Image-based assessment of microvascular function and structure in collagen XV- and XVIII-deficient mice

C. B. Rygh, G. Løkka, R. Heljasvaara, T. Taxt, T. Pavlin, R. Sormunen, T. Pihlajaniemi, F. R. Curry, O. Tenstad, R. K. Reed

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 (FB)) was increased in test mice compared to controls, but the contributions from P, S, and FB were different in these two phenotypes. FB 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.

Original languageEnglish (US)
Pages (from-to)325-336
Number of pages12
JournalJournal of Physiology
Volume592
Issue number2
DOIs
StatePublished - Jan 2014

Fingerprint

Collagen Type XVIII
gadodiamide
Striated Muscle
Permeability
Collagen
Phenotype
Magnetic Resonance Angiography
Capillary Permeability
Transmission Electron Microscopy
Inbred C57BL Mouse
Basement Membrane
Knockout Mice
Electron Microscopy
Perfusion
Molecular Weight
Hemodynamics
Immunohistochemistry
Magnetic Resonance Imaging

ASJC Scopus subject areas

  • Physiology

Cite this

Rygh, C. B., Løkka, G., Heljasvaara, R., Taxt, T., Pavlin, T., Sormunen, R., ... Reed, R. K. (2014). Image-based assessment of microvascular function and structure in collagen XV- and XVIII-deficient mice. Journal of Physiology, 592(2), 325-336. https://doi.org/10.1113/jphysiol.2013.263574

Image-based assessment of microvascular function and structure in collagen XV- and XVIII-deficient mice. / Rygh, C. B.; Løkka, G.; Heljasvaara, R.; Taxt, T.; Pavlin, T.; Sormunen, R.; Pihlajaniemi, T.; Curry, F. R.; Tenstad, O.; Reed, R. K.

In: Journal of Physiology, Vol. 592, No. 2, 01.2014, p. 325-336.

Research output: Contribution to journalArticle

Rygh, CB, Løkka, G, Heljasvaara, R, Taxt, T, Pavlin, T, Sormunen, R, Pihlajaniemi, T, Curry, FR, Tenstad, O & Reed, RK 2014, 'Image-based assessment of microvascular function and structure in collagen XV- and XVIII-deficient mice', Journal of Physiology, vol. 592, no. 2, pp. 325-336. https://doi.org/10.1113/jphysiol.2013.263574
Rygh, C. B. ; Løkka, G. ; Heljasvaara, R. ; Taxt, T. ; Pavlin, T. ; Sormunen, R. ; Pihlajaniemi, T. ; Curry, F. R. ; Tenstad, O. ; Reed, R. K. / Image-based assessment of microvascular function and structure in collagen XV- and XVIII-deficient mice. In: Journal of Physiology. 2014 ; Vol. 592, No. 2. pp. 325-336.
@article{bd7f1ce172434064b6506eac12d9597b,
title = "Image-based assessment of microvascular function and structure in collagen XV- and XVIII-deficient mice",
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 (FB)) was increased in test mice compared to controls, but the contributions from P, S, and FB were different in these two phenotypes. FB 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.",
author = "Rygh, {C. B.} and G. L{\o}kka and R. Heljasvaara and T. Taxt and T. Pavlin and R. Sormunen and T. Pihlajaniemi and Curry, {F. R.} and O. Tenstad and Reed, {R. K.}",
year = "2014",
month = "1",
doi = "10.1113/jphysiol.2013.263574",
language = "English (US)",
volume = "592",
pages = "325--336",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Image-based assessment of microvascular function and structure in collagen XV- and XVIII-deficient mice

AU - Rygh, C. B.

AU - Løkka, G.

AU - Heljasvaara, R.

AU - Taxt, T.

AU - Pavlin, T.

AU - Sormunen, R.

AU - Pihlajaniemi, T.

AU - Curry, F. R.

AU - Tenstad, O.

AU - Reed, R. K.

PY - 2014/1

Y1 - 2014/1

N2 - 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 (FB)) was increased in test mice compared to controls, but the contributions from P, S, and FB were different in these two phenotypes. FB 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.

AB - 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 (FB)) was increased in test mice compared to controls, but the contributions from P, S, and FB were different in these two phenotypes. FB 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.

UR - http://www.scopus.com/inward/record.url?scp=84892432089&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84892432089&partnerID=8YFLogxK

U2 - 10.1113/jphysiol.2013.263574

DO - 10.1113/jphysiol.2013.263574

M3 - Article

VL - 592

SP - 325

EP - 336

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 2

ER -