Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-22T22:55:01.577Z Has data issue: false hasContentIssue false
  • English
  • Français

The Role of Interleukin-6 in the Formation of the Coronary Vasculature

Published online by Cambridge University Press:  27 August 2009

Indroneal Banerjee ,
John W. Fuseler ,
Colby A. Souders ,
Stephanie L.K. Bowers  and
Troy A. Baudino
Indroneal Banerjee
Affiliation:
University of South Carolina School of Medicine, Cell and Developmental Biology and Anatomy, 6439 Garners Ferry Rd., Columbia, SC 29209, USA
John W. Fuseler
Affiliation:
University of South Carolina School of Medicine, Cell and Developmental Biology and Anatomy, 6439 Garners Ferry Rd., Columbia, SC 29209, USA
Colby A. Souders
Affiliation:
University of South Carolina School of Medicine, Cell and Developmental Biology and Anatomy, 6439 Garners Ferry Rd., Columbia, SC 29209, USA
Stephanie L.K. Bowers
Affiliation:
University of South Carolina School of Medicine, Cell and Developmental Biology and Anatomy, 6439 Garners Ferry Rd., Columbia, SC 29209, USA
Troy A. Baudino*
Affiliation:
University of South Carolina School of Medicine, Cell and Developmental Biology and Anatomy, 6439 Garners Ferry Rd., Columbia, SC 29209, USA
*
Corresponding author. E-mail: [email protected]
Get access

Abstract

The formation and the patterning of the coronary vasculature are critical to the development and pathology of the heart. Alterations in cytokine signaling and biomechanical load can alter the vascular distribution of the vessels within the heart. Changes in the physical patterning of the vasculature can have significant impacts on the relationships of the pressure-flow network and distribution of critical growth and survival factors to the tissue. Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates several biological processes, including vasculogenesis. Using both immunohistological and cardioangiographic analyses, we tested the hypothesis that IL-6-loss will result in decreased vessel density, along with changes in vascular distribution. Moreover, given the impact of vascular patterning on pressure-flow and distribution mechanics, we utilized non-Euclidean geometrical fractal analysis to quantify the changes in patterning resulting from IL-6-loss. Our analyses revealed that IL-6-loss results in a decreased capillary density and increase in intercapillary distances, but does not alter vessel size or diameter. We also observed that the IL-6−/− coronary vasculature had a marked increase in fractal dimension (D value), indicating that IL-6-loss alters vascular patterning. Characterization of IL-6-loss on coronary vasculature may lend insight into the role of IL-6 in the formation and patterning of the vascular bed.

