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Pathogenic Origins of Fibrosis in the Hypertensive Heart Disease that Accompanies Aldosteronism

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Cardiac Fibrosis and Heart Failure: Cause or Effect?

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 13))

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Abstract

Cardiac fibrosis interferes with the structural homogeneity of the myocardium in hypertensive heart disease (HHD). Its morphologic presentations include: widely scattered microscopic scars which have replaced myocytes lost to necrosis; and a perivascular fibrosis of intramural coronary arteries. An animal model of aldosterone/salt treatment has been used to examine the pathogenic origins of myocyte necrosis and coronary vasculopathy. A common cellular/subcellular pathway involving parathyroid hormone-mediated, intracellular Ca2+ overload-induced, mitochondrial-derived oxidative stress was identified. Myofibroblasts and their secretome which includes de novo generation of angiotensin peptides, are responsible for fibrogenesis at these sites. Cardioprotection includes upstream prevention of myocyte loss and vascular remodeling or downstream ablation of myofibroblasts and ongoing fibrogenesis at these sites.

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Conflict of Interest

This work was supported, in part, by NIH grants R01HL073043, R01HL090867 and R01HL096813 (KTW). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Division of Cardiovascular Diseases, University of Tennessee Health Science Center, 956 Court Ave., Suite A312, 38163, Memphis, TN, USA

    R. Justin McCullough MD, Yao Sun MD, PhD, Kevin P. Newman MD, Kodangudi B. Ramanathan MD & Dr. Karl T. Weber MD

  2. Department of Microbiology,Immunology & Biochemistry, University of Tennessee Health Science Center, 858 Madison Ave., 101H Molecular Sciences Bldg., Memphis, TN, USA

    Ramareddy V. Guntaka PhD

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  1. R. Justin McCullough MD
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  2. Yao Sun MD, PhD
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  3. Kevin P. Newman MD
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  4. Kodangudi B. Ramanathan MD
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  5. Ramareddy V. Guntaka PhD
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  6. Dr. Karl T. Weber MD
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Correspondence to Karl T. Weber MD .

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Editors and Affiliations

  1. Institute of Cardiovascular Sciences St. Boniface Hospital Research Centre Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Canada

    Ian M.C. Dixon

  2. Institute of Cardiovascular Sciences St. Boniface Hospital Research Centre Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada

    Jeffrey T. Wigle

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McCullough, R., Sun, Y., Newman, K., Ramanathan, K., Guntaka, R., Weber, K. (2015). Pathogenic Origins of Fibrosis in the Hypertensive Heart Disease that Accompanies Aldosteronism. In: Dixon, I., Wigle, J. (eds) Cardiac Fibrosis and Heart Failure: Cause or Effect?. Advances in Biochemistry in Health and Disease, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-319-17437-2_6

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