Conference Paper

Investigating the role of CD11b/ITGAM, a leukocyte adhesion protein, in cardiac regeneration

Potts, H., Stockdale, W.T., Choudhury, R.P. and Mommersteeg, M.T.M.

Record Number:
4299
Year:
2019
Abstract:
The human heart cannot regenerate following myocardial infarction and instead forms a fibrotic scar that impairs cardiac function. This often leads to heart failure, which is incurable and a major cause of morbidity. Research in the field of cardiac regeneration aims to address this unmet clinical need by stimulating the adult human heart to repair itself, as witnessed in other organisms, like the zebrafish. The Astyanax mexicanus is a uniquely suited model to study cardiac regeneration as it comprises two closely related populations: (1) ‘regenerative’ surface (SF) populations that efficiently replace lost cardiac tissue after injury and (2) the ‘non-regenerative’ Pachόn (PF) cave population that form a scar. Quantitative Trait Locus analysis of the A. mexicanus has identified ITGAM/CD11b as a potential key regulator of cardiac regeneration. ITGAM/CD11b is a leukocyte surface protein that plays an important role in wound repair: it binds to inflamed endothelium to recruit leukocytes to the site of injury so they can clear up debris and coordinate repair and regeneration. RNA sequencing analysis of PF and SF has revealed a number of SNPs in the coding region of ITGAM/CD11b resulting in 2 different proteins, whilst qPCR data shows that PF significantly upregulate ITGAM/CD11b following injury (4-fold increase relative to SF, p<0.005). We thus hypothesised that PF and SF leukocytes bind differently to the endothelium, altering leukocyte recruitment to the wound. Using antibodies and RNAscope, we found striking differences in the spatiotemporal patterns of leukocyte influx at 1 and 3 days following injury. Future studies using flow cytometry will quantify our observations and define the leukocyte subsets that are most impacted by ITGAM/CD11b changes. Understanding how the innate immune responses differ between successful regeneration (SF) and scarring (PF) would be a significant step towards identifying novel therapeutic targets for immunomodulation in heart attack patients.
Times Cited:
1
Conference Name:
Astyanax Interrnational Meeting
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(2017)Lyon, A., Powers, A. K., Gross, J. B. and O'Quin, K. E. (2017)Pierre, C (2017)Gross, J. B. (2017)Riddle, M (2017)Kaplan, S.A., Powers, A.K. and Gross, J.B. (2017)Powers, A.K., Kaplan, S.A., Boggs, T.E. and Gross, J. (2018)Sovrano, V.A., Potrich, D., Foà, A. and Bertolucci, C. (2018)Tang, J.L.Y., Guo, Y., Stockdale, W.T., Rana, K., Killen, A.C., Mommersteeg, M.T.M. and Yamamoto, Y. (2018)Carlson, B.M. and Gross, J.B. (2018)Stockdale, W.T., Lemieux, M.E., Killen, A.C., Zhao, J., Hu, J., Riepsaame, J. Hamilton, N., Kudoh, T., Riley, P.R., van Aerle, R., Yamamoto, Y. and Mommersteeg, M.T.M. (2018)Espinasa, L. (2018)Sears, C.R. and Gross, J.B. (2018)Espinasa, L., Legendre, L., Fumey, J., Blin, M., Rétaux, S. and Espinasa, M. (2018)Stah, B.A., Sears, C.R., Ma, L., Perkins, M. and Gross, J.B. (2018)Mirande, J.M. (2018)Powers, A.K., Boggs, T.E. and Gross, J.B. (2018)Borowsky, R. (2018)Tabin, J.A., Aspiras, A., Martineau, B., Riddle, M., Kowalko, J. Borowsky, R. 