Metabolic Remodeling and Implicated Calcium and Signal Transduction Pathways in the Pathogenesis of Heart Failure

Abstract

The heart is an organ with high-energy demands in which the mitochondria are most abundant. They are considered the powerhouse of the cell and occupy a central role in cellular metabolism. The intermyofibrillar mitochondria constitute the majority of the three-mitochondrial subpopulations in the heart. They are also considered to be the most important in terms of their ability to participate in calcium and cellular signaling, which are critical for the regulation of mitochondrial function and adenosine triphosphate (ATP) production. This is because they are located in very close proximity with the endoplasmic reticulum (ER), and for the presence of tethering complexes enabling interorganelle crosstalk via calcium signaling. Calcium is an important second messenger that regulates mitochondrial function. It promotes ATP production and cellular survival under physiological changes in cardiac energetic demand. This is accomplished in concert with signaling pathways that regulate both calcium cycling and mitochondrial function. Perturbations in mitochondrial homeostasis and metabolic remodeling occupy a central role in the pathogenesis of heart failure. In this review we will discuss perturbations in ER-mitochondrial crosstalk and touch on important signaling pathways and molecular mechanisms involved in the dysregulation of calcium homeostasis and mitochondrial function in heart failure.

U-shaped association between serum calcium and in-hospital mortality in diabetes patients with congestive heart failure: a cohort study

“…Furthermore, a complex interplay exists between cardiovascular well-being and mineral homeostasis. Calcium functions as a pivotal secondary messenger, exerting a critical role in governing mitochondrial activity and upholding excitation–contraction coupling mechanisms 37 . Perturbation of calcium homeostasis detrimentally impacts the contractile proficiency of the heart, culminating in compromised cardiac performance 38 .…”

Combining three independent pathological stressors induces a heart failure with preserved ejection fraction phenotype

“…Increases in Ca 2+ influx enhances contraction to meet increased physiological and pathological demands ( 21 , 54 – 56 ). The increased cellular Ca 2+ causes increased contraction but also elicits a host of responses including cardiac hypertrophy ( 21 , 54 – 56 ), metabolic reprogramming ( 57 ), and can lead to cell death ( 22 , 58 ). There is a robust literature linking increased Ca 2+ influx in disease to cardiac remodeling ( 21 , 54 – 56 , 59 ).…”

“…Cardiac hypertrophy is also associated with the diastolic dysfunction and elevated diastolic filling pressure observed in HFpEF ( 9 , 69 ). Pathophysiological cardiac hypertrophy in patients with HFpEF likely involves impaired Ca 2+ handling ( 9 ), myocardial fibrosis ( 4 , 9 ), oxidative stress ( 9 , 70 ), cell death ( 9 , 22 , 58 ), metabolic reprogramming ( 57 ), and induction of fetal genes ( 9 , 71 ). All of these features are induced in the 3-Hit mouse model characterized in the present work.…”

Estimation of Serum Calcium Level in the Patients of Hypertension

“…12,13 Calcium is one of the important ion of human body which maintain the cellular transportation, signal transduction etc. 14 Calcium contributed along with other ions like as sodium, potassium and chloride in the disturbance of blood pressure. 15 Essential hypertension can be caused by a change in cellular transportation of ions due to a change in calcium ion concentration.…”