ISSN (Online) : 2277-4572



Author(s): Tamás Fischer

The endothelial system assures unhindered functioning and stability of the internal milieu maintaining vascular health and protecting against vascular injury, noxa. by producing, synthesising and excreting various substances: vasodilators and vasoconstrictors, growth factors and their inhibitors, pro-inflammatory and antiinflammatory agents, pro-thrombotic and fibrinolytic factors, and by keeping them in a strict equilibrium: endothelial dysfunction is the change of these properties, what is inappropriate with regard to the preservation of organ function ("endothelial dysfunction" has been used to define diverse syndromes characterized by changes in distinct endothelial functions, related to a cellular phenotypic switch from a quiescent to an activated state and this multifaceted disorder actually encompasses a spectrum of disturbances in vasomotor responses, antithrombogenic properties, vascular permeability, leukocyte recruitment [inflammation!] and endothelial cell proliferation [remodelling]). In the genesis and later development of chronic vascular injury/vasculopathy (e.g. atherosclerose) endothelial dysfunction (ED) has a crucial key role. The so called risk factors lead to vascular injury through the same mechanism of actions, by inducing oxidative stress (OS → ED!): Harm (noxa, i.e. isk factors [RFs]) → oxidative stress [OS] → endothelial activation [EA], endothlial dysfunction [ED], respectively → vacular injury, vascular disease). Under physiological conditions free radicals are generated during mitochondrial oxidative metabolism: The walls of the mitochondria are leaky to oxygen radicals produced during metabolism. 1% of oxygen used in respiration actually leaks from the mitochondria in the form of superoxide, but in older subjects, and/or in pathological states, in case of risk facor’s existence (i. e., repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic foreign impacts/disturbing influences/noxious effects!), respectively the proportion is greater: it exposes the cellular constituents to internally generated oxidative attack. As a part of the host defense response, any kind of noxa including the risk factors endangering steadiness of homeostasis start/trigger off an defensive chain founded on increased ROS formation (permanently existing/repeating noxa→persistent/lasting increased ROS formation→oxidative stress→endothelial activation, endothelial dysfunction, respectively → |chronic| vascular injury). The difference between normal host defense and detrimental cellular activation may well be a consequence of the nature, extent, duration, and combination of the proinflammatory stimuli: a profound but transient reduction of endotheliumdependent dilatation may be adaptive and not necessarily pro-vasculopathoghenic, but could become so if other adverse environmental conditions are also present, or if the foreign/unaccustomed stimuli become stable/permanent/lasting, respectivly. Wall of blood vessels may be triggered by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic influences-impacts-stimuli (noxa), against which protracted response, the so-called host defense response may develop, and in consequence of this, vascular damage pathological consecutive changes ending in vascular injury , ultimately, may develop. Recovery of endothelial function occurs in response to strategies known to reduce cardiovascular events: this adds support to the concept that restoration of endothelial function can restabilize the chronic vascular disease process. (I) Non-medicinal influencing of vascular endothelial dysfunction (ED), the lifestyle modifications, respestively, is of indispensable importance. Lifestyle risk factors modifications, including (1) smoking, (2) dietary habits (prescribing flavonoids, omega-3 long-chain polyunsaturated fatty acids (LCPUFAs), management of dietary GI), (3) modification of physical inactivity, (4) adiposity, (5) prescribing caloric restriction (CR), (6) eliminaion/discontinuance of the stressful lifestyle, strongly influence the established vascular risk factors, and also affect novel pathways of risk such as inflammation/oxidative stress, endothelial function, thrombosis/coagulation, and modest alterations of these lifestyle risk factors are achievable and have substantial effects on (cardio)vascular risk. (II) Medical treatment/influencing of vascular endothelial dysfunction (1) the RAAS-inhibiting angiotensin converting enzyme ihibitors and (2) angiotensinreceptor blockers |AT1 receptor blocker telmisartan included|; (3) direct renin inhibitors; (4) statins; (5) acetylsalicylic acid; (6) trimetazidin; (7) third generation beta blockers; (8) PPARgamma agonist; (9) folate; (10) vitamin D; (11) “causal” AOVs; (12) melatonin; (13) AGE crosslink breakers alagebrium; (14) ET receptor antagonist, bosentan; (15) coenzyme Q10;]; (16) the „causal” antioxidant, (17) N-acetyl-cysteine, (18) treprostinil, (19) selectin inhibitors, (20) melatonin (21) resveratrol, (22) L-arginine, (23) 5-HT(1A) receptor agonists 8-Oh DPAT, (24) TNF-α blockers have beneficial in ED also exert a favourable effect on all vesselés of the human organism/body; (III) We should strive to completely eliminate the risk factors of of the CV disease which induce OS and consequential ED, in addition.- In the end, let me point out that although pharmacoceutical interventions to delay vascular injury/events show promise, the main interventions that could be recommended now to human on the basis of evidence is the therapeutic lifestyle interventions.