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(2018)Torres-Paz,J., Hyacinthe, C., Pierre, C., Retaux, S. (2018)Gore, A.V., Tomins K.A., Iben, J., Ma, L., Castranova, D., Davis, A.E., Parkhurst, A., Jeffery, W.R. and Weinstein, B.M. (2018)Chin, J.S.R., Gassant, C.E., Amaral, P.M., Lloyd, E., Stahl, B.A., Jaggard, J.B., Keene, A.C. and Duboue, E.R. (2018)Gore, A., Jeffery, W., Retaux, S. and Rohner, N. (2018)Gore, A.V., Rohner, N., Rétaux, S. and Jeffery, W.R. (2018)Stern, D.B and Crandall, K.A. (2018)Ma, L., Strickler, A.G., Parkhurst, A., Yoshizawa, M., Shi, J. and Jeffery, W.R. (2018)Alie, A., Devos, L., Torres-Paz, J., Prunier, L., Boulet, F., Blin, M., Elipot, Y. and Retaux, S. (2018)Xiong, S., Krishnan, J., Peuß, F. and Rohner, N. (2018)Ren, X.Y., Hamilton, N., Müller, F. and Yamamoto, Y. (2018)Carlson, B.M., Klingler, I.B., Meyer, B.J. and Gross, J.B. (2018)Torres-Dowdall, J., Karagic, N., Plath, M. and Riesch, R. (2018)Klaassen, H., Wang, Y., Adamski, K., Rohner, N. and Kowalko, J.E. (2018)Elliott, W.R. (2018)Rohner, N. (2018)Devitsina, G.V. and Golovkina, T.V. (2018)Fumey, J., Hinaux, H., Noirot, C., Thermes, C., Rétaux, S. and Casane, D. (2018)Frøland Steindal, I.V., Beale, A.D., Yamamoto, Y. and Whitmore, D. (2018)Gross, J.B., Weagley, J., Stahl, B.A., Ma, L., Espinasa, L. and McGaugh, S.E. (2018)Devi, A., Atukorala, S. and Franz-Odendaal, T.A. (2018)Shiriagin, V. and Korsching, S.I. (2018)Retaux, S. (2018)Blin, M., Tine, E., Meister, L., Elipot, Y., Bibliowicz, J., Espinasa, L. and Rétaux, S. (2018)Bussotti, S., Di Franco, Antonio AU - Bianchi, Carlo Nike AU - Chevaldonné, Pierre AU - Egea, Lea AU - Fanelli, Emanuela AU - Lejeusne, Christophe AU - Musco, Luigi AU - Navarro-Barranco, Carlos AU - Pey, Alexis AU - Planes, Serge AU - (2018)Ornelas-García, P,. Pajares, S., Sosa-Jiménez, V.M., Rétaux, S. and Miranda-Gamboa, R.A. (2018)Potts, H., Stockdale, W.T., Choudhury, R.P. and Mommersteeg, M.T.M. (2019)Gil-Galvez, A., de la Calle Mustienes, E., Neto, A.., Bilandžija, H., Jeffery, W.R., Gómez-Skarmeta, J.L. (2019)Stockdale, W.T., Tang, J.L.Y., Hu, Z., Potts, H., Lemieux, M.E., Yamamoto, Y. and Mommersteeg, M.T.M. (2019)Powers, A.K., Boggs, T.E., Kaplan, S.A., Davis, E.M. and Gross, J.B. (2019)Policarpo, M., Fumey, J., Lafargeas, P., Legendre, L., Naquin, D., Thermes, C., Møller, P.R., Bernatchez, L., García-Machado, E., Rétaux, S. and Casane, D. (2019)Hyacinthe, C., Attia, J. and Retaux, S. (2019)Agnès, F., Devos, L. and Rétaux, S. (2019)Rétaux, S., Bibliowicz, Y., Blin, M., Elipot, Y., Espinasa, L., Hinaux, H. and Tine, E. (2019)Pennisi, E. (2019)Fernández, A.A., Evans, E.I. and Baumann, D.P. (2019)Worsham, M., Fang, J. and Yoshizawa, M. (2019)Blin, M., Fumey, J., Père, S., Pierre, C., Torres-Paz, J., Simon, V., Espinasa, L. Legendre, L., Casane, D. and Rétaux, S. (2019)Ma, L. and Jeffery, W.R. (2019)Duboue, E. (2019)Boggs, T.E. and Gross, J.B. (2019)Garduño-Sánchez, M.A.A. and Ornelas-García, C.P. (2019)Peuß, R., Box, A.C., Wang, Y., Chen, S., Krishnan, J., Tsuchiya, D., Peak, A., Perera, A., Slaughter, B. and Rohner, N. (2019)Stahl, B.A., Peuß, R., McDole, B., Kenzior, A., Jaggard, J.B., Gaudenz, K., Krishnan, J., McGaugh, S.E., Duboue, E.R., Keene, A.C