The role of endothelium and its potential relationship in COPD and CVD. The dotted arrows in the figure indicate that the factors linking COPD and CVD are not yet fully understood and are likely to be interconnected through endothelial dysfunction. While the solid arrows represent the well-known risk factors for COPD and the mechanisms associated with endothelial dysfunction. Created with BioRender.com
Tanner L, Single AB. Animal models reflecting chronic obstructive pulmonary disease and related respiratory disorders: translating pre-clinical data into clinical relevance.J Innate Immun. 2020;12:203–25. [DOI] [PubMed] [PMC]
Martinez FJ, Donohue JF, Rennard SI. The future of chronic obstructive pulmonary disease treatment—difficulties of and barriers to drug development.Lancet. 2011;378:1027–37. [DOI] [PubMed]
GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015.Lancet. 2016;388:1459–544. [DOI] [PubMed] [PMC]
Vij N, Chandramani-Shivalingappa P, Van Westphal C, Hole R, Bodas M. Cigarette smoke-induced autophagy impairment accelerates lung aging, COPD-emphysema exacerbations and pathogenesis.Am J Physiol Cell Physiol. 2018;314:C73–87. [DOI] [PubMed] [PMC]
Hunninghake GM, Cho MH, Tesfaigzi Y, Soto-Quiros ME, Avila L, Lasky-Su J, et al. MMP12, lung function, and COPD in high-risk populations.N Engl J Med. 2009;361:2599–608. [DOI] [PubMed] [PMC]
Ding Z, Wang K, Li J, Tan Q, Tan W, Guo G. Association between glutathione S-transferase gene M1 and T1 polymorphisms and chronic obstructive pulmonary disease risk: a meta-analysis.Clin Genet. 2019;95:53–62. [DOI] [PubMed]
Huang X, Mu X, Deng L, Fu A, Pu E, Tang T, et al. The etiologic origins for chronic obstructive pulmonary disease.Int J Chron Obstruct Pulmon Dis. 2019;14:1139–58. [DOI] [PubMed] [PMC]
Moschino L, Bonadies L, Baraldi E. Lung growth and pulmonary function after prematurity and bronchopulmonary dysplasia.Pediatr Pulmonol. 2021;56:3499–508. [DOI] [PubMed] [PMC]
Sheikh K, Coxson HO, Parraga G. This is what COPD looks like.Respirology. 2016;21:224–36. [DOI] [PubMed]
Vogelmeier CF, Román-Rodríguez M, Singh D, Han MK, Rodríguez-Roisin R, Ferguson GT. Goals of COPD treatment: focus on symptoms and exacerbations.Respir Med. 2020;166:105938. [DOI] [PubMed]
Soler-Cataluña JJ, Martínez-García MA, Román Sánchez P, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease.Thorax. 2005;60:925–31. [DOI] [PubMed] [PMC]
Singh D, Agusti A, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease: the GOLD science committee report 2019.Eur Respir J. 2019;53:1900164. [DOI] [PubMed]
Barnes PJ, Celli BR. Systemic manifestations and comorbidities of COPD.Eur Respir J. 2009;33:1165–85. [DOI] [PubMed] [PMC]
Rabe KF, Hurst JR, Suissa S. Cardiovascular disease and COPD: dangerous liaisons?Eur Respir Rev. 2018;27:180057. [DOI] [PubMed] [PMC]
Polverino F, Celli BR, Owen CA. COPD as an endothelial disorder: endothelial injury linking lesions in the lungs and other organs? (2017 Grover Conference Series).Pulm Circ. 2018;8:2045894018758528. [DOI] [PubMed] [PMC]
Brightling C, Greening N. Airway inflammation in COPD: progress to precision medicine.Eur Respir J. 2019;54:1900651. [DOI] [PubMed]
Strzelak A, Ratajczak A, Adamiec A, Feleszko W. Tobacco smoke induces and alters immune responses in the lung triggering inflammation, allergy, asthma and other lung diseases: a mechanistic review.Int J Environ Res Public Health. 2018;15:1033. [DOI] [PubMed] [PMC]
Rouadi PW, Idriss SA, Naclerio RM, Peden DB, Ansotegui IJ, Canonica GW, et al. Immunopathological features of air pollution and its impact on inflammatory airway diseases (IAD).World Allergy Organ J. 2020;13:100467. [DOI] [PubMed] [PMC]
Gelfand EW, Joetham A, Wang M, Takeda K, Schedel M. Spectrum of T-lymphocyte activities regulating allergic lung inflammation.Immunol Rev. 2017;278:63–86. [DOI] [PubMed] [PMC]
Frangogiannis N. Transforming growth factor-β in tissue fibrosis.J Exp Med. 2020;217:e20190103. [DOI] [PubMed] [PMC]
Price DT, Loscalzo J. Cellular adhesion molecules and atherogenesis.Am J Med. 1999;107:85–97.
