Cardiac dysfunction, mitochondrial architecture, energy production, and inflammatory pathways: interrelated aspects in endotoxemia and sepsis

ALVAREZ, SILVIA; VICO, TAMARA; VANASCO, VIRGINIA

INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND CELLULAR BIOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2016 vol. 81 p. 307 - 314

1357-2725

Septic patients with myocardial dysfunction have a 3-fold increase in mortality comparedwith patients without cardiovascular impairment, and usually show myocarditis, disruptionof the contractile apparatus, increased amounts of interstitial collagen, and damagedmitochondria. The presence of nitric oxide and cytokines in cardiac tissue constitute themolecular markers and the intracellular messengers of inflammatory conditions in the heartdue to the onset of sepsis and endotoxemia, derived from the nuclear factor-B pathwayactivation and proinflammatory gene transcription. Sepsis occurs with an exacerbatedinflammatory response that damages tissue mitochondria and impaired bioenergeticprocesses. The heart consumes 20-30 times its own weight in adenosine triphosphateevery day, and 90% of this molecule is derived from mitochondrial oxidativephosphorylation. Cardiac energy management is comprised in sepsis and endotoxemia;both a deficit in energy production and alterations in the source of energy substrates arebelieved to be involved in impaired cardiac function. Although several hypotheses try toexplain the molecular mechanisms underlying the complex condition of sepsis andendotoxemia, the current view is that these syndromes are the result of an intricatebalance between prevailing levels of mitochondrial stress, biogenesis/autophagy signalingand mitochondria quality control processes, rather on a single factor. The aim of thisreview is to discuss current hypothesis of cardiac dysfunction related to energymetabolism and mitochondrial function in experimental models of sepsis and endotoxemia,and to introduce the importance of lipids (mainly cardiolipin) in the mechanism of cardiacenergy mismanagement in these inflammatory conditions.