and Rohner, N. (2019)Yoshizawa, M., Valdez, C., Balaan, C., Lactaoen, K., Kato, J., Ito, M., Yew, J. and Iwashita, M. (2019)Hernández, J., Garita-Alvarado, C.A. and Ornelas-García, C.P. (2019)Espinasa, L., Retaux, S., Yoshisawa, M., Heintz, C. and Balogh- Robinson, R. (2019)Stahl, B.A., Peuß, R., McDole, B., Kenzior, A., Jaggard, J.B., Gaudenz, K., Krishnan, J., McGaugh, S.E., Duboue, E.R., Keene, A.C. and Rohner, N. (2019)Gluesenkamp, A. and McGaugh, S. (2019)Kindl, G.H. and O’Quin, K.E. (2019)Stockdale, W.T., Deal, O., Heintz, C., Rohner, N., and Mommersteeg, M.T.M. (2019)Blin, M. and Retaux, S. (2019)Gore, A., Swearer, A., Iben, J. and Weinstein, B. (2019)Chin, J.S.R., Loomis, C.L., Phan, T.A.N., Albert, L.T., Chang, L.P., Keene, A.C. and Duboué, E.R. (2019)Keene, A.C. (2019)Hu, Z., Lemieux, M. and Mommersteeg, M. (2019)Borowsky, R. (2019)Warren, W.C., Koren, S., Meyer, A. and Rohner, N. (2019)Luc, H., Sears, C., Raczka, A. and Gross, J.B. (2019)Leclercq, J., Torres-Paz, J. and Rétaux, S. (2019)McGaugh, S.E., Passow, C., Jaggard, J.B., Stahl, B. and Keene, A. (2019)Wilkens, H (2019)Legendre, L., Pere, S. and Rétaux, S. (2019)Devos, L., Edouard, J., Simon, V., Agnès, F., Sohm, F. and Rétaux, S. (2019)Legendre, L., Guillet, B., Leguay, E., Meunier, E., Keck, N. and Sohm, F. (2019)Fernandes, V.F.L., Hernandez, H., Doeden, N. and Yoshizawa, M. (2019)Jaggard, J., Lloyd, E., Loomis, C., Cook, C., Vega, P., McGaugh, S., Rohner, N., Bohrner, J., Duboue, E. and Keene, A.C. (2019)O’Gorman, M., Lewis, P., Keene, A., Kowalko, J. and Duboué, E. (2019)Atukorallaya, D., Bhatia, V. and Ratnayake, R. (2019)Riddle, M., Damen, F., Aspiras, A., Tabin, J., McGaugh, S. and Tabin, C. (2019)Lloyd, E., Olive, C., Stahl, B.A., Jaggard, J.B., Amaral, P., Duboué, E.R. and Keene, A.C. (2019)Loomis, C., Peuss, R., Green, M., McGaugh, S.E., Rohner, N., Keene, A.C. and Duboue, E.R. (2019)Kowalko, J.E. (2019)McDole, B., Jaggard, J., Duboue, E. and Keene, A.C. (2019)Torres-Paz, J., Leclercq. J. and Rétaux, S. (2019)Bilandžija, H., Hollifield, B., Steck, M., Meng, G., Ng, M., Bedek, J., Ćetković, H., Porter, M., Renner, K.J. ands Jeffery, W.R. (2019)Paz, A., McDole, B., Duboue, E. and Keene, A.C. (2019)Krishnan, J. and Rohner, N. (2019)Imarazene, B., Herpin, A., Feron, R., Postlethwait, J.H., Schartl, M., Retaux, S. and Guiguen, Y. (2019)van der Weele, C.M. and Jeffery, W.R. (2019)Phelps, A. and Gross, J. (2019)Ornelas-García, C.P., Pajares, S., Sosa-Jiménez, V.M., Rétaux, S. and Gamboa-Miranda, R. (2019)Sifuentes-Romero I. and Kowalko, J.E. (2019)Palluzzi, T., Rowland, R. and Gross, J. (2019)Mogdans, J. (2019)Jeffery, W.R., Ma, L., Shi, J., Ng, M. and Gore,A. (2019)Stahl, B.A., Jaggard, J.B., Chin, J.S., Kowalko, J.E., Keene, A.C. and Duboué, E.R. (2019)Powers, A.K., Garita-Alvarado, C., Rodiles, R., Berning, D.J., Gross, J.B. and Ornelas-García, C.P. (2019)Worsham M1, Fernandes, V.F.L., Settle, A., Balaan, C., Lactaoen, K., Tuttle, L.J., Iwashita, M. and Yoshizawa, M.. (2019)Pierre, C., Torres-Paz, J., Froc, C., Callebert, J. and Rétaux, S. (2019)Xiong, S., Krishnan, J., Peuss, R. and Rohner, N. (2019)Peuß, R., Zakibe, Z., Krishnan, J., Merryman, M.S., Baumann, D.P. and Rohner, N. (2019)