Therapeutic Approach in the Improvement of Endothelial Dysfunction: The Current State of the Art

Abstract

The endothelium has a central role in the regulation of blood flow through continuous modulation of vascular tone. This is primarily accomplished by balanced release of endothelial relaxing and contractile factors. The healthy endothelial cells are essential for maintenance of vascular homeostasis involving antioxidant, anti-inflammatory, pro-fibrinolytic, anti-adhesive, or anticoagulant effects. Oppositely, endothelial dysfunction is primarily characterized by impaired regulation of vascular tone as a result of reduced endothelial nitric oxide (NO) synthase activity, lack of cofactors for NO synthesis, attenuated NO release, or increased NO degradation. So far, the pharmacological approach in improving/reversal of endothelial dysfunction was shown to be beneficial in clinical trials that have investigated actions of different cardiovascular drugs. The aim of this paper was to summarize some of the latest clinical findings related to therapeutic possibilities for improving endothelial dysfunction in different pathological conditions. In the majority of presented clinical investigations, the assessment of improvement or reversal of endothelial dysfunction was performed through the flow-mediated dilatation measurement, and in some of those endothelial progenitor cells' count was used for the same purpose. Still, given the fast and continuous development of this field, the evidence acquisition included the MEDLINE data base screening and the selection of articles published between 2010 and 2012.

Angiotensin receptor blockers & endothelial dysfunction

“…The response of different blood vessels to various relaxing and contractile vasoactive substances can be partly or entirely endothelium-dependent, as well as completely endothelium-independent4567. Although endothelium has the ability of producing different vasodilator substances, nearly all stimuli that ultimately produce endothelium-dependent vasodilatation include endothelial NO.…”

“…On the other hand, a chronic exposure to cardiovascular risk factors such as hyperglycaemia, hyperlipidaemia, hypertension, hyperhomocysteinemia, smoking, sedentary lifestyle, obesity, infections by Chlamydia pneumoniae , Helicobacter pylori , Cytomegalovirus , herpes zoster virus or Bacteroides gingivalis can actually overwhelm endothelial NO production and induce a disturbance in balance between endothelial relaxant and contractile factors. Such pathological condition is defined as an endothelial dysfunction (ED) and it represents the most important, although to some point reversible step in development of atherosclerosis149. In the fundamental nature of ED lies oxidative stress and all the above mentioned risk factors are capable to induce it.…”

“…The inhibition of NO synthesis leads to a shift in balance between endothelial relaxing and contractile factors in favour to autacoids with contractile action. Even though endothelium-dependent contraction is commonly present under physiological conditions, this process is much more pronounced in different pathological conditions associated with ED410.…”

“…ED associated with different pathological conditions include chronic heart failure, acute coronary syndrome, cardiac syndrome X, hypertension, impaired glucose tolerance (IGT), type 2 diabetes, obesity, peripheral artery disease (PAD), Behçet's disease, polycystic ovary syndrome, ankylosing spondylitis, subclinical hypothyroidism, chronic haemodialysis and hypertension or diabetes in pregnancy491314. Since ED may be a reversible process, there is an increased interest in investigation of different non-pharmacological and pharmacological methods that could improve endothelial function.…”

Endothelium Protective Function of Statins in Men and Women with Coronary Atherosclerosis

“…Изучению возможности коррекции ЭД с помощью лекарственной терапии уделяется большое внимание [8,9]. Особый интерес представляет изучение плейо-тропного эффекта статинов в части их влияния на со-судистый эндотелий [10,11].…”