title: Cardiac remodeling and subcellular defects in heart failure due to myocardial infarction and aging.
abstract: Although several risk factors including hypertension, cardiac hypertrophy, coronary artery disease, and diabetes are known to result in heart failure, elderly subjects are more susceptible to myocardial infarction and more likely to develop heart failure. This article is intended to discuss that cardiac dysfunction in hearts failing due to myocardial infarction and aging is associated with cardiac remodeling and defects in the subcellular organelles such as sarcolemma (SL), sarcoplasmic reticulum (SR), and myofibrils. Despite some differences in the pattern of heart failure due to myocardial infarction and aging with respect to their etiology and sequence of events, evidence has been presented to show that subcellular remodeling plays a critical role in the occurrence of intracellular Ca(2+)-overload and development of cardiac dysfunction in both types of failing heart. In particular, alterations in gene expression for SL and SR proteins induce Ca(2+)-handling abnormalities in cardiomyocytes, whereas those for myofibrillar proteins impair the interaction of Ca(2+) with myofibrils in hearts failing due to myocardial infarction and aging. In addition, different phosphorylation mechanisms, which regulate the activities of Ca(2+)-cycling proteins in SL and SR membranes as well as Ca(2+)-binding proteins in myofibrils, become defective in the failing heart. Accordingly, it is suggested that subcellular remodeling involving defects in Ca(2+)-handling and Ca(2+)-binding proteins as well as their regulatory mechanisms is intimately associated with cardiac remodeling and heart failure due to myocardial infarction and aging.
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Avenue, Winnipeg, MB, Canada. nsdhalla@sbrc.ca
authors.forename: Naranjan S
authors.initials: NS
authors.lastname: Dhalla
authors.forename: Shashanka
authors.initials: S
authors.lastname: Rangi
authors.forename: Andrea P
authors.initials: AP
authors.lastname: Babick
authors.forename: Shelley
authors.initials: S
authors.lastname: Zieroth
authors.forename: Vijayan
authors.initials: V
authors.lastname: Elimban
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D002118:Calcium