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An Experimental and Computational Systems Approach for Studying How Hemodynamics and Bone Marrow‐Derived Cells Coordinate to Regulate Microvascular Remodeling
Author(s) -
Bajikar Sameer S,
Meisner Joshua K,
Price Richard J
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.974.4
Subject(s) - arteriole , arteriogenesis , hemodynamics , in vivo , microcirculation , blood flow , bone marrow , biomedical engineering , anatomy , chemistry , biology , neuroscience , microbiology and biotechnology , angiogenesis , medicine , pathology , cardiology
Hemodynamics, bone marrow derived cell (BMC) recruitment, and growth factor and chemokine signaling all regulate microvascular remodeling; however, the temporal and spatial coordination of these factors in vivo is poorly understood. Therefore, we are creating experimental and computational systems biology approaches for studying how these factors coordinate in structural remodeling of arteriole networks. We have shown that the dorsal skinfold window chamber (DSFWC) preparation can be used for determining the role of BMCs and chemokine receptors in microvascular remodeling (Nickerson et al., ATVB , 2009). Our new experimental model utilizes a modified mouse DSFWC preparation and a microligation device to occlude single arterioles. Following microligation of a single arcade arteriole, we observed a significant increase in the maximal diameter of “collateral” arterioles circumventing the ligation (65%) compared to “background” arterioles (38%) from day 1 to 7. Measured by microsphere particle imaging velocimetry, collateral arterioles sustained a larger increase in centerline velocity (94%) than background arterioles (36%), showing the experimental model permits observation of collateral vessel remodeling to altered blood flow. Next, a computational network model was developed to characterize network‐wide hemodynamic alterations from microligations. The computer model predicted blood flow increases along the determined “collateral” arteriole pathways and other vessels, which correlated with increases in diameter in vivo from day 1 to 7. These new experimental and computational tools will enable us to test how microvascular remodeling is coordinated through altered hemodynamics and BMC recruitment with high spatio‐temporal resolution. Supported by NIH HL74082.