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Calcium Overloading-Induced Oxidative Stress-Mediated Cellular and Subcellular Remodeling

  • Yaser Cheema
  • Atta U. Shahbaz
  • Syamal K. Bhattacharya
  • Robert A. Ahokas
  • Yao Sun
  • Ivan C. Gerling
  • Karl T. Weber
Chapter

Abstract

A progressive loss of cardiomyocytes contributes to the heart’s failure as a muscular pump. This includes the necrotic death of these cells, which are replaced by fibrous tissue (vis-à-vis apoptotic cell death). In the explanted failing heart, scattered foci of fibrosis are found throughout both ventricles, representing the major component of pathologic remodeling. Further evidence on the importance of cardiomyocyte necrosis relates to elevations in serum troponins, biomarkers of cellular disintegration that appear in patients having congestive heart failure (CHF) in the absence of ischemia–infarction or renal failure. The CHF syndrome has its origins rooted in neurohormonal activation, including the adrenergic nervous and renin–angiotensin–­aldosterone systems, and secondary hyperparathyroidism. Effector hormones, including parathyroid hormone, contribute to cardiomyocyte necrosis based on a mitochondriocentric signal-transducer–effector pathway whose major components include the intracellular Ca2+ overloading-induced, oxidative stress-­mediated opening of the mitochondria inner membrane permeability transition pore. An ensuing loss of ATP and organellar degeneration account for necrotic cell death. Herein, we focus on this pathway, as it relates to various acute and chronic stressor states: isoproterenol treatment, aldosterone–salt treatment, and the cardiomyopathy of the Syrian Hamster. Cumulative insights gathered from these models lead to the inevitable recognition as to the central role of mitochondria in cellular–subcellular remodeling. Toward this end, the efficacy and safety of mitochondria-targeted pharmaceuticals and/or nutriceuticals needs to be determined.

Keywords

Mitochondria Cardiomyocytes Calcium overloading Oxidative stress Neurohormones Parathyroid hormone 

Notes

Acknowledgments

This work was supported, in part, by NIH grants R01-HL73043 and R01-HL90867 (K.T.W.). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The authors have no conflicts of interest to disclose.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Yaser Cheema
    • 1
  • Atta U. Shahbaz
    • 1
  • Syamal K. Bhattacharya
    • 1
  • Robert A. Ahokas
    • 2
  • Yao Sun
    • 1
  • Ivan C. Gerling
    • 3
  • Karl T. Weber
    • 1
  1. 1.Division of Cardiovascular Diseases, Department of MedicineUniversity of Tennessee Health Science CenterMemphisUSA
  2. 2.Department of Obstetrics & GynecologyUniversity of Tennessee Health Science CenterMemphisUSA
  3. 3.Division of Endocrinology, Department of MedicineUniversity of Tennessee Health Science CenterMemphisUSA

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