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Commonly used mouse strains have distinct vascular properties

Abstract

Mice are the most common animal model to investigate human disease and explore physiology. Mice are practical, cost efficient, and easily used for genetic manipulations. Although variability in cardiac structure and function among mouse strains is well noted, the effect of mouse strain on vascular stiffness indices is not known. Here, we compared mouse strain-dependent differences in key vascular stiffness indices among frequently used inbred mouse strains—C57Bl/6J, 129S, and Bl6/129S. In young healthy animals, baseline blood pressure and heart rate were identical in all strains, and independent of gender. However, both active in vivo and passive ex vivo vascular stiffness indices exhibited distinct differences. Specifically, both male and female 129S animals demonstrated the highest tensile stiffness, were least responsive to acetylcholine-induced vasorelaxation, and showed the lowest pulse wave velocity (PWV), an index of in vivo stiffness. C57Bl/6J mice demonstrated the highest PWV, lowest tensile stiffness, and the highest response to acetylcholine-induced vasorelaxation. Interestingly, within each strain, female mice had more compliant aortas. C57Bl/6J mice had thinner vessel walls with fewer layers, whereas 129S mice had the thickest walls with the most layers. Values in the Bl6/129S mixed background mice fell between C57Bl/6J and 129S mice. In conclusion, we show that underlying vascular properties of different inbred wild-type mouse strains are distinct, despite superficial similarities in blood pressure. For each genetic modification, care should be taken to identify proper controls, and conclusions might need to be verified in more than one strain to minimize the risk of false positive studies.

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References

  1. Doevendans PA, Daemen MJ, de Muinck ED, Smits JF. Cardiovascular phenotyping in mice. Cardiovasc Res. 1998;39:34–49.

    Article  CAS  Google Scholar 

  2. Schlager G, Weibust RS. Genetic control of blood pressure in mice. Genetics. 1967;55:497–506.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Barnabei MS, Palpant NJ, Metzger JM. Influence of genetic background on ex vivo and in vivo cardiac function in several commonly used inbred mouse strains. Physiol Genom. 2010;42A:103–13.

    Article  CAS  Google Scholar 

  4. Hoit BD, Kiatchoosakun S, Restivo J, Kirkpatrick D, Olszens K, Shao H, et al. Naturally occurring variation in cardiovascular traits among inbred mouse strains. Genomics. 2002;79:679–85.

    Article  CAS  Google Scholar 

  5. Ryan MJ, Didion SP, Davis DR, Faraci FM, Sigmund CD. Endothelial dysfunction and blood pressure variability in selected inbred mouse strains. Arterioscler Thromb Vasc Biol. 2002;22:42–8.

    Article  CAS  Google Scholar 

  6. Fujii M, Hara H, Meng W, Vonsattel JP, Huang Z, Moskowitz MA. Strain-related differences in susceptibility to transient forebrain ischemia in SV-129 and C57black/6 mice. Stroke. 1997;28:1805–10.

    Article  CAS  Google Scholar 

  7. Di Lazzaro V, Pilato F, Dileone M, Tonali PA, Ziemann U. Dissociated effects of diazepam and lorazepam on short-latency afferent inhibition. J Physiol. 2005;569:315–23.

    Article  Google Scholar 

  8. Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol. 2010;55:1318–27.

    Article  Google Scholar 

  9. Steppan J, Barodka V, Berkowitz DE, Nyhan D. Vascular stiffness and increased pulse pressure in the aging cardiovascular system. Cardiol Res Pract. 2011;2011:263585.

    Article  Google Scholar 

  10. Oh YJ, Pau VC, Steppan J, Sikka G, Bead VR, Nyhan D, et al. Role of tissue transglutaminase in age-associated ventricular stiffness. Amino Acids. 2017;49:695–704.

    Article  CAS  Google Scholar 

  11. Steppan J, Wang H, Bergman Y, Rauer MJ, Tan S, Jandu S, et al. Lysyl oxidase-like 2 depletion is protective in age-associated vascular stiffening. Am J Physiol Heart Circ Physiol. 2019;317:H49–59.

    Article  CAS  Google Scholar 

  12. Steppan J, Sikka G, Jandu S, Barodka V, Halushka MK, Flavahan NA, et al. Exercise, vascular stiffness, and tissue transglutaminase. J Am Heart Assoc. 2014;3:e000599.

    Article  Google Scholar 

  13. Jung SM, Jandu S, Steppan J, Belkin A, An SS, Pak A, et al. Increased tissue transglutaminase activity contributes to central vascular stiffness in eNOS knockout mice. Am J Physiol Heart Circ Physiol. 2013;305:H803–10.

    Article  CAS  Google Scholar 

  14. Steppan J, Bergman Y, Viegas K, Armstrong D, Tan S, Wang H, et al. Tissue transglutaminase modulates vascular stiffness and function through crosslinking-dependent and crosslinking-independent functions. J Am Heart Assoc. 2017;6:2.

    Article  Google Scholar 

  15. Barreto Ortiz S, Hori D, Nomura Y, Yun X, Jiang H, Yong H, et al. Opsin 3 and 4 mediate light-induced pulmonary vasorelaxation that is potentiated by G protein-coupled receptor kinase 2 inhibition. Am J Physiol Lung Cell Mol Physiol. 2018;314:L93–106.

    Article  Google Scholar 

  16. Hori D, Dunkerly-Eyring B, Nomura Y, Biswas D, Steppan J, Henao-Mejia J, et al. miR-181b regulates vascular stiffness age dependently in part by regulating TGF-beta signaling. PLoS ONE. 2017;12:e0174108.

    Article  Google Scholar 

  17. Natarajan N, Hori D, Flavahan S, Steppan J, Flavahan NA, Berkowitz DE, et al. Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41. Physiol Genom. 2016;48:826–34.

    Article  CAS  Google Scholar 

  18. Steppan J, Tran HT, Bead VR, Oh YJ, Sikka G, Bivalacqua TJ, et al. Arginase inhibition reverses endothelial dysfunction, pulmonary hypertension, and vascular stiffness in transgenic sickle cell mice. Anesth Analg. 2016;123:652–8.

    Article  Google Scholar 

  19. Wagenseil JE, Mecham RP. Vascular extracellular matrix and arterial mechanics. Physiol Rev. 2009;89:957–89.

    Article  CAS  Google Scholar 

  20. Zieman SJ, Melenovsky V, Kass DA. Mechanisms, pathophysiology, and therapy of arterial stiffness. Arterioscler Thromb Vasc Biol. 2005;25:932–43.

    Article  CAS  Google Scholar 

  21. Steppan J, Tran H, Benjo AM, Pellakuru L, Barodka V, Ryoo S, et al. Alagebrium in combination with exercise ameliorates age-associated ventricular and vascular stiffness. Exp Gerontol. 2012;47:565–72.

    Article  CAS  Google Scholar 

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Funding

This work was supported by two Stimulating and Advancing ACCM Research (StAAR) grants from the Department of Anesthesiology and Critical Care Medicine at Johns Hopkins University (to LS and JS), a JHU Discovery Award and MedImmune research award (to LS), and a K08 grant (K08HL145132) from the National Heart Lung and Blood Institute (to JS).

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Correspondence to Jochen Steppan.

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Steppan, J., Jandu, S., Wang, H. et al. Commonly used mouse strains have distinct vascular properties. Hypertens Res 43, 1175–1181 (2020). https://doi.org/10.1038/s41440-020-0467-4

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