What is chronic heart failure (CHF)?

Chronic heart failure (CHF), also known simply as heart failure, is a medical condition in which the heart is unable to pump blood efficiently enough to meet the body’s needs. It is a progressive condition that develops over time and can have a significant impact on a person’s quality of life and overall health. Chronic heart failure is a common cardiovascular disorder and a leading cause of hospitalization and mortality worldwide.


What is the relationship between CHF and oxidative stress?

Oxidative stress plays a significant role in the pathophysiology of heart failure. Here’s how chronic heart failure and oxidative stress are related:


  • Myocardial Damage: Chronic heart failure often results from various underlying cardiovascular conditions, such as coronary artery disease, myocardial infarction (heart attack), and cardiomyopathy, which can lead to myocardial damage and dysfunction. Ischemic injury to the heart tissue, characterized by reduced blood flow and oxygen supply, triggers the production of reactive oxygen species (ROS) and oxidative stress. ROS can further exacerbate myocardial damage by inducing oxidative modifications to cellular components, such as lipids, proteins, and DNA, leading to cellular dysfunction and apoptosis (cell death).


  • Inflammation: Chronic heart failure is associated with low-grade systemic inflammation, characterized by increased levels of pro-inflammatory cytokines and immune cell activation. Inflammatory processes contribute to oxidative stress by promoting the activation of NADPH oxidases (enzymes that produce ROS), enhancing mitochondrial ROS production, and depleting antioxidant defenses. Chronic oxidative stress and inflammation create a vicious cycle, further exacerbating myocardial injury and dysfunction.


  • Endothelial Dysfunction: Endothelial dysfunction, characterized by impaired nitric oxide (NO) bioavailability and endothelial nitric oxide synthase (eNOS) activity, is a hallmark feature of chronic heart failure. Reduced NO levels and eNOS uncoupling lead to impaired vasodilation, increased vascular tone, and endothelial dysfunction. Oxidative stress plays a critical role in endothelial dysfunction by scavenging NO, promoting eNOS uncoupling, and generating vasoconstrictive ROS species. Endothelial dysfunction contributes to impaired coronary blood flow regulation, increased vascular resistance, and adverse cardiac remodeling in heart failure.


  • Cardiac Remodeling: Chronic heart failure is characterized by maladaptive cardiac remodeling, including left ventricular hypertrophy, dilation, fibrosis, and chamber dysfunction. Oxidative stress contributes to adverse cardiac remodeling by promoting cardiomyocyte hypertrophy, interstitial fibrosis, and extracellular matrix remodeling. ROS activate profibrotic signaling pathways, such as transforming growth factor-β (TGF-β) and mitogen-activated protein kinase (MAPK), leading to collagen deposition and myocardial stiffening. Oxidative stress-induced cardiac remodeling further impairs cardiac function and exacerbates heart failure progression.


  • Mitochondrial Dysfunction: Mitochondrial dysfunction is a key feature of chronic heart failure and contributes to impaired myocardial energetics, contractile dysfunction, and apoptosis. Oxidative stress disrupts mitochondrial function by impairing electron transport chain activity, reducing ATP production, and promoting mitochondrial ROS generation. ROS-induced mitochondrial damage leads to further oxidative stress and bioenergetic impairment, creating a vicious cycle of mitochondrial dysfunction and oxidative stress in heart failure.


Overall, oxidative stress plays a critical role in the pathogenesis of chronic heart failure by contributing to myocardial damage, inflammation, endothelial dysfunction, adverse cardiac remodeling, and mitochondrial dysfunction.