Loss of cardiac tetralinoleoyl cardiolipin in human and experimental heart failure.
The mitochondrial phospholipid cardiolipin is required for optimal mitochondrial respiration. In this study, cardiolipin molecular species and cytochrome oxidase (COx) activity were studied in interfibrillar (IF) and subsarcolemmal (SSL) cardiac mitochondria from Spontaneously Hypertensive Heart Failure (SHHF) and Sprague-Dawley (SD) rats throughout their natural life span. Fisher Brown Norway (FBN) and young aortic-constricted SHHF rats were also studied to investigate cardiolipin alterations in aging versus pathology. Additionally, cardiolipin was analyzed in human hearts explanted from patients with dilated cardiomyopathy. A loss of tetralinoleoyl cardiolipin (L(4)CL), the predominant species in the healthy mammalian heart, occurred during the natural or accelerated development of heart failure in SHHF rats and humans. L(4)CL decreases correlated with reduced COx activity (no decrease in protein levels) in SHHF cardiac mitochondria, but with no change in citrate synthase (a matrix enzyme) activity. The fraction of cardiac cardiolipin containing L(4)CL became much lower with age in SHHF than in SD or FBN mitochondria. In summary, a progressive loss of cardiac L(4)CL, possibly attributable to decreased remodeling, occurs in response to chronic cardiac overload, but not aging alone, in both IF and SSL mitochondria. This may contribute to mitochondrial respiratory dysfunction during the pathogenesis of heart failure.
Sparagna
Genevieve C
GC
Department of Integrative Physiology, University of Colorado Cardiovascular Institute, University of Colorado at Boulder, Boulder, CO 80309-0354, USA. sparagna@colorado.edu
Chicco
Adam J
AJ
Murphy
Robert C
RC
Bristow
Michael R
MR
Johnson
Christopher A
CA
Rees
Meredith L
ML
Maxey
Melissa L
ML
McCune
Sylvia A
SA
Moore
Russell L
RL
D000328:Adult; D000368:Aged; D000375:Aging; D000818:Animals; D002308:Cardiolipins / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011914:Rats, Inbred BN; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley
D002308:Cardiolipins; C523441:tetralinoleoylcardiolipin; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase