Redox-sensitive mechanisms underlying vascular dysfunction in heart failure

Abstract

Regardless of the progress in therapeutic drugs and devices to treat heart failure (HF) during the last few years, the clinical outcome of this disease remains deleterious. Impaired left ventricular function leads to neurohumoral activation, altered local shear forces, and hypoxia, which might give rise to inflammatory processes within the vasculature. Among those, the imbalance of the redox equilibrium toward increased concentrations of reactive oxygen species (ROS) is particularly important, as it affects the integrity of vascular function. Apart from injured or dysfunctional cardiomyocytes, vascular dysfunction has been demonstrated to play a crucial role in the development and progression of HF, which makes it an interesting target for new HF therapies. The mechanisms that initiate vascular dysfunction in HF pathogenesis and the processes leading to oxidative stress are not yet fully elucidated. However, oxidative stress promotes a variety of redox-sensitive mechanisms contributing to vascular dysfunction in HF. Here, we will summarize the sources of ROS in the vasculature, elucidate the impact of oxidative stress on functional and structural vascular remodeling, and consider the link to vascular dysfunction. Furthermore, we will point out the importance of vascular dysfunction in HF and discuss therapeutic options.

Keywords::

• vascular
• dysfunction
• reactive oxygen species
• heart failure

Declaration of interest

This work was supported by the Deutsche Forschungsgemeinschaft [KL 2516/1–1 to A.K.; BA 1870/7–1, BA 1870/9–1 and BA 1870/10–1 to S.B]. There are no further disclosures.