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Cigarette Smoke Exacerbates Ventricular Remodeling and Dysfunction in the Volume Overloaded Heart

  • Jessica M. Bradley (a1), Jonathan B. Nguyen (a1), Alyssa C. Fournett (a1) and Jason D. Gardner (a1)

Abstract

Cigarette smoking is an independent risk factor for heart disease and is linked to sudden cardiac death. In this study, we examined the effects of cigarette smoke (CS) on the volume overload stressed heart. Our hypothesis was that CS exacerbates volume overload (VO)–induced cardiac dysfunction by accelerating ventricular remodeling. VO stress was surgically induced in male Sprague-Dawley rats by abdominal aortocaval fistula (ACF). Rats, with and without ACF, were exposed to either room air or CS (6 cigarettes/day) for 6 weeks. Temporal echocardiogram measurements indicated that CS significantly increased VO-induced left ventricular dilatation, prevented compensatory wall thickening, and depressed fractional shortening. Morphological analysis of ventricular collagen revealed that CS blunted compensatory collagen expression (45% decrease versus ACF alone). CS exacerbated the VO-induced increase of MMP-9 and TIMP-1 expression in the heart. CS also blocked the compensatory increases of HIF-1α, VEGF, and TGF-β in the VO-stressed heart. These data indicate that CS worsens VO remodeling by disrupting compensatory mechanisms, thereby promoting eccentric dilation and dysfunction.

