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INNOSC Theranostics and
Pharmacological Sciences Cardiac metabolism in health and disease

chambers. 65,66 This response serves to decrease wall 8. Cardiac calcium homeostasis and
stress and oxygen consumption. 67-69 However, while signaling in health and diseases
it provides compensation, cardiac hypertrophy also
significantly increases the risk of heart failure and Calcium signaling plays a crucial role in cardiac cellular
malignant arrhythmias. 70,71 Previous studies have divided function, particularly within mitochondria, influencing
hypertrophic transformation of the heart into three stages: energy metabolism, redox balance, and cell fate
(i) hypertrophy with excessive load surpassing output, determination. Disruptions in mitochondrial calcium
(ii) compensatory hypertrophy maintaining workload handling significantly impact the progression of cardiac
and cardiac output, and (iii) heart failure with ventricular disease. In conditions such as ischemic heart disease,
dilation and a progressive decline in cardiac output. 66 disturbed calcium homeostasis leads to mitochondrial
dysfunction, reducing ATP production and triggering cell
A previous study has demonstrated that in cardiac death pathways, thereby exacerbating tissue damage during
hypertrophy, there is a suppression of the mitochondrial ischemia–reperfusion injury. 83,84 Similarly, in heart failure,
FAO gene PGC-1α, resulting in a metabolic shift aberrant calcium handling contributes to pathological
from mitochondrial FAO to glucose oxidation. remodeling, affecting excitation-contraction coupling and
72
This compensatory shift decreases oxygen demand prompting metabolic shifts. This dysfunctional signaling
compared to mitochondrial FAO, enhancing cardiac alters reliance on oxidative phosphorylation, favoring
20
efficiency. However, in hypertrophic conditions, cardiac glycolysis, and affects mitochondrial dynamics, exacerbating
mitochondrial function is impaired, prompting a reduction cardiac dysfunction. While initially adaptive, mitochondrial
in cardiac mitochondrial workload through a shift to changes can fuel chronic dysfunction, perpetuating cardiac
anaerobic glycolysis. 19,73 pathology. 80
In heart failure, altered energy metabolism and reduced A comprehensive understanding of the relationship
ATP production are well-documented, with levels dropping between mitochondrial calcium dynamics and cardiac
by approximately 30% compared to a normal adult disease necessitates a detailed exploration of the molecular
myocardium. 74,75 Concurrently, cardiac mitochondrial mechanisms governing calcium transport, buffering,
function decreases, further contributing to a total ATP and signaling within mitochondria. Identifying calcium-
production drop to 30%–40% of normal physiological dependent effectors such as the mitochondrial calcium
levels. 76,77 A majority of studies reveal reduced cardiac FAO uniporter complex, mitochondrial permeability transition
during heart failure, prompting the myocardium to shift pore, and calcium-sensitive enzymes holds promise for
its energy metabolism from substrates that demand high developing therapeutic interventions aimed at restoring
oxygen consumption (FAO) to primary energy sources mitochondrial calcium balance and preserving bioenergetics
with lower oxygen demands (glucose and ketone bodies) in cardiac diseases. 84
to maintain cardiac function, 20,78,79 aligning with concepts
described earlier. Mitochondrial calcium homeostasis serves not only
as a secondary messenger but also as a feedback and
While glycolysis increases in models of cardiac hypertrophy feed-forward mechanism in the development of cardiac
induced by abdominal aortic constriction, glucose oxidation myopathy, particularly associated with ETC dysfunction.
85
remains unchanged. 79,80 Impaired glucose oxidation in heart Moreover, calcium plays an intricate role in cardiomyocyte
failure is associated with mitochondrial dysfunction, reduced function, particularly in excitation–contraction coupling,
expression of glycolysis and glucose oxidation-related influencing various electrophysiological processes that
genes, and decreased abundance of pyruvate dehydrogenase impact cardiac metabolism and arrhythmias. While
complex, potentially contributing to cardiac dysfunction. 78,81 computational modeling has advanced our understanding,
Intriguingly, elevated glycolysis coexists with diminished critical questions regarding macromolecular regulation,
mitochondrial function and energetics in heart failure, calcium-dependent pathways, and the interplay between
20
culminating in ATP depletion and apoptosis, consequently electrophysiology and cardiac metabolism remain
reducing cardiac efficiency and function. 20 unanswered. Addressing these uncertainties through
85
Controversial data suggest that high-plasma FA in vitro and in silico studies could pave the way for improved
levels elevate cardiac mitochondrial FAO, potentially therapeutic strategies.
improving cardiac function under MI and heart failure 9. Discussion
conditions. 82,83 However, conflicting findings propose that
decreased mitochondrial FAO levels could be detrimental, The investigation into cardiac metabolism unveils a
further reducing total ATP production, which is already multifaceted landscape, delineating intricate patterns of
diminished in heart failure. energy utilization in both physiological and pathological

Volume 7 Issue 2 (2024) 5 doi: 10.36922/itps.2302