Endothelial cell dysfunction and retinal arteriolar narrowing in young adults with elevated blood pressure

Tan, C.; Lewandowski, A. J.; Hanssen, H.; Streese, L.; Huckstep, O.; Fischer, R.; Alsharqi, M.; Mohamed, A.; Williamson, W.; Leeson, P.; Bertagnolli, M.

doi:10.1101/2024.07.12.603349

bioRxiv · 10.1101/2024.07.12.603349

Endothelial cell dysfunction and retinal arteriolar narrowing in young adults with elevated blood pressure

Tan, C.·Lewandowski, A. J.·Hanssen, H.·Streese, L.·Huckstep, O.·Fischer, R.·Alsharqi, M.·Mohamed, A.·Williamson, W.·Leeson, P.·Bertagnolli, M.

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Abstract

BackgroundYoung-adults with endothelial cell dysfunction are more likely to develop elevated blood pressure. We tested the hypothesis that this relates to development of structural microvascular impairments by studying associations between circulating endothelial colony-forming cell (ECFC) dysfunction and microvascular markers, as well as identifying related endothelial molecular mechanisms. MethodsPeripheral blood ECFCs were isolated from 32 subjects (53% men, 28{+/-}4 years old) using the Ficoll density gradient centrifugation method. Participants with blood pressure [≥]120/80 mm Hg were included in the elevated blood pressure (BP) group, whereas [≤]120/80 mm Hg were classed as normotensive. Retinal microvasculature was assessed by Static Retinal Vessel Analyzer (SVA-T). ResultsSubjects with elevated BP had impaired in vitro ECFC colony-forming growth, cell proliferation and angiogenesis assessed by tube formation potential. There was a graded inverse association between ECFC colony-forming capacity (days taken for ECFC colony growth) and retinal arteriolar diameter, as well as arteriolar/venular ratio. Proteomic analysis of ECFCs identified differences in extracellular matrix organization, blood coagulation, exocytosis and vesicle transport proteins in subjects with elevated blood pressure, revealing the adaptor protein GRB2 as a potential link between endothelial cell and microvascular abnormalities. ConclusionsEndothelial cell dysfunction associates with retinal arteriolar narrowing in men and women with elevated blood pressure. Endothelial molecular mechanisms linked to reduced adaptive postnatal angiogenesis capacity, rather than vascular development, may contribute to early microvascular changes. HIGHLIGHTSO_LISubjects with elevated blood pressure had impaired in vitro endothelial cell growth and angiogenesis in comparison to normotensive subjects. C_LIO_LIThere was an association between impaired endothelial cell growth capacity and reduced retinal arteriolar diameter. C_LIO_LIDifferent endothelial proteome signatures were identified, revealing the adaptor protein GRB2 as a potential link between endothelial and microvascular abnormalities in subjects with elevated blood pressure. C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/603349v1_ufig1.gif" ALT="Figure 1"> View larger version (71K): org.highwire.dtl.DTLVardef@9c28aborg.highwire.dtl.DTLVardef@3212a9org.highwire.dtl.DTLVardef@16755f9org.highwire.dtl.DTLVardef@13d5341_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Tan, C., Lewandowski, A. J., Hanssen, H., Streese, L., Huckstep, O., Fischer, R., Alsharqi, M., Mohamed, A., Williamson, W., Leeson, P., Bertagnolli, M.. 2024-07-19. Endothelial cell dysfunction and retinal arteriolar narrowing in young adults with elevated blood pressure. https://doi.org/10.1101/2024.07.12.603349

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