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Corresponding author

Corresponding author. E-mail: jgardn@lsuhsc.edu

References

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Adachi, C., Naruse, M., Ishihara, Y., Tanabe, A., Takagi, S., Yoshimoto, T., Naruse, K., Kagawa, J. & Takano, K. (2000). Effects of acute and chronic cigarette smoking on the expression of endothelin-1 mRNA of the cardiovascular tissue in rats. J Cardiovasc Pharm 36, S198S200.
Ambrose, J.A. & Barua, R.S. (2004). The pathophysiology of cigarette smoking and cardiovascular disease. J Am Coll Cardiol 43(10), 17311737.
Azzalini, L., Ferrer, E., Ramalho, L.N., Moreno, M., Domínguez, M., Colmenero, J., Peinado, V.I., Barberà, J.A., Arroyo, V., Ginès, P., Caballería, J. & Bataller, R. (2010). Cigarette smoking exacerbates nonalcoholic fatty liver disease in obese rats. Hepatology 51(5), 15671576.
Brown, L.A., Nunez, D.J., Brookes, C.I.O. & Wilkins, M.R. (1995). Selective increase in endothelin-1 and endothelin A receptor subtype in the hypertrophied myocardium of the aotro-venacaval fistula rat. Cardiovasc Res 29(6), 768774.
Castardeli, E., Duarte, D.R., Minicucci, M.F., Azevedo, P.S., Matsubara, B.B., Matsubara, L.S., Campana, A.O., Paiva, S.A.R. & Zornoff, L.A.M. (2007). Tobacco smoke-induced left ventricular remodeling is not associated with metalloporteinase-2 of -9 activation. Eur J Heart Fail 9, 10811085.
Castardeli, E., Paiva, S.A.R., Matsubara, B.B., Matsubara, L.S., Minicucci, M.F., Azevedo, P.S., Campana, A.O. & Zornoff, L.A.M. (2005). Chronic cigarette smoke exposure results in cardiac remodeling and impaired ventricular function in rats. Arq Bras Cardiol 84(4), 320324.
Chen, L.-J., Zhao, Y., Gao, S., Chou, I.-N., Toselli, P., Stone, P. & Li, W. (2004). Downregulation of lysyl oxidase and upregulation of cellular thiols in rat fetal lung fibroblasts treated with cigarette smoke condensate. Toxicol Sci 83, 372379.
Edirisinghe, I., Arunachalam, G., Wong, C., Yao, H., Rahman, A., Phipps, R.P., Jin, Z.-G. & Rahman, I. (2010). Cigarette smoke-induced oxidative/nitrosative stress impairs VEGF- and fluid shear stress-mediated signaling in endothelial cells. Andioxid Redox Signal 12(12), 13551369.
Edirisinghe, I. & Rahman, I. (2010). Cigarette smoke-mediated oxidative stress, shear stress, and endothelial dysfunction: Role of VEGFR 2. Ann NY Acad Sci 1203, 6672.
Frantz, S., Hu, K., Adamek, A., Wolf, J., Sallam, A., Kg Maier, S., Lonning, S., Ling, H., Ertl, G. & Bauersachs, J. (2008). Transforming growth factor beta inhibition increases mortality and left ventricular dilatation after myocardial infarction. Basic Res Cardiol 103(5), 485492.
Gao, S., Chen, K., Zhao, Y., Rich, C.B., Chen, L., Li, S.J., Toselli, P., Stone, P. & Li, W. (2005). Transcriptional and posttranscriptional inhibition of lysyl oxidase expression by cigarette smoke condensate in cultured rat fetal lung fibroblasts. Toxicol Sci 87(1), 197203.
Gardner, J.D., Brower, G.L. & Janicki, J.S. (2005). Effects of dietary phytoestrogens on cardiac remodeling secondary to chronic volume overload in femal rats. J Appl Physiol 99, 13781383.
Griffith, R. & Standafer, S. (1985). Simultaneous mainstream-sidestream smoke exposure systems II. The rat exposure system. Toxicology 35(1), 1324.
Gu, L., Pandey, V., Greenen, D.L., Chowdhury, S.A.K. & Piano, M.R. (2008). Cigarette smoke-induced left ventricular remodeling is associated with activation of mitrogen-activated protein kinases. Eur J Heart Fail 10, 10571064.
Gunja-Smith, Z., Morales, A.R., Romanelli, R. & Woessner, J.F.W. Jr. (1996). Remodeling of human myocardial collagen in idiopathic dilated cardiomyopathy: Role of metalloproteinases and pyridinoline cross-links. Am J Pathol 148(5), 16391648.
Haak, T., Jungmann, E., Raab, C. & Usadel, K.H. (1994). Elevated endothelin-1 levels after cigarette smoking. Metabolism 43(3), 267269.
Hansson, J., Vasan, R.S., Arnlov, J., Ingelsson, E., Lind, L., Larsson, A., Michaelsson, K. & Sundstrom, J. (2011). Biomarkers of extracellular matrix metabolism (MMP-9 and TIMP-1) and risk of stroke, myocardial infarction, and cause-specific mortality: Cohort study. PLoS One 6(1), e16185.
Higgins, D.F., Biju, M.P., Akai, Y., Wutz, A., Johnson, R.S. & Haase, V.H. (2004). Hypoxic induction of Ctgf is directly mediated by Hif-1. Am J Physiol-Renal 287(6), F1223F1232.
Hutchinson, K.R., Stewart, J.A. Jr. & Lucchesi, P.A. (2010). Extracellular matrix remodeling during the progression of volume overload-induced heart failure. J Molec Cell Cardiol 48, 564569.
Izumiya, Y., Shiojima, I., Sato, K., Sawyer, D., Colucci, W. & Walsh, K. (2006). Vascular endothelin growth factor blockade promotes the transition from compensatory cardiac hypertrophy to failure in response to pressure overload. Hypertension 47, 887893.
Jorgensen, L.N., Kallehave, F., Christensen, E., Siana, J.E. & Gottrup, F. (1998). Less collagen production in smokers. Surgery 123(4), 450455.
Jourdan-LeSaux, C., Zhang, J. & Lindsey, M.L. (2010). Extracellular matrix roles during cardiac repair. Life Sci 87, 391400.
Knuutinen, A., Kokkonen, N., Risteli, J., Vahakangas, K., Kallioinen, M., Salo, T., Sorsa, T. & Oikarinen, A. (2002). Smoking affects collagen synthesis and extracellular matrix turnover in human skin British. J Dermatol 146, 588594.
