No Independent Influence of Statins on the Chronic Obstructive Pulmonary Disease Exacerbation Rate: A Cohort Observation Study Over 10 Years

Yayan, Josef; Bald, Markus; Franke, KJ

doi:10.2147/ijgm.s309647

Cited by 6 publications

(8 citation statements)

References 34 publications

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“…However, clinical studies demonstrated a conflicting therapeutic effect of cholesterol reduction by statins on clinical phenomes and outcomes of patients with COPD. 33 , 34 , 35 It is still questioned whether the hypercholesterolemia can change lung epithelial cell sensitivity in response to external factors like smoking, accelerate epithelia‐driven local inflammation through hyper‐production of inflammatory mediators like cytokines, and contribute to metabolic disorders‐oriented organelle dysfunction like mitochondria. There is still a lack of direct evidence how external cholesterol induces the secondary accumulation of intra‐epithelial cholesterol and exacerbates the inflammation in the lung.…”

Section: Discussionmentioning

confidence: 99%

“…High level of cholesterol in plasma was found to predict complications, severities, stages and medication needs of patients with COPD. However, clinical studies demonstrated a conflicting therapeutic effect of cholesterol reduction by statins on clinical phenomes and outcomes of patients with COPD 33–35 . It is still questioned whether the hypercholesterolemia can change lung epithelial cell sensitivity in response to external factors like smoking, accelerate epithelia‐driven local inflammation through hyper‐production of inflammatory mediators like cytokines, and contribute to metabolic disorders‐oriented organelle dysfunction like mitochondria.…”

Section: Discussionmentioning

confidence: 99%

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Regulatory roles of external cholesterol in human airway epithelial mitochondrial function through STARD3 signalling

Liu

et al. 2022

Clinical & Translational Med

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Background Hypercholesterolemia is found in patients with chronic lung inflammation, during which airway epithelial cells play important roles in maintenance of inflammatory responses to pathogens. The present study aims at molecular mechanisms by which cholesterol changes airway epithelial sensitivity in response to smoking. Methods Human bronchial epithelial cells (HBEs) were stimulated with cigarette smoke extract (CSE) and mice were exposed to CS/lipopolysaccharide (LPS) as models in vitro and in vivo. Severe COPD patients and healthy volunteers were also enrolled and the level of cholesterol in plasma was detected by metabolomics. Filipin III and elisa kits were used to stain free cholesterol. Mitochondrial function was detected by mitotracker green, mitotracker green, and Seahorse. Mitochondrial morphology was detected by high content screening and electron microscopy. The mRNA and protein levels of mitochondrial dynamics‐related proteins were detected by RT‐qPCR and Western blot,respectively. BODIPY 493/503 was used to stain lipid droplets. Lipidomics was used to detect intracellular lipid components. The mRNA level of interleukin (IL)‐6 and IL‐8 were detected by RT‐qPCR. Results We found that the cholesterol overload was associated with chronic obstructive pulmonary disease (COPD) and airway epithelia‐driven inflammation, evidenced by hypercholesterolemia in patients with COPD and preclinical models, alteration of lipid metabolism‐associated genes in CSE‐induced airway epithelia and production of ILs. External cholesterol altered airway epithelial sensitivity of inflammation in response to CSE, through the regulation of STARD3‐MFN2 pathway, cholesterol re‐distribution, altered transport and accumulation of cholesterol, activities of lipid transport regulators and disorder of mitochondrial function and dynamics. MFN2 down‐regulation increased airway epithelial sensitivity and production of ILs after smoking, at least partially by injuring fatty acid oxidation and activating mTOR phosphorylation. Conclusions Our data provide new insights for understanding molecular mechanisms of cholesterol‐altered airway epithelial inflammation and for developing diagnostic biomarkers and therapeutic targets to improve patient outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Regulatory roles of external cholesterol in human airway epithelial mitochondrial function through STARD3 signalling

