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Review
. 2021 Aug 27:8:704106.
doi: 10.3389/fcvm.2021.704106. eCollection 2021.

Smoking and the Pathophysiology of Peripheral Artery Disease

Weiming Wang  1   2   3 , Tingting Zhao  1 , Kang Geng  1 , Gang Yuan  1 , Yue Chen  4 , Youhua Xu  1
Affiliations
Review

Smoking and the Pathophysiology of Peripheral Artery Disease

Weiming Wang et al. Front Cardiovasc Med. .

Abstract

Smoking is one of the most important preventable factors causing peripheral artery disease (PAD). The purpose of this review is to comprehensively analyze and summarize the pathogenesis and clinical characteristics of smoking in PAD based on existing clinical, in vivo, and in vitro studies. Extensive searches and literature reviews have shown that a large amount of data exists on the pathological process underlying the effects of cigarette smoke and its components on PAD through various mechanisms. Cigarette smoke extracts (CSE) induce endothelial cell dysfunction, smooth muscle cell remodeling and macrophage phenotypic transformation through multiple molecular mechanisms. These pathological changes are the molecular basis for the occurrence and development of peripheral vascular diseases. With few discussions on the topic, we will summarize recent insights into the effect of smoking on regulating PAD through multiple pathways and its possible pathogenic mechanism.

Keywords: clinical evidence; molecular mechanism; peripheral artery disease; review; smoking.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Smoking and peripheral artery disease. Different types of smoking may cause peripheral vascular diseases, such as arteriosclerosis, thromboangiitis obliterans, and abdominal aortic aneurysm. The ingredients in different cigarettes and substitutes are different, but they may all pose a risk of cardiovascular disease.
Figure 2
Figure 2
Smoking can cause atherosclerosis. Smoking can cause endothelial cell dysfunction, monocyte differentiation into macrophages and eventually foam cells, smooth muscle cell proliferation, migration and phenotypic transformation, and extracellular matrix degradation and remodeling. These processes are typically mediated by oxidative stress and inflammation.
Figure 3
Figure 3
Endothelial cell dysfunction caused by smoking and its mechanism. Smoking causes endothelial cell dysfunction through various pathways. The most important pathway is the decrease in NO synthesis due to eNOS deficiency and the reduction in eNOS function, which plays an important regulatory role in endothelial dysfunction.
Figure 4
Figure 4
Smoking affects the activity of eNOS by direct or indirect action (Red arrow: point of action). Inhibit GTPCH and reduce the synthesis of BH4; Promote the conversion of BH4 to BH2 through oxidative stress; Inhibit DHFR and reduce the conversion of BH2 to BH4;, ⑤ Prevent the combination of BH4 and eNOS to form a stable dimer; ⑥ Inhibit the conversion of L-Arg to NO; ⑦ Inhibit the activity of eNOS; ⑧ Promote the dissociation of Zn2+ from the dimer.
Figure 5
Figure 5
Smoking alters the function and phenotype of smooth muscle cells. Smoking induces smooth muscle cell autophagy through oxidative stress and causes smooth muscle cell proliferation and migration through multiple signaling pathways. At the same time, it also regulates changes in the functions of smooth muscle cells by stimulating macrophages to secrete exosomes.
See this image and copyright information in PMC

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