Energy metabolism in heart failure and remodelling

Abstract

Myocytes of the failing heart undergo impressive metabolic remodelling. The time line for changes in the pathways for ATP synthesis in compensated hypertrophy is: flux through the creatine kinase (CK) reaction falls as both creatine concentration ([Cr]) and CK activity fall; increases in [ADP] and [AMP] lead to increases in glucose uptake and utilization; fatty acid oxidation either remains the same or decreases. In uncompensated hypertrophy and in other forms of heart failure, CK flux and fatty acid oxidation are both lower; any increases in glucose uptake and utilization are not sufficient to compensate for overall decreases in the capacity for ATP supply and [ATP] falls. Metabolic remodelling is under transcriptional and post-transcriptional control. The lower metabolic reserve of the failing heart contributes to impaired contractile reserve.

Muscle Creatine Kinase Deficiency Triggers Both Actin Depolymerization and Desmin Disorganization by Advanced Glycation End Products in Dilated Cardiomyopathy

“…Accordingly the ADP/ATP ratio was raised in the SRF HKO heart (SRF HKO 2.74 Ϯ 0.62 versus controls, 0.82 Ϯ 0.28; pval ϭ 0.014). Altogether, these results show that energy reserve is altered in the failing SRF-deficient heart as in most models of heart failure (20). Up-regulation of AK1 and ATP-synthase subunit d likely reflects an attempt of compensatory response to maintain ATP synthesis (supplemental Tables S1 and S2).…”

“…Importance of MCK Regulation by SRF for Thin Filament Stability-The failing heart is characterized by a metabolic remodeling that includes a fall in CK activity and a decrease of fatty acid oxidation, whereas the potential increase in glucose uptake and utilization driven by the [ADP] and [AMP] increase is not sufficient to compensate for overall decreases in the capacity for ATP supply (3,20). The reduction of the contractile reserve is also due to alterations in the pool of contractile proteins, through down-regulation of expression, shift of isoforms, FIGURE 8.…”

E2F1-dependent miR-421 regulates mitochondrial fragmentation and myocardial infarction by targeting Pink1

“…Heart failure is the common end stage of cardiovascular diseases and represents a decline in cardiac function. Heart failure involves the impairment of cardiomyocytes in energy metabolism, calcium homeostasis, reactive oxygen species production and cell death [2][3][4] . Since mitochondria are the major ATP and reactive oxygen species production organelle in cardiomyocytes, mitochondrial malfunction is tightly related to cardiovascular diseases and contributes to heart failure.…”

Prospects for Cytoprotectors Use in the Elderly Patients Through the Example of Calcified Aortic Stenosis and Ischemic Heart Disease

“…Биоэнерегетические особенности мышцы сердца -возможности применения цитопротекторов В настоящее время среди ведущих кардиологов об-суждается гипотеза «энергетического голода», рас-Цитопротекторы при кальцинированном аортальном стенозе и ИБС сматривающая недостаточное образование АТФ, в том числе и вследствие повышения уровня окисления жирных кислот, в качестве пускового механизма дис-функции миокарда [21]. Известно, что сердечная мыш-ца является основным потребителем энергии в орга-низме человека.…”