Barnes PJ. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease.J Allergy Clin Immunol. 2016;138:16–27. [DOI] [PubMed]
David B, Bafadhel M, Koenderman L, De Soyza A. Eosinophilic inflammation in COPD: from an inflammatory marker to a treatable trait.Thorax. 2021;76:188–95. [DOI] [PubMed] [PMC]
Mycroft K, Krenke R, Górska K. Eosinophils in COPD-current concepts and clinical implications.J Allergy Clin Immunol Pract. 2020;8:2565–74. [DOI] [PubMed]
Chatila WM, Thomashow BM, Minai OA, Criner GJ, Make BJ. Comorbidities in chronic obstructive pulmonary disease.Proc Am Thorac Soc. 2008;5:549–55. [DOI] [PubMed] [PMC]
Westerik JA, Metting EI, van Boven JF, Tiersma W, Kocks JW, Schermer TR. Associations between chronic comorbidity and exacerbation risk in primary care patients with COPD.Respir Res. 2017;18:31. [DOI] [PubMed] [PMC]
McGarvey LP, John M, Anderson JA, Zvarich M, Wise RA; TORCH Clinical Endpoint Committee. Ascertainment of cause-specific mortality in COPD: operations of the TORCH Clinical Endpoint Committee.Thorax. 2007;62:411–5. [DOI] [PubMed] [PMC]
André S, Conde B, Fragoso E, Boléo-Tomé JP, Areias V, Cardoso J; GI DPOC-Grupo de Interesse na Doença Pulmonar Obstrutiva Crónica. COPD and cardiovascular disease.Pulmonology. 2019;25:168–76. [DOI] [PubMed]
Austin V, Crack PJ, Bozinovski S, Miller AA, Vlahos R. COPD and stroke: are systemic inflammation and oxidative stress the missing links?Clin Sci (Lond). 2016;130:1039–50. [DOI] [PubMed] [PMC]
Morgan AD, Zakeri R, Quint JK. Defining the relationship between COPD and CVD: What are the implications for clinical practice?Ther Adv Respir Dis. 2018;12:1753465817750524. [DOI] [PubMed] [PMC]
Theodorakopoulou MP, Bakaloudi DR, Alexandrou ME, Papakosta D, Pataka A, Kioumis I, et al. Endothelial dysfunction during acute exacerbations of chronic obstructive pulmonary disease: a systematic review and meta-analysis.COPD. 2021;18:246–53. [DOI] [PubMed]
Goldenberg NM, Kuebler WM. Endothelial cell regulation of pulmonary vascular tone, inflammation, and coagulation.Compr Physiol. 2015;5:531–59. [DOI] [PubMed]
Green CE, Turner AM. The role of the endothelium in asthma and chronic obstructive pulmonary disease (COPD).Respir Res. 2017;18:20. [DOI] [PubMed] [PMC]
Kutcher ME, Herman IM. The pericyte: cellular regulator of microvascular blood flow.Microvasc Res. 2009;77:235–46. [DOI] [PubMed] [PMC]
Szucs B, Szucs C, Petrekanits M, Varga JT. Molecular characteristics and treatment of endothelial dysfunction in patients with COPD: a review article.Int J Mol Sci. 2019;20:4329. [DOI] [PubMed] [PMC]
Aird WC. Phenotypic heterogeneity of the endothelium: I. structure, function, and mechanisms.Circ Res. 2007;100:158–73. [DOI] [PubMed]
Laniado-Laborín R. Smoking and chronic obstructive pulmonary disease (COPD). Parallel epidemics of the 21st century.Int J Environ Res Public Health. 2009;6:209–24. [DOI] [PubMed]
Huertas A, Guignabert C, Barberà JA, Bärtsch P, Bhattacharya J, Bhattacharya S, et al. Pulmonary vascular endothelium: the orchestra conductor in respiratory diseases: highlights from basic research to therapy.Eur Respir J. 2018;51:1700745. [DOI] [PubMed]
Liebow AA. Pulmonary emphysema with special reference to vascular changes.Am Rev Respir Dis. 1959;80:67–93. [DOI] [PubMed]
Dinh-Xuan AT, Pepke-Zaba J, Butt AY, Cremona G, Higenbottam TW. Impairment of pulmonary-artery endothelium-dependent relaxation in chronic obstructive lung disease is not due to dysfunction of endothelial cell membrane receptors nor to L-arginine deficiency.Br J Pharmacol. 1993;109:587–91. [DOI] [PubMed] [PMC]
Peinado VI, Barbera JA, Ramirez J, Gomez FP, Roca J, Jover L, et al. Endothelial dysfunction in pulmonary arteries of patients with mild COPD.Am J Physiol. 1998;274:L908–13. [DOI] [PubMed]
