Exploiting the Pleiotropic Antioxidant Effects of Established Drugs in Cardiovascular Disease

Abstract

Cardiovascular disease is a leading cause of death and reduced quality of life worldwide. Arterial vessels are a primary target for endothelial dysfunction and atherosclerosis, which is accompanied or even driven by increased oxidative stress. Recent research in this field identified different sources of reactive oxygen and nitrogen species contributing to the pathogenesis of endothelial dysfunction. According to lessons from the past, improvement of endothelial function and prevention of cardiovascular disease by systemic, unspecific, oral antioxidant therapy are obviously too simplistic an approach. Source- and cell organelle-specific antioxidants as well as activators of intrinsic antioxidant defense systems might be more promising. Since basic research demonstrated the contribution of different inflammatory cells to vascular oxidative stress and clinical trials identified chronic inflammatory disorders as risk factors for cardiovascular events, atherosclerosis and cardiovascular disease are closely associated with inflammation. Therefore, modulation of the inflammatory response is a new and promising approach in the therapy of cardiovascular disease. Classical anti-inflammatory therapeutic compounds, but also established drugs with pleiotropic immunomodulatory abilities, demonstrated protective effects in various models of cardiovascular disease. However, results from ongoing clinical trials are needed to further evaluate the value of immunomodulation for the treatment of cardiovascular disease.

Targeting vascular (endothelial) dysfunction

“…The central role of the cardiovascular system is the transportation of nutrients, biomolecules and signalling molecules, and importantly, transport of gasses to and from all organs, tissues and cells (Pries and Kuebler, ; Mikhed et al , ). In addition, the cardiovascular system is an important regulator of host defence by the immune system (Libby et al , ; Pries and Kuebler, ; Karbach et al ., ) and blood haemostasis/coagulation (Arnout et al , ; Pries and Kuebler, ; Steven et al , ). The endothelium, a mono‐layer of cells lining the inner /luminal surface of blood vessels, acts as a barrier to control the exchange of nutrients, biomolecules and messengers with surrounding tissues.…”

“…Since the development of endothelial (vascular) dysfunction is a multi‐factorial process, we will concentrate on some of its most important components in the following sections (Figure ). Among the most important vasoactive compounds produced by endothelial cells are • NO, EDHF, prostacyclin and endothelin‐1 since they not only affect vascular tone but also the activity and adhesion of platelets and immune cells to the endothelium (Pries and Kuebler, ; Selivanova et al , ; Karbach et al , ; Steven et al , ). The redox regulation of their production was previously reviewed in detail (Kahler et al , ; ; Bachschmid et al , ; Daiber et al , ; Schulz et al , ) and is discussed extensively in this virtual collection (Daiber et al , ).…”

Functional and Biochemical Endothelial Profiling In Vivo in a Murine Model of Endothelial Dysfunction; Comparison of Effects of 1-Methylnicotinamide and Angiotensin-converting Enzyme Inhibitor

“…Vascular dysfunction is associated with activation of pro-inflammatory signaling molecules including adhesion molecules, chemokines and cytokines (Karbach et al, 2014; Steven et al, 2015). There is also evidence that ROS play an important role in vascular inflammation (Zhou et al, 2011) and tissue damage (Mittal et al, 2014).…”

Passiflora quadrangularis L. PREVENTS EXPERIMENTAL HYPERTENSION AND VASCULAR REMODELLING IN RATS EXPOSED TO NITRIC OXIDE DEFICIT

“…Therefore, NO cascade constitutes a key target for the management of hypertension and related cardiovascular disorders. Angiotensin converting enzyme inhibitors, statins and some beta blocking agents are among the drugs that favour NO production, reduce oxidative stress and ameliorate endothelial lesions (16,17).…”