEGFR-2 by SHR plasma, MMP-7 and MMP-9. VEGFR-2 immunolabel density was measured after acute treatment (for 6 h) of Wistar heart muscle sections with plasma from WKY and SHR, and with purified MMP −7 and MMP-9. There is extensive cleavage of the extracellular domain of VEGFR-2 on naïve endothelial cells (arrows). All receptor cleavage by SHR plasma, MMP-7, and MMP-9 was blocked by addition of doxycycline (11.3 μM, see with doxycycline group) as well as GM6001 (1 μM), EDTA (10 mM; not shown). Measurements are derived from 4 repeats per plasma/MMP group and 8 arterioles per Wistar cardiac section. * p < 0.05 between SHR plasma, MMPs and WKY plasma; ** p < 0.05 compared to case with doxycycline treatment. b Reversal of VEGFR-2 cleavage in the SHR by chronic MMP inhibition. VEGFR-2 label density was measured in the SHR and WKY without (control groups) and with chronic MMP inhibition (doxycycline, 5.4 mg/kg/day, 24 weeks; doxycycline group). The SHR exhibits many sites of significantly reduced VEGFR-2 labeling (on average about 19%) on the extracellular domain (left images, arrows). There are no differences in VEGFR-2 expression and receptor cleavage in cardiac arterial endothelium detected between WKY rats and SHRs after treatment with the MMP inhibitor. Measurements are derived from 4 rats/group and 8 cardiac artery cross-sections/heart. * p < 0.05 comparison of the extracellular domain of VEGFR-2 density between SHR and WKY; ** p < 0.05 comparison of the extracellular domain of VEGFR-2 density between SHR and SHR + doxycycline.