Cpt1a alleviates cigarette smoke‑induced chronic obstructive pulmonary disease

Abstract

The current study aimed to determine the expression of carnitine palmitoyltransferase 1A (Cpt1a) in the lung tissue of chronic obstructive pulmonary disease (COPD) patients and its correlation with lung function. An increase in Cpt1a expression improved lung function in patients with COPD by inhibiting apoptosis and the inflammatory response of lung endothelial cells. Lung tissues of 20 patients with COPD and 10 control patients were collected, their Cpt1a expression was determined by western blotting and apoptosis and inflammation were assessed by haematoxylin-eosin staining, TUNEL assay and ELISA. Mice with knockout or overexpression of Cpt1a were constructed by lentivirus in vivo. A COPD model was induced by cigarette smoke and the role of Cpt1a in COPD was determined in vivo and in vitro. Cpt1a expression was positively correlated with lung function and negatively correlated with apoptosis and inflammation. Patients with COPD with higher expression of Cpt1a in lung tissues had improved lung function indices and lung tissue morphology with less apoptosis and decreased inflammatory response. Compared with the control group, COPD mice with Cpt1a knockdown had aggravated lung dysfunction and increased lung inflammation and apoptosis. Overexpression of Cpt1a alleviated lung dysfunction and reduced inflammatory response and apoptosis of lung tissues in COPD mice. Pulmonary microvascular endothelial cells of mice were isolated in vitro and the results were consistent with the findings obtained in vivo. In conclusion, the clinical, in vivo and in vitro data confirmed for the first time that Cpt1a alleviated lung dysfunction of patients with COPD by inhibiting apoptosis of endothelial cells and inflammatory responses.

Cigarette Smoke Exposure and microRNA in Human Alveolar Macrophages: A Pilot Study

“…Finally, to assess the potential interconnection of miRNAs in lung response to CS, we performed in silico prediction of hsa-miR target genes. Bioinformatic results revealed that the miRNAs analyzed may potentially be involved in the regulation of several inflammation driver genes, such as ATG14, BCL2, CPT1A, FOXC1, HAS2, HSPA1A, LAMTOR1, MCL1, MFN2, SCAMP5, SENP1, SOCS5, TGFBR2 and VEGFA, which are involved in immune system regulatory pathways [74][75][76][77][78][79][80][81][82][83][84][85][86][87]. Since several authors have experimentally…”

Evaluation of the Relationship Between the Balance of Carnitine Fractions and No(ii) Metabolites in Heart Tissue Under Conditions of L-Name-Induced Nitrogen Oxide Synthesis Deficiency in Rats

“…Наряду с этим, данные многочисленных экспериментальных работ демонстрируют такие свойства L-карнитина как антиоксидантный эффект [1,2,[8][9][10][11], возможность коррекции эндотелиальной дисфункции [8][9][10][11][12], влияние на процессы апоптоза и воспаления в различных тканях [11][12][13]. Механизмы описанных эффектов L-карнитина до настоящего времени остаются неясными.…”

“…В этой связи представляется интересной концепция карнитинового гомеостаза S. ранее предложенная S. Sharma и соавторами, которая связывает содержание L-карнитина, его ацильных производных и активность карнитинпальмитоилтрансфераз с NO (II) опосредованной передачей сигналов и функцией митохондрий в клетках эндотелия легочной артерии [11]. Эта взаимосвязь подтверждается в более поздних работах связанных с эндотелиальной дисфункцией на фоне диабета, однако исследование этой связи в других органах остается малоизученным, что и стало целью текущей работы [10][11][12][13].…”