title: Potential role and mechanisms of subcellular remodeling in cardiac dysfunction due to ischemic heart disease.
abstract: Several studies have revealed varying degrees of changes in sarcoplasmic reticular and myofibrillar activities, protein content, gene expression and intracellular Ca-handling during cardiac dysfunction due to ischemia-reperfusion (I/R); however, relatively little is known about the sarcolemmal and mitochondrial alterations, as well as their mechanisms in the I/R hearts. Because I/R is associated with oxidative stress and intracellular Ca-overload, it has been indicated that changes in subcellular activities, protein content and gene expression due to I/R are related to both oxidative stress and Ca-overload. Intracellular Ca-overload appears to induce changes in subcellular activities, protein contents and gene expression (subcellular remodeling) by activation of proteases and phospholipases, as well as by affecting the genetic apparatus, whereas oxidative stress is considered to cause oxidation of functional groups of different subcellular proteins in addition to modifying the genetic machinery. Ischemic preconditioning, which is known to depress the development of both intracellular Ca-overload and oxidative stress due to I/R, was observed to attenuate the I/R-induced subcellular remodeling and improve cardiac performance. It is suggested that a combination therapy with antioxidants and interventions, which reduce the development of intracellular Ca-overload, may improve cardiac function by preventing or attenuating the occurrence of subcellular remodeling due to ischemic heart disease. It is proposed that defects in the activities of subcellular organelles may serve as underlying mechanisms for I/R-induced cardiac dysfunction under acute conditions, whereas subcellular remodeling due to alterations in gene expression may explain the impaired cardiac performance under chronic conditions of I/R.
authors.affiliation: Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, and Faculty of Medicine, University of Manitoba, Winnipeg, Canada. nsdhalla@sbrc.ca
authors.forename: Naranjan S
authors.initials: NS
authors.lastname: Dhalla
authors.forename: Harjot K
authors.initials: HK
authors.lastname: Saini
authors.forename: Paramjit S
authors.initials: PS
authors.lastname: Tappia
authors.forename: Rajat
authors.initials: R
authors.lastname: Sethi
authors.forename: Sushma A
authors.initials: SA
authors.lastname: Mengi
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Gupta
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism*; D002317:Cardiovascular Agents / Q000627:therapeutic use; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008929:Mitochondria, Heart / Q000378:metabolism; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D012508:Sarcolemma / Q000378:metabolism; D016276:Ventricular Function; D020257:Ventricular Remodeling
chemical_list: D000975:Antioxidants; D002317:Cardiovascular Agents; D002118:Calcium