Lim, H. & Zhu, Y.Z. (2006). Role of transforming growth factor-B in the progression of heart failure. Cell Mol Life Sci 63, 25842596.
Lu, Y., Azad, N., Wang, L., Iyer, A.K.V., Castranova, V., Jiang, B.-H. & Rojanasakul, Y. (2010). Phosphatidylinositol-3-kinase/Akt regulates bleomycin-induced fibroblast proliferation and collagen production. Am J Respir Cell Mol Biol 42, 432441.
Lucas, J.A., Zhang, Y., Li, P., Gong, K., Miller, A.P., Hassan, E., Hage, F., Xing, D., Wells, B., Oparil, S. & Chen, Y.-F. (2010). Inhibition of transforming growth factor-B signaling induces left ventricular dilation and dysfunction in the pressure overload heart. Am J Physiol Heart Circ Physiol 298, H424H432.
Margulies, K., Hildebrand, F., Lerman, A., Perrella, M. & Burnett, J. Jr. (1990). Increased endothelin in experimental heart failure. Circulation 82, 22262230.
McMurray, J., Ray, S., Abdullah, I., Dargie, H. & Morton, J. (1992). Plasma endothelin in chronic heart failure. Circulation 85, 13741379.
Michaud, S.E., Ménard, C., Guy, L.G., Gennaro, G. & Rivard, A. (2003). Inhibition of hypoxia-induced angiogenesis by cigarette smoke exposure: Impairment of the HIF-1alpha/VEGF pathway. FASEB J 17(9), 11501152.
Morimoto, Y., Tsuda, T., Nakamura, H., Hori, H., Yamato, H., Nagata, N., Higashi, T., Kido, M. & Tanaka, I. (1997). Expression of matrix metalloproteinases, tissue inhibitiors of metalloproteinases, and extracellular matrix mRNA following exposure to mineral fibers and cigarette smoke in vivo. Exp Health Persp 105, 12471251.
Pauschinger, M., Knof, D., Petschauer, S., Doerner, A., Poller, W., Schwimmbeck, P.L., Kuhl, U. & Schultheiss, H.-P. (1999). Dilated cardiomyopathy is associated with significant changes in collagen type I/III. Circulation 99, 27502756.
Raveendran, M., Senthil, D., Utama, B., Shen, Y., Dudley, D., Wang, J., Zhang, Y. & Wang, X.L. (2004). Cigarette suppresses the expression of P4Ha and vascular collagen production. BBRC 323, 592598.
Rudnicki, M., Perco, P., Enrich, J., Eder, S., Heininger, D., Bernthaler, A., Wiesinger, M., Sarkozi, R., Noppert, S.-J., Schramek, H., Mayer, B., Oberbauer, R. & Mayer, G. (2009). Hypoxia response and VEGF—A expression in human proximal tubular epithelial cells in stable and progressive renal disease. Lab Invest 89(3), 337346.
Shiojima, I., Sato, K., Izumiya, Y., Schiekofer, S., Ito, M., Liao, R. & Colucci, W. (2005). Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failuer. J Clin Invest 58, 2637.
Spain, D.M. & Bradess, V.A. (1970). Sudden death from coronary heart disease: Survival time, frequency of thrombi, and cigarette smoking. Chest 58, 107110.
Spinale, F.G., Coker, M.L., Thomas, C.V., Walker, J.D., Mukherjee, R. & Hebbar, L. (1998). Time-dependent changes in matrix metalloproteinase activity and expression during the progression of congesitve heart failure: Relation to ventricular and myocyte function. Circ Res 82, 482495.
Spinella, F., Rosano, L., Castro, V.D., Natalis, P.G. & Bagnato, A. (2002). Endothelin-1 induces vascular endothelial growth factor by increasing hypoxia-inducible factor-1a in ovarian carcinoma cells. J Biol Chem 277, 2785027855.
Thackaberry, E.A., Gabaldon, D.M., Walker, M.K. & Smith, S.M. (2002). Aryl hydrocarbon receptor null mice develop cardiac hypertrophy and increased hypoxia-inducible factor-1 a in the absence of cardiac hypoxia. Cardiovasc Toxicol 2, 263273.
Villarreal, F.J. & Dillmann, W.H. (1992). Cardiac hypertrophy-induced changes in mRNA levles for TGF-B1, fibronectin, and collagen. Am J Physiol Heart Circ Physiol 262, H1861H1866.
Villarreal, F.J., Hong, D. & Omens, J. (1999). Nicotine-modified postinfarction left ventricular remodeling. Am J Physiol Heart Circ Physiol 276, H1103H1106.
Voloshenyuk, T.G. & Gardner, J.D. (2010). Estrogen improves TIMP-MMP balance and collagen distribution in volume-overloaded hearts of ovariectomized females. Am J Physiol Regul Integr Comp Physiol 299, R686R693.
Voloshenyuk, T.G., Landesman, E.S., Khoutorova, E., Hart, A.D. & Gardner, J.D. (2011). Induction of cardiac fibroblast lysyl oxidase by TGF-[beta]1 requires PI3K/Akt, Smad3, and MAPK signaling. Cytokine 55(1), 9097.
Weber, K.T. (1997). Extracellular matrix remodeling in heart failure. Circulation 96, 40654082.
Zentilin, L., Puligadda, U., Lionetti, V., Zacchigna, S., Collesi, C., Pattarini, L., Ruozi, G., Camporesi, S., Sinagra, G., Pepe, M., Recchia, F.A. & Giacca, M. (2010). Cardiomyocyte VEGFR-1 activation by VEGF-B induces compensatory hypertrophy and preserves cardiac function after myocardial infarction FASEB J 24(5), 14671478.
Zhu, B., Sun, Y., Sievers, R., Glantz, S., Parmley, W. & Wolfe, C. (1994). Exposure to environmental tobacco smoke increased myocardial infarct size in rats. Circulation 89, 12821290.
Zornoff, L.A., Matsubara, B.B., Matsubara, L.S., Mincucci, M.F., Azevedo, P.S., Campanha, A.O. & Paiva, S.A.R. (2006). Cigarette smoke exposure intensifies ventricular remodeling process following myocardial infarction. Arq Bras Cardiol 86(4), 276281.

Keywords

Cigarette Smoke Exacerbates Ventricular Remodeling and Dysfunction in the Volume Overloaded Heart

  • Jessica M. Bradley (a1), Jonathan B. Nguyen (a1), Alyssa C. Fournett (a1) and Jason D. Gardner (a1)

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