Cigarette Smoke Directly Promotes Pulmonary Arterial Remodeling and Kv7.4 Channel Dysfunction.
Am J Respir Crit Care Med
; 203(10): 1290-1305, 2021 05 15.
Article
em En
| MEDLINE
| ID: mdl-33306938
ABSTRACT
Rationale Cigarette smoke is considered the chief leading cause of chronic obstructive pulmonary disease (COPD). Its impact on the progressive deterioration of airways has been extensively studied, but its direct effects on the pulmonary vasculature are less known. Objectives:
To prove that pulmonary arterial remodeling in patients with COPD is not just a consequence of alveolar hypoxia but also due to the direct effects of cigarette smoke on the pulmonary vascular bed.Methods:
We have used different molecular and cell biology approaches, as well as traction force microscopy, wire myography, and patch-clamp techniques in human cells and freshly isolated pulmonary arteries. In addition, we relied on in vivo models and human samples to analyze the effects of cigarette smoke on pulmonary vascular tone alterations. Measurements and MainResults:
Cigarette smoke extract exposure directly promoted a hypertrophic, senescent phenotype that in turn contributed, through the secretion of inflammatory molecules, to an increase in the proliferative potential of nonexposed cells. Interestingly, these effects were significantly reversed by antioxidants. Furthermore, cigarette smoke extract affected cell contractility and dysregulated the expression and activity of the voltage-gated K+ channel Kv7.4. This contributed to the impairment of vasoconstriction and vasodilation responses. Most importantly, the levels of this channel were diminished in the lungs of smoke-exposed mice, smokers, and patients with COPD.Conclusions:
Cigarette smoke directly contributes to pulmonary arterial remodeling through increased cell senescence, as well as vascular tone alterations because of diminished levels and function in the Kv7.4 channel. Strategies targeting these pathways may lead to novel therapies for COPD.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Artéria Pulmonar
/
Fumar
/
Doença Pulmonar Obstrutiva Crônica
/
Canais de Potássio KCNQ
/
Remodelação Vascular
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article