Cardiovascular Toxicology

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

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

Article

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.

Keywords

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

Abbreviations

Akt

Protein kinase B

Ca2+

Calcium

CAP

Concentrated ambient air particulate matter

CIMT

Carotid intima media thickness

cGMP

Cyclic guanosine monophosphate

COPD

Chronic obstructive pulmonary disease

CRP

C-reactive protein

CVD

Cardiovascular disease

DBP

Diastolic blood pressure

DE

Diesel exhaust

EC

Endothelial cell

ECE

Endothelin-converting enzyme

ECM

Extra cellular matrix

eNOS

Endothelial nitric oxide synthase

EPCs

Endothelial progenitor cells

ERK

Extracellular signal-regulated kinases

ET-1

Endothelin-1

ETA

Endothelin receptor A

ETB

Endothelin receptor B

ETB1

Endothelin receptor B1

FBF

Forearm blood flow

FMD

Flow-mediated dilation

GEE

Gasoline engine exhaust

HbA1c

Glycated hemoglobin

HO-1

Heme oxygenase 1

HRV

Heart rate variability

HTN

Hypertension

IL

Interleukin

InR

Insulin receptor

IR

Insulin resistance

MAPK

Mitogen-activated protein kinase

MI

Myocardial infarction

MMP

Matrix metalloproteinase

NMD

Endothelial-independent nitroglycerin-mediated dilatation

NO

Nitric oxide

O3

Ozone

PGE2

Prostaglandin E2

PI3K

Phosphoinositide 3-kinase

PKC

Protein kinase C

PKG

Protein kinase G

PM

Particulate matter

ROS

Reactive oxygen species

SBP

Systolic blood pressure

SGC

Soluble guanylyl cyclase

SHS

Secondhand smoke

SMC

Smooth muscle cell

T2D

Type 2 diabetes

TIMP-2

TIMP metallopeptidase inhibitor 2

TNFα

Tumor necrosis factor-α

VEGF

Vascular endothelial growth factor

VR

VEGF receptor

VSMC

Vascular smooth muscle cell

WHO

World Health Organization

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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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