Mitochondrial centrality in heart failure

Abstract

A number of observations have shown that mitochondria are at the center of the pathophysiology of the failing heart and mitochondrial-based oxidative stress (OS), myocardial apoptosis, and cardiac bioenergetic dysfunction are implicated in the progression of heart failure (HF), as shown by both clinical studies and animal models. In this manuscript, we review the body of evidence that multiple defects in mitochondria are central and primary to HF progression. In addition, novel approaches to therapeutic targeting of mitochondrial bioenergetic, biogenic, and signaling abnormalities that can impact HF are discussed.

Perilipin 5, a lipid droplet-associated protein, provides physical and metabolic linkage to mitochondria

“…Emerging evidence suggests LDs and mitochondria are intimately and functionally related. Cells from oxidative tissues have high and fl uctuating energy demands and exposure to FA that require effi cient coupling between energy storage in LDs and utilization in mitochondria ( 7,8 ). Mitochondrial dysfunction results in prominent lipid accumulation and tissue-specifi c metabolic disturbances in both mice and humans ( 6 ).…”

“…␤ -oxidation using metabolic radioactive labeling was performed in control or Plin5-YFP cells as described ( 30 ). Cells were seeded in a 24-multiwell dish and exposed to DMEM supplemented with 0.24 mmol/l fatty acidfree albumin (BSA), 0.5 mmol/l L-carnitine, 20 mmol/l HEPES, and [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C] palmitate (1.0 Ci/ml, 0.017 mmol/l) with 5 mmol/l glucose ( 30 ). After CO 2 trapping, the incubation media were transferred to new tubes and assayed for labeled ␤ -oxidation regulator, along with humidifi cation and an objective heater.…”

Modulation of Reactive Oxygen Species and Collagen Synthesis by Angiotensin II in Cardiac Fibroblasts

“…Mitochondrial oxidative stress and damage seems also to play a major role in the development and progression of left ventricular remodeling and failure after myocardial infarction [136,137]. In the failing ventricular myocard from patients with end-stage heart failure a marked decline in mitochondrial Mn-SOD protein and activity is detected [138].…”

Volatile and Intravenous Anesthesia Alter Rat Liver Proteins: Proteomic Time Course Analysis of Rat Liver Proteins

“…During oxidative stress, the intracellular redox balance is disrupted with increased production and accumulation of ROS, which may lead to mitochondrial dysfunction and subsequent ATP production [32]. Such species are scavenged by the catalytic activities of Cu-Zn SOD and CAT and non-enzymatically by GST [11].…”