Washko GR. The role and potential of imaging in COPD.Med Clin North Am. 2012;96:729–43. [DOI] [PubMed] [PMC]
Gane J, Stockley R. Mechanisms of neutrophil transmigration across the vascular endothelium in COPD.Thorax. 2012;67:553–61. [DOI] [PubMed]
Giavazzi R, Nicoletti MI, Chirivi RG, Hemingway I, Bernasconi S, Allavena P, et al. Soluble intercellular adhesion molecule-1 (ICAM-1) is released into the serum and ascites of human ovarian carcinoma patients and in nude mice bearing tumour xenografts.Eur J Cancer. 1994;30A:1865–70. [DOI] [PubMed]
Woolhouse IS, Bayley DL, Lalor P, Adams DH, Stockley RA. Endothelial interactions of neutrophils under flow in chronic obstructive pulmonary disease.Eur Respir J. 2005;25:612–7. [DOI] [PubMed]
Sorkness RL, Mehta H, Kaplan MR, Miyasaka M, Hefle SL, Lemanske RF Jr. Effect of ICAM-1 blockade on lung inflammation and physiology during acute viral bronchiolitis in rats.Pediatr Res. 2000;47:819–24. [DOI] [PubMed]
Johnston NW, Olsson M, Edsbäcker S, Gerhardsson de Verdier M, Gustafson P, McCrae C, et al. Colds as predictors of the onset and severity of COPD exacerbations.Int J Chron Obstruct Pulmon Dis. 2017;12:839–48. [DOI] [PubMed] [PMC]
Riise GC, Larsson S, Löfdahl CG, Andersson BA. Circulating cell adhesion molecules in bronchial lavage and serum in COPD patients with chronic bronchitis.Eur Respir J. 1994;7:1673–7. [DOI] [PubMed]
Garcia-Rio F, Miravitlles M, Soriano JB, Muñoz L, Duran-Tauleria E, Sánchez G, et al.; EPI-SCAN Steering Committee. Systemic inflammation in chronic obstructive pulmonary disease: a population-based study.Respir Res. 2010;11:63. [DOI] [PubMed] [PMC]
Faner R, Tal-Singer R, Riley JH, Celli B, Vestbo J, MacNee W, et al.; ECLIPSE Study Investigators. Lessons from ECLIPSE: a review of COPD biomarkers.Thorax. 2014;69:666–72. [DOI] [PubMed]
Wang Z, Locantore N, Haldar K, Ramsheh MY, Beech AS, Ma W, et al. Inflammatory endotype-associated airway microbiome in chronic obstructive pulmonary disease clinical stability and exacerbations: a multicohort longitudinal analysis.Am J Respir Crit Care Med. 2021;203:1488–502. [DOI] [PubMed] [PMC]
Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 Report. GOLD executive summary.Am J Respir Crit Care Med. 2017;195:557–82. [DOI] [PubMed]
Pantazopoulos I, Magounaki K, Kotsiou O, Rouka E, Perlikos F, Kakavas S, et al. Incorporating biomarkers in COPD management: the research keeps going.J Pers Med. 2022;12:379. [DOI] [PubMed] [PMC]
Heiman AS, Abonyo BO, Darling-Reed SF, Alexander MS. Cytokine-stimulated human lung alveolar epithelial cells release eotaxin-2 (CCL24) and eotaxin-3 (CCL26).J Interferon Cytokine Res. 2005;25:82–91. [DOI] [PubMed]
Henrot P, Prevel R, Berger P, Dupin I. Chemokines in COPD: from implication to therapeutic use.Int J Mol Sci. 2019;20:2785. [DOI] [PubMed] [PMC]
Ivanovska M, Abdi Z, Murdjeva M, Macedo D, Maes A, Maes M. CCL-11 or eotaxin-1: an immune marker for ageing and accelerated ageing in neuro-psychiatric disorders.Pharmaceuticals (Basel). 2020;13:230. [DOI] [PubMed] [PMC]
Wang LY, Tu YF, Lin YC, Huang CC. CXCL5 signaling is a shared pathway of neuroinflammation and blood-brain barrier injury contributing to white matter injury in the immature brain.J Neuroinflammation. 2016;13:6. [DOI] [PubMed] [PMC]
Miyake M, Goodison S, Urquidi V, Gomes Giacoia E, Rosser CJ. Expression of CXCL1 in human endothelial cells induces angiogenesis through the CXCR2 receptor and the ERK1/2 and EGF pathways.Lab Invest. 2013;93:768–78. [DOI] [PubMed]
Pavord ID, Lettis S, Locantore N, Pascoe S, Jones PW, Wedzicha JA, et al. Blood eosinophils and inhaled corticosteroid/long-acting β-2 agonist efficacy in COPD.Thorax. 2016;71:118–25. [DOI] [PubMed] [PMC]
Singh D, Kolsum U