Liu

et al. 2022

Clinical & Translational Med

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“…However, the study data did not show the therapeutic benefit of statins in patients with moderate to severe COPD, and the benefit of statins in patients with COPD and CVD cannot be ruled out because patients with coronary heart disease were not included. A recent cohort observational study on the effect of statins on the acute exacerbation rate in COPD patients obtained similar results from the STATCOPE study, that is, statins had no effect on the exacerbation rate and mortality in COPD patients (96). The results of a recent systematic review evaluating the benefits and harms of statins compared with placebo in COPD patients showed that statin use can reduce CRP and IL-6 levels, but there were no significant gains in COPD mortality, exacerbation frequency, or lung function (97).…”

Section: Statinsmentioning

confidence: 67%

Analysis of pathogenesis and drug treatment of chronic obstructive pulmonary disease complicated with cardiovascular disease

Wan²,

Mao

2022

Front. Med.

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Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airflow limitation, and is associated with abnormal inflammatory responses in the lungs to cigarette smoke and toxic and harmful gases. Due to the existence of common risk factors, COPD is prone to multiple complications, among which cardiovascular disease (CVD) is the most common. It is currently established that cardiovascular comorbidities increase the risk of exacerbations and mortality from COPD. COPD is also an independent risk factor for CVD, and its specific mechanism is still unclear, which may be related to chronic systemic inflammation, oxidative stress, and vascular dysfunction. There is evidence that chronic inflammation of the airways can lead to destruction of the lung parenchyma and decreased lung function. Inflammatory cells in the airways also generate reactive oxygen species in the lungs, and reactive oxygen species further promote lung inflammation through signal transduction and other pathways. Inflammatory mediators circulate from the lungs to the whole body, causing intravascular dysfunction, promoting the formation and rupture of atherosclerotic plaques, and ultimately leading to the occurrence and development of CVD. This article reviews the pathophysiological mechanisms of COPD complicated by CVD and the effects of common cardiovascular drugs on COPD.

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“…However, to date, there is no unequivocal answer on the effectiveness of statins in COPD patients. The use of statins is characterized by different effects on mortality rates and on exacerbations in COPD [ 97 , 98 , 100 , 101 , 102 , 103 , 104 , 105 ]. However, the prescription of statins has a justified value in many clinical situations, given the frequent combination of COPD with cardiovascular diseases of atherosclerotic genesis.…”

Section: Clinical Links Between Hdl and Copdmentioning

confidence: 99%

High-Density Lipoproteins: A Role in Inflammation in COPD

Kotlyarov

2022

IJMS

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Chronic obstructive pulmonary disease (COPD) is a widespread disease associated with high rates of disability and mortality. COPD is characterized by chronic inflammation in the bronchi as well as systemic inflammation, which contributes significantly to the clinically heterogeneous course of the disease. Lipid metabolism disorders are common in COPD, being a part of its pathogenesis. High-density lipoproteins (HDLs) are not only involved in lipid metabolism, but are also part of the organism’s immune and antioxidant defense. In addition, HDL is a versatile transport system for endogenous regulatory agents and is also involved in the removal of exogenous substances such as lipopolysaccharide. These functions, as well as information about lipoprotein metabolism disorders in COPD, allow a broader assessment of their role in the pathogenesis of heterogeneous and comorbid course of the disease.

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No Independent Influence of Statins on the Chronic Obstructive Pulmonary Disease Exacerbation Rate: A Cohort Observation Study Over 10 Years

Cited by 6 publications

References 34 publications

Regulatory roles of external cholesterol in human airway epithelial mitochondrial function through STARD3 signalling

Regulatory roles of external cholesterol in human airway epithelial mitochondrial function through STARD3 signalling

Analysis of pathogenesis and drug treatment of chronic obstructive pulmonary disease complicated with cardiovascular disease

High-Density Lipoproteins: A Role in Inflammation in COPD

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