Keywords

fractal geometrycoronary vasculatureimage analysesInterleukin-6
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 15 , Issue 5 , October 2009 , pp. 415 - 421
Copyright
Copyright © Microscopy Society of America 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Adachi, Y., Aoki, C., Yoshio-Hoshino, N., Takayama, K., Curiel, D.T. & Nishimoto, N. (2006). Interleukin-6 induces both cell growth and VEGF production in malignant mesotheliomas. Int J Cancer 119(6), 1303–1311.CrossRefGoogle ScholarPubMed
Anderson, J.C., Babb, A.L. & Hlastala, M.P. (2005). A fractal analysis of radial distribution of bronchial capillaries around large airways. J Appl Physiol 98, 850–855.CrossRefGoogle ScholarPubMed
Baumgarten, G., Knuefermann, P., Kalra, D., Gao, F., Taffet, G.E., Michael, L., Blackshear, P.J., Carballo, E., Sivasubramanian, N. & Mann, D.L. (2002). Load-dependent and -independent regulation of proinflammatory cytokine and cytokine receptor gene expression in the adult mammalian heart. Circulation 105(18), 2192–2197.CrossRefGoogle ScholarPubMed
Di Ieva, A., Grizzi, F., Gaetani, P., Goglia, U., Tschabitscher, M., Mortini, P. & Baena, R.R.Y. (2008). Euclidean and fractal geometry of microvascular networks in normal and neoplastic pituitary tissue. Neurosurg Rev 31, 271–281.CrossRefGoogle ScholarPubMed
Fernández, E. & Jelinek, H.F. (2001). Use of fractal theory in neuroscience: Methods, advantages, and potential problems. Methods 24(4), 309–321.CrossRefGoogle ScholarPubMed
Feurino, L.W., Zhang, Y., Bharadwaj, U., Zhang, R., Li, F., Fisher, W.E., Brunicardi, F.C., Chen, C., Yao, Q. & Li, M. (2007). IL-6 stimulates Th2 type cytokine secretion and upregulates VEGF and NRP-1 expression in pancreatic cancer cells. Cancer Biol Ther 6(7), 1096–1100.CrossRefGoogle ScholarPubMed
Friehs, I., Barillas, R., Vasilyev, N.V., Roy, N., McGowan, F.X. & del Nido, P.J. (2006a). Vascular endothelial growth factor prevents apoptosis and preserves contractile function in hypertrophied infant heart. Circulation 114(1 Suppl), I290–295.CrossRefGoogle ScholarPubMed
Friehs, I., Margossian, R.E., Moran, A.M., Cao-Danh, H., Moses, M.A. & del Nido, P.J. (2006b). Vascular endothelial growth factor delays onset of failure in pressure-overloaded hypertrophy through matrix metalloproteinase activation and angiogenesis. Basic Res Cardiol 101(3), 204–213.CrossRefGoogle Scholar
Friehs, I., Moran, A.M., Stamm, C., Choi, Y.H., Cowan, D.B., McGowan, F.X. & del Nido, P.J. (2004). Promoting angiogenesis protects severely hypertrophied hearts from ischemic injury. Ann Thorac Surg 77(6), 2004–2010.CrossRefGoogle ScholarPubMed
Fuseler, J.W., Merrill, D.M., Rogers, J.A., Grisham, M.B. & Wolf, R.E. (2006). Analysis and quantitation of NF-kappaB nuclear translocation in tumor necrosis factor alpha (TNF-alpha) activated vascular endothelial cells. Microsc Microanal 12(3), 269–276.CrossRefGoogle ScholarPubMed
Fuseler, J.W., Millette, C.F., Davis, J.M. & Carver, W. (2007). Fractal and image analysis of morphological changes in the actin cytoskeleton of neonatal cardiac fibroblasts in response to mechanincal stretch. Microsc Microanal 13, 133–143.CrossRefGoogle Scholar
Glenny, R.W., Robertson, H.T., Yamashiro, S. & Bassingthwaighte, J.B. (1991). Applications of fractal analysis to physiology. J Appl Physiol 70(6), 2351–2367.CrossRefGoogle ScholarPubMed
Grizzi, F., Russo, C., Colombo, P., Franceschini, B., Frezza, E.E., Cobos, F. & Chiriva-Internati, M. (2005). Quantitative evaluation and modeling of two-dimensional neovascular network complexity: The surface fractal dimension. BMC Cancer 5, 14–23.Google ScholarPubMed
Hilfiker-Kleiner, D., Hilfiker, A., Fuchs, M., Kaminski, K., Schaefer, A., Schieffer, B., Hillmer, A., Schmiedl, A., Ding, Z. & Podewski, E. (2004). Signal transducer and activator of transcription 3 is required for myocardial capillary growth, control of interstitial matrix deposition and heart protection form ischemic injury. Circ Res 95(2), 187–195.CrossRefGoogle Scholar
