Cigarette
smoke exposure is well known to cause cardiovascular and airway diseases, both of which are leading causes of death and disability in the world. However, the molecular mechanisms that link cigarette
smoke to cardiovascular and airway diseases are not fully understood. Vascular and airway hyper-reactivity plays an important role in the pathogenesis of cardiovascular and airway diseases. Recent studies have demonstrated that
endothelin receptor up-regulation mediates vascular and airway hyper-reactivity in response to
endothelin-1 (ET-1,
endothelin receptor agonist) in cardiovascular and airway diseases. In the vasculature and airways, the main functional consequences of up-regulated
endothelin receptors by cigarette
smoke exposure are enhanced contraction and proliferation of the smooth muscle cells, which subsequently result in abnormal contraction (
spasm) and adverse proliferation (remodeling) of the vasculature and airways. The structural alteration by adverse remodeling involves changes in cell growth, cell death, cell migration, and production or degradation of the extracellular matrix. This review focuses on cigarette
smoke exposure that induces activation of intracellular
mitogen-activated protein kinase (MAPK) and subsequently results in the up-regulation of
endothelin receptors in the vasculature and airways, which mediates vascular and airway hyper-reactivity, one of the important pathogenic characteristics of cardiovascular and airway diseases. Understanding the molecular mechanisms of how cigarette
smoke causes up-regulation of
endothelin receptors in the vasculature and airways may provide new strategies for the treatment of cigarette
smoke-associated cardiovascular and
lung diseases.