Modulation of sarcoplasmic reticulum Ca(2+) cycling in systolic and diastolic heart failure associated with aging.
Hypertension, atherosclerosis, and resultant chronic heart failure (HF) reach epidemic proportions among older persons, and the clinical manifestations and the prognoses of these worsen with increasing age. Thus, age per se is the major risk factor for cardiovascular disease. Changes in cardiac cell phenotype that occur with normal aging, as well as in HF associated with aging, include deficits in ss-adrenergic receptor (ss-AR) signaling, increased generation of reactive oxygen species (ROS), and altered excitation-contraction (EC) coupling that involves prolongation of the action potential (AP), intracellular Ca(2+) (Ca(i)(2+)) transient and contraction, and blunted force- and relaxation-frequency responses. Evidence suggests that altered sarcoplasmic reticulum (SR) Ca(2+) uptake, storage, and release play central role in these changes, which also involve sarcolemmal L-type Ca(2+) channel (LCC), Na(+)-Ca(2+) exchanger (NCX), and K(+) channels. We review the age-associated changes in the expression and function of Ca(2+) transporting proteins, and functional consequences of these changes at the cardiac myocyte and organ levels. We also review sexual dimorphism and self-renewal of the heart in the context of cardiac aging and HF.
Janczewski
Andrzej M
AM
janczewskia@upmc.edu
Lakatta
Edward G
EG
D000222:Adaptation, Physiological; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D018450:Disease Progression; D005260:Female; D054144:Heart Failure, Diastolic / Q000201:enzymology / Q000453:epidemiology / Q000503:physiopathology*; D054143:Heart Failure, Systolic / Q000201:enzymology / Q000453:epidemiology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D032342:Muscle Cells / Q000473:pathology; D011379:Prognosis; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis; D012307:Risk Factors; D012519:Sarcoplasmic Reticulum / Q000201:enzymology* / Q000473:pathology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D012737:Sex Factors; D015398:Signal Transduction; D013312:Stress, Physiological; D014481:United States / Q000453:epidemiology
D011943:Receptors, Adrenergic, beta; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases