Cardiovascular Toxicology

, Volume 16, Issue 3, pp 260–275 | Cite as

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

  • Jordan Finch
  • Daniel J. Conklin


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.


Air pollution Cardiovascular disease Endothelin-1 Endothelium dysfunction ET-1 Vascular dysfunction Vasoconstriction 



Protein kinase B




Concentrated ambient air particulate matter


Carotid intima media thickness


Cyclic guanosine monophosphate


Chronic obstructive pulmonary disease


C-reactive protein


Cardiovascular disease


Diastolic blood pressure


Diesel exhaust


Endothelial cell


Endothelin-converting enzyme


Extra cellular matrix


Endothelial nitric oxide synthase


Endothelial progenitor cells


Extracellular signal-regulated kinases




Endothelin receptor A


Endothelin receptor B


Endothelin receptor B1


Forearm blood flow


Flow-mediated dilation


Gasoline engine exhaust


Glycated hemoglobin


Heme oxygenase 1


Heart rate variability






Insulin receptor


Insulin resistance


Mitogen-activated protein kinase


Myocardial infarction


Matrix metalloproteinase


Endothelial-independent nitroglycerin-mediated dilatation


Nitric oxide




Prostaglandin E2


Phosphoinositide 3-kinase


Protein kinase C


Protein kinase G


Particulate matter


Reactive oxygen species


Systolic blood pressure


Soluble guanylyl cyclase


Secondhand smoke


Smooth muscle cell


Type 2 diabetes


TIMP metallopeptidase inhibitor 2


Tumor necrosis factor-α


Vascular endothelial growth factor


VEGF receptor


Vascular smooth muscle cell


World Health Organization



The authors thank the University of Louisville School of Medicine Integrated Programs in Biomedical Sciences for academic and financial support. We thank Natasha DeJarnett, PhD, MPH, for her editorial input. This work was supported by NIH Grants (ES019217, GM0103492, HL089083).


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© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Pharmacology and Toxicology, School of MedicineUniversity of LouisvilleLouisvilleUSA
  2. 2.Division of Cardiovascular Medicine, Department of Medicine, Diabetes and Obesity CenterUniversity of LouisvilleLouisvilleUSA

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