Impaired mitochondrial biogenesis is a common feature to myocardial hypertrophy and end-stage ischemic heart failure

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• 作者：Annalinda Pisano^a ; Bruna Cerbelli^a ; Elena Perli^a ; Maria Pelullo^b ; Valentina Bargelli^c ; Carmela Preziuso^a ; Massimiliano Mancini^a ; ^b ; Langping He^d ; Matthew GD Bates^d ; Joaquin R Lucena^e ; Paola Lilla Della Monica^f ; Giuseppe Familiari^g ; Vincenzo Petrozza^h ; Chiara Nediani^c ; Robert W Taylor^d ; Giulia d&rsquo ; Amati^a ; Carla Giordano^a ; ^{carla.giordano@uniroma1.it" class="auth_mail" title="E-mail the corresponding author}
• 关键词：HF ; heart failure ; LV ; left ventricular ; OXPHOS ; oxidative phosphorylation ; mtDNA ; mitochondrial DNA ; MIC ; mitochondrial cardiomyopathies ; LCM ; laser capture microdissection ; COX ; cytochrome c oxidase ; SDH ; succinate dehydrogenase ; TEM ; transmission electron microscopy ; PPARα ; peroxisome proliferator-activated receptor alpha PPARA ; PGC-1α ; peroxisome proliferator-activated receptor gamma coactivator 1 alpha ; PPARGC1A ; NPPA ; natriuretic peptide A ; NRF1 ; nuclear respiratory factor 1 ; ERRα ; estroge
• 刊名：Cardiovascular Pathology
• 出版年：2016
• 出版时间：March-April 2016
• 年：2016
• 卷：25
• 期：2
• 页码：103-112
• 全文大小：1437 K

文摘

Mitochondrial (mt) DNA depletion and oxidative mtDNA damage have been implicated in the process of pathological cardiac remodeling. Whether these features are present in the early phase of maladaptive cardiac remodeling, that is, during compensated cardiac hypertrophy, is still unknown.

We compared the morphologic and molecular features of mt biogenesis and markers of oxidative stress in human heart from adult subjects with compensated hypertrophic cardiomyopathy and heart failure. We have shown that mtDNA depletion is a constant feature of both conditions. A quantitative loss of mtDNA content was associated with significant down-regulation of selected modulators of mt biogenesis and decreased expression of proteins involved in mtDNA maintenance. Interestingly, mtDNA depletion characterized also the end-stage phase of cardiomyopathies due to a primary mtDNA defect. Oxidative stress damage was detected only in failing myocardium.