Treating oxidative stress in heart failure: past, present and future

Abstract

Advances in cardiovascular research have identified oxidative stress as an important pathophysiological pathway in the development and progression of heart failure. Oxidative stress is defined as the imbalance between the production of reactive oxygen species (ROS) and the endogenous antioxidant defence system. Under physiological conditions, small quantities of ROS are produced intracellularly, which function in cell signalling, and can be readily reduced by the antioxidant defence system. However, under pathophysiological conditions, the production of ROS exceeds the buffering capacity of the antioxidant defence system, resulting in cell damage and death. Over the last decades several studies have tried to target oxidative stress with the aim to improve outcome in patients with heart failure, with very limited success. The reasons as to why these studies failed to demonstrate any beneficial effects remain unclear. However, one plausible explanation might be that currently employed strategies, which target oxidative stress by exogenous inhibition of ROS production or supplementation of exogenous antioxidants, are not effective enough, while bolstering the endogenous antioxidant capacity might be a far more potent avenue for therapeutic intervention. In this review, we provide an overview of oxidative stress in the pathophysiology of heart failure and the strategies utilized to date to target this pathway. We provide novel insights into modulation of endogenous antioxidants, which may lead to novel therapeutic strategies to improve outcome in patients with heart failure.

Salivary Oxidative Stress Increases with the Progression of Chronic Heart Failure

“…HF is a clinical disease entity of multifactorial etiology connected with hypercholesterolemia, hypertension, diabetes, smoking, unbalanced diet, and sedentary lifestyle [1,2,4]. Oxidative stress is considered both the primary and secondary cause of HF, similarly to many other systemic diseases [5][6][7]. Indeed, the key contribution of oxidative stress in HF has been demonstrated in the pathogenesis of genetic, neurodegenerative, neoplastic, and metabolic diseases.…”

“…Studies on HF indicate that an important role in its pathogenesis is played by oxidative stress [5][6][7]. This process creates an imbalance between the production of reactive oxygen species (ROS) and antioxidative defense, which leads to oxidative damage to proteins, lipids, and nucleic acids, causing structural damage to cells as well as disturbances in tissue integrity [8].…”

“…This process creates an imbalance between the production of reactive oxygen species (ROS) and antioxidative defense, which leads to oxidative damage to proteins, lipids, and nucleic acids, causing structural damage to cells as well as disturbances in tissue integrity [8]. Indeed, the role of oxidative stress has been confirmed in the course of: Endothelial dysfunction, interstitial fibrosis of the heart, cardiomyocyte hypertrophy, and heart extracellular matrix remodeling [5,7,9,10]. Moreover, it has been demonstrated that in the early stages of HF, increased activity of antioxidant enzymes is the basic compensatory mechanism aimed at maintaining adequate blood flow and perfusion of tissues.…”

“…Moreover, it has been demonstrated that in the early stages of HF, increased activity of antioxidant enzymes is the basic compensatory mechanism aimed at maintaining adequate blood flow and perfusion of tissues. However, HF progression leads to the depletion of antioxidant reserves and, along with increased free radical production, contributes to further progression of the disease [5,7,9,10].…”

“…However, salivary redox homeostasis has not been evaluated yet in patients with chronic heart failure. Considering that oxidative stress plays a key role in HF pathogenesis [5][6][7], secretory dysfunction of salivary glands may also occur in HF patients, similarly to other diseases with proven etiology of oxidative stress. Indeed, a relationship between oxidative stress and impaired salivary gland function has been demonstrated in obesity [23,24], insulin resistance [25,26], type 1 diabetes [27], and psoriasis [28].…”