Mitochondria, Myocardial Remodeling, and Cardiovascular Disease

Abstract

The process of muscle remodeling lies at the core of most cardiovascular diseases. Cardiac adaptation to pressure or volume overload is associated with a complex molecular change in cardiomyocytes which leads to anatomic remodeling of the heart muscle. Although adaptive at its beginnings, the sustained cardiac hypertrophic remodeling almost unavoidably ends in progressive muscle dysfunction, heart failure and ultimately death. One of the features of cardiac remodeling is a progressive impairment in mitochondrial function. The heart has the highest oxygen uptake in the human body and accordingly it has a large number of mitochondria, which form a complex network under constant remodeling in order to sustain the high metabolic rate of cardiac cells and serve as Ca(2+) buffers acting together with the endoplasmic reticulum (ER). However, this high dependence on mitochondrial metabolism has its costs: when oxygen supply is threatened, high leak of electrons from the electron transport chain leads to oxidative stress and mitochondrial failure. These three aspects of mitochondrial function (Reactive oxygen species signaling, Ca(2+) handling and mitochondrial dynamics) are critical for normal muscle homeostasis. In this article, we will review the latest evidence linking mitochondrial morphology and function with the process of myocardial remodeling and cardiovascular disease.

Leptin-induced mitochondrial fusion mediates hepatic lipid accumulation

“…In contrast, proteins like dynamin-related protein-1 (Drp1) and fission protein-1 (Fis1) controlling mitochondrial fission. 18 In type 2 diabetic patients, smaller mitochondria has been found, and mitochondrial fusion protein levels were decreased. 19,20 In skeletal muscle, mitochondrial fusion protein modulates insulin signal pathway and glucose homeostasis via regulating mitochondrial function also have been reported.…”

Selenium and coenzyme Q10 interrelationship in cardiovascular diseases – A clinician's point of view

“…In cardiac disease, as seen in heart failure, the cytosolic and mitochondrial ROS become distorted, leading to oxidative imbalance, mitochondrial dysfunction and eventually to cell death [4]. It has been demonstrated that the more the cardiac function in this patient group is impaired, the more signs of apoptosis and oxidative stress appear [5][6][7].…”

Loss of mitochondrial exo/endonuclease EXOG affects mitochondrial respiration and induces ROS-mediated cardiomyocyte hypertrophy

“…Low levels of ROS may be protective (7,23) and affect signaling pathways that may stimulate growth (5). However, an imbalance between ROS production and the normal cellular antioxidant defense system will lead to oxidative stress and potentially in DNA damage (10).…”