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Image‐based assessment of microvascular function and structure in collagen XV‐ and XVIII‐deficient mice
Author(s) -
Rygh C. B.,
Løkka G.,
Heljasvaara R.,
Taxt T.,
Pavlin T.,
Sormunen R.,
Pihlajaniemi T.,
Curry F. R.,
Tenstad O.,
Reed R. K.
Publication year - 2014
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2013.263574
Subject(s) - basement membrane , connective tissue , perfusion , permeability (electromagnetism) , chemistry , blood flow , extracellular matrix , vascular permeability , pathology , magnetic resonance imaging , anatomy , medicine , membrane , biochemistry , radiology
Key points Collagen XV and XVIII occur in muscle and connective tissue capillaries and are needed for maintaining a normal circulatory phenotype. Lack of collagen XV in mice leads to increased vascular permeability, increased extraction fraction, and increased extravascular extracellular space in striated muscle. Lack of collagen XVIII in mice leads to increased blood flow, permeability, permeability–surface area product and blood–tissue transvascular transfer in striated muscle tissue. Our results show that functional imaging with MRI and subsequent data analysis provide reliable and robust data and are valuable tools for assessing detailed physiological information non‐invasively.Abstract Collagen XV and XVIII are ubiquitous constituents of basement membranes. We aimed to study the physiological roles of these two components of the permeability barrier non‐invasively in striated muscle in mice deficient in collagen XV or XVIII by dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI). Structural information was obtained with transmission electron microscopy (TEM). MR data were analysed by two different analysis methods to quantify tissue perfusion and microcirculatory exchange parameters to rule out data analysis method‐dependent results. Control mice (C57BL/6J Ola/Hsd strain) or mice lacking either collagen XV ( Col15a1 −/− ) or XVIII ( Col18a1 −/− ) were included in the study. MR images were acquired using a preclinical system using gadodiamide (Gd‐DTPA‐BMA, molecular weight 0.58 kDa) as a tracer. Exchange capacity (permeability ( P )–surface area ( S ) product relative to blood flow ( F B )) was increased in test mice compared to controls, but the contributions from P , S , and F B were different in these two phenotypes. F B was significantly increased in Col18a1 −/− , but slightly decreased in Col15a1 −/− . PS was significantly increased only in Col18a1 −/− even though P was increased in both phenotypes suggesting S might also be reduced in Col15a1 −/− mice. Immunohistochemistry and electron microscopy demonstrated alterations in capillary density and morphology in both knockout mouse strains in comparison to the control mice. Both collagen XV and XVIII are important for maintaining normal capillary permeability in the striated muscle. DCE‐MRI and the perfusion analyses successfully determined microvascular haemodynamic parameters of genetically modified mice and gave results consistent with more invasive methods.