Hudlicka, O. & Brown, M. (1996). Postnatal growth of the heart and its blood vessels. J Vasc Res 33(4), 266–287.CrossRefGoogle ScholarPubMed
Hudlicka, O., Brown, M. & Egginton, S. (1992). Angiogenesis in skeletal and cardiac muscle. Physiol Rev 72, 369–417.CrossRefGoogle ScholarPubMed
Izumiya, Y., Shiojima, I., Sato, K., Sawyer, D.B., Colucci, W.S. & Walsh, K. (2006). Vascular endothelial growth factor blockade promotes the transition from compesatory cardiac hypertrophy to failure in response to pressure overload. Hypertension 47(5), 887–893.CrossRefGoogle ScholarPubMed
Kalliokoski, K.K., Kuusela, T.A., Laaksonen, M.S., Knuuti, J. & Nuutila, P. (2003). Muscle fractal vascular branching pattern and microvascular perfusion heterogeneity in endurance-trained and untrained men. J Physiol 546(Pt2), 529–535.CrossRefGoogle ScholarPubMed
Kamimura, D., Ishihara, K. & Hirano, T. (2003). Il-6 signal transduction and its physiological roles: The signal orchestration model. Rev Physiol Biochem Pharmacol 149, 1–38.Google ScholarPubMed
Karch, R., Neumann, F., Ullrich, R., Neumuller, J., Podesser, B., Neumann, M. & Schreiner, W. (2005). The spatial pattern of coronary capillaries in patients with dilated, ischemic, or inflammatory cardiomyopathy. Cardiovasc Pathol 14(3), 135–144.CrossRefGoogle ScholarPubMed
Kassab, G.S. (2000). The coronary vasculature and its reconstruction. Ann Biomed Eng 28, 903–915.CrossRefGoogle ScholarPubMed
Korecky, B., Hai, C.M. & Rakusan, K. (1982). Functional capilliary density in normal and transplanted rat hearts. Can J Phsiol Pharmocol 60(1), 23–32.CrossRefGoogle Scholar
Kurdi, M. & Booz, G.W. (2007). Can the protective actions of JAK-STAT in the heart be exploited therapeutically? Parsing the regulation of Interleukin-6 type cytokine signaling. J Cardiovasc Pharmacol 50(2), 126–141.CrossRefGoogle ScholarPubMed
Matsushita, K., Iwanaga, S., Oda, T., Kimura, K., Shimada, M., Sano, M., Umezawa, A., Hata, J. & Ogawa, S. (2005). Interleukin-6/soluble Interleukin-6 receptor complex reduces infarct size via inhibiting myocardial apoptosis. Lab Invest 85(10), 1210–1223.CrossRefGoogle ScholarPubMed
NIH (1996). Guide for the Care Use of Laboratory Animals. NIH Publication No. 85-23. Washington, D.C.: U.S. National Institutes of Health.Google Scholar
Rakusan, K. & Korecky, B. (1982). The effects of growth and aging on functional capillary supply of the rat heart. Growth 46(3), 275–281.Google ScholarPubMed
Rega, G., Kaun, C., Demyanets, S., Pfaffenberger, S., Rychli, K., Hohensinner, P.J., Kastl, S.P., Speidl, W.S., Weiss, T.W., Breuss, J.M., Furnkranz, A., Uhrin, P., Zaujec, J., Zilberfarb, V., Frey, M., Roehle, R., Maurer, G., Huber, K. & Wojta, J. (2007). Vascular endothelial growth factor is induced by the inflammatory cytokines interleukin-6 and oncostatin m in human adipose tissue in vitro and in murine adipose tissue in vivo. Arterioscler Thromb Vasc Biol 27(7), 1587–1595.CrossRefGoogle ScholarPubMed
Rogers, J.A. & Fuseler, J.W. (2007). Regulation of NF-kappaB activation and nuclear translocation by exogenous nitric oxide (NO) donors in TNF-alpha activated vascular endothelial cells. Nitric Oxide 16(3), 379–391.CrossRefGoogle ScholarPubMed
Vivanco, F., Martín-Ventura, J.L., Duran, M.C., Barderas, M.G., Blanco-Colio, L., Dardé, V.M., Mas, S., Meilhac, O., Michel, J.B., Tuñón, J. & Egido, J. (2005). Quest for novel cardiovascular biomarkers by proteomic analysis. J Proteome Res 4(4), 1181–1191CrossRefGoogle ScholarPubMed
Walsh, K. & Shiojima, I. (2007). Cardiac growth and angiogenesis coordinated by intertissue interactions. J Clin Invest 117(11), 3176–3179.CrossRefGoogle ScholarPubMed
Zmeskal, O., Nezadal, M. & Sedlak, O. (2001). Využití fraktální analýzy při hodnocení kvality tisku (The usage of fractal analysis for evaluating the quality of print), IV. Polygraphic Conference, pp. 92–101 (Czech version, English abstract included, PDF). Available at http://www.fch.vutbr.cz/lectures/imagesci.Google Scholar