The role of mitochondrial dysfunction in cardiovascular disease: a brief review

Abstract

Cardiovascular disease (CVD) is a leading cause of mortality worldwide. Proper mitochondrial function is necessary in tissues and organs that are of high energy demand, including the heart. Mitochondria are very sensitive to nutrient and oxygen supply and undergo metabolic adaptation to the changing environment. In CVD, such an adaptation is impaired, which, in turn, leads to a progressive decline of the mitochondrial function associated with abnormalities in the respiratory chain and ATP synthesis, increased oxidative stress, and loss of the structural integrity of mitochondria. Uncoupling of the electron transport chain in dysfunctional mitochondria results in enhanced production of reactive oxygen species, depletion of cell ATP pool, extensive cell damage, and apoptosis of cardiomyocytes. Mitophagy is a process, during which cells clear themselves from dysfunctional and damaged mitochondria using autophagic mechanism. Deregulation of this process in the failing heart, accumulation of dysfunctional mitochondria makes the situation even more adverse. In cardiac pathology, aberrations of the activity of the respiratory chain and ATP production may be considered as a core of mitochondrial dysfunction. Indeed, therapeutic restoration of these key functional properties can be considered as a primary goal for improvement of mitochondrial dysfunction in CVD. Key messages Mitochondrial dysfunction plays a crucial role in cardiovascular disease pathogenesis. Cardiovascular disease is associated with altered mithochondrial biogenesis and clearance. In cardiovascular disease, impaired mitochondrial function results in decreased ATP production and enhanced ROS formation.

Possible Role of Mitochondrial DNA Mutations in Chronification of Inflammation: Focus on Atherosclerosis

“…The link between mitochondrial dysfunction and atherosclerosis has been the subject of extensive research [85]. Besides cardiovascular disease, several chronic human pathologies are known to be associated with mitochondrial dysfunction.…”

Mitochondrial MiRNA in Cardiovascular Function and Disease

“…ROS derived from mitochondria could stabilize hypoxia-inducible factor 1α (HIF-1α), and HIF-1α, in turn, promotes VEGF expression, contributing to angiogenesis [9]. Mitochondrial dysfunction is associated with the development of many diseases, including cardiovascular diseases [8,[10][11][12].…”

Macrophage autophagy regulates mitochondria‐mediated apoptosis and inhibits necrotic core formation in vulnerable plaques

“…Increased opening of mitochondrial permeability transition pore (MPTP) results in mitochondrial dysfunction, which includes mitochondrial membrane potential (MMP) loss, cytochrome c loss from the intermembrane space, excessive reactive oxygen species (ROS) generation and mitochondrial fission . Recent data suggest that mitochondrial dysfunction plays a crucial role in macrophage death in advanced lesion . Also, cholesterol loading of mouse peritoneal macrophages induces cells apoptosis by damaging mitochondria .…”

“…22 Recent data suggest that mitochondrial dysfunction plays a crucial role in macrophage death in advanced lesion. 23,24 Also, cholesterol loading of mouse peritoneal macrophages induces cells apoptosis by damaging mitochondria. 25 Autophagy is the main way to degrade impaired mitochondria.…”