Air Pollution-Induced Vascular Dysfunction: Potential Role of Endothelin-1 (ET-1) System

Abstract

Exposure to air pollution negatively impacts cardiovascular health. Studies show that increased exposure to a number of airborne pollutants increases the risk for cardiovascular disease progression, myocardial events, and cardiovascular mortality. A hypothesized mechanism linking air pollution and cardiovascular disease is the development of systemic inflammation and endothelium dysfunction, the latter of which can result from an imbalance of vasoactive factors within the vasculature. Endothelin-1 (ET-1) is a potent peptide vasoconstrictor that plays a significant role in regulating vascular homeostasis. It has been reported that the production and function of ET-1 and its receptors are upregulated in a number of disease states associated with endothelium dysfunction including hypertension and atherosclerosis. This mini-review surveys epidemiological and experimental air pollution studies focused on ET-1 dysregulation as a plausible mechanism underlying the development of cardiovascular disease. Although alterations in ET-1 system components are observed in some studies, there remains a need for future research to clarify whether these specific changes are compensatory or causally related to vascular injury and dysfunction. Moreover, further research may test the efficacy of selective ET-1 pharmacological interventions (e.g., ETA receptor inhibitors) to determine whether these treatments could impede the deleterious impact of air pollution exposure on cardiovascular health.

Apelin‑13 ameliorates metabolic and cardiovascular disorders in a rat model of type 2 diabetes with a high‑fat diet

“…the endothelium, cardiomyocytes, vascular smooth muscle cells, fibroblasts, leukocytes and macrophages (31). ET-1, which is a potent peptide vasoconstrictor with proinflammatory and profibrotic properties, participates in the development of diabetic vasculopathy via regulation of vascular homeostasis (30,32,33). NO is important in various physiological processes.…”

Atmen: Luftschadstoffe und Gesundheit – Teil III

“…Sowohl durch die unmittelbare Interaktion von Partikeln oder deren löslichen Bestandteilen, die über die Lunge in die Blutbahn gelangen, als auch durch die systemische Verfügbarkeit von Entzündungsmediatoren und ROS kann die vaskuläre Homöostase, insbesondere die Endothelfunktion, beeinträchtigt werden. Die endotheliale Dysfunktion äußert sich in vermehrter Vasokonstriktion aufgrund verminderter Bioverfügbarkeit von vasodilatorisch wirksamen NO und einem aktivierten, vasokonstriktorisch wirkenden Endothelin-1-System [127,153,164,165]. Diese Wirkungen werden als grundlegende pathophysiologische Mechanismen für erhöhte Blutdruckwerte oder eine eingeschränkte vaskuläre Regulation bei Luftschadstoffexposition angesehen.…”

Gestational nanomaterial exposures: microvascular implications during pregnancy, fetal development and adulthood

“…The formation of a hostile gestational environment, not only in the confines of physical growth restriction, but also with respect to limited resources or nutrients, has been a cornerstone of the Barker hypothesis, specifically with respect to the adult development of cardiovascular disease (Barker, 1990;Barker & Martyn, 1992). Increased maternal vascular contractility, also described in air pollution studies (Finch & Conklin, 2015), in combination with a reduced response to endothelium-dependent andindependent agonists characterize the founding cardiovascular alterations necessary for the development of a hostile gestational environment (Stapleton et al 2013;Vidanapathirana et al 2014a,b).…”

“…Endothelin-1 VEGF Braunig et al 2015Singh et al 2001Finch & Conklin, 2015Qi et al 2014 deposit within a variety of developing fetal tissues. As it is unclear if these particles may become sequestered, remain dormant, interrupt cellular signalling-receptor activity, or become a source of inflammation/reactive stressors, the physiological outcomes and long-term consequences have yet to be identified.…”

“…Groups have also begun to explore alterations associated with normal cellular function, communication, or signalling. In these cases, alterations to Rho-kinase and Endothelin-1 signalling have been identified as a possible mechanism contributing to vascular dysfunction (Singh et al 2001;Vidanapathirana et al 2014a,b;Thompson et al 2014;Finch & Conklin, 2015).…”