A Mitochondriocentric pathway to cardiomyocyte necrosis: An upstream molecular mechanism in myocardial fibrosis

Adedayo A. Adeboye, Kevin P. Newman, Dwight Dishmon, Shadwan Alsafwah, Syamal Bhattacharya, Karl Weber

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

The pathophysiologic origins of heart failure can be attributed to a pathologie remodeling of myocardium, including necrotic loss of cardiomyocytes and consequent reparative fibrosis. Hypertensive heart disease with concentric left ventricular hypertrophy and fibrosis represents a major etiologic factor accounting for diastolic heart failure. Herein, we focus on molecular mechanisms to the precursor of fibrosis, namely, cardiomyocyte necrosis, whose pathogenic origin resides in a mitochondriocentric signal-transducer-effector pathway. Its major components include intracellular Ca2+ overloading of cytosolic and mitochondrial domains, the induction of oxidative stress by these organelles which overwhelms endogenous antioxidant defenses, and the increased opening potential of the mitochondrial permeability transition pore. Novel cardioprotective strategies aimed at preventing the progressive remodeling of the failing heart should target upstream molecular mechanisms that prevent cardiomyocyte necrosis rather than downstream events involving collagen turnover related to fibrosis.

Original languageEnglish (US)
Title of host publicationCardiac Remodeling
Subtitle of host publicationMolecular Mechanisms
PublisherSpringer New York
Pages113-125
Number of pages13
ISBN (Electronic)9781461459309
ISBN (Print)9781461459293
DOIs
StatePublished - Jan 1 2013

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Cardiac Myocytes
Fibrosis
Necrosis
Diastolic Heart Failure
Oxidative stress
Left Ventricular Hypertrophy
Transducers
Organelles
Heart Diseases
Myocardium
Oxidative Stress
Collagen
Heart Failure
Antioxidants

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

A Mitochondriocentric pathway to cardiomyocyte necrosis : An upstream molecular mechanism in myocardial fibrosis. / Adeboye, Adedayo A.; Newman, Kevin P.; Dishmon, Dwight; Alsafwah, Shadwan; Bhattacharya, Syamal; Weber, Karl.

Cardiac Remodeling: Molecular Mechanisms. Springer New York, 2013. p. 113-125.

Research output: Chapter in Book/Report/Conference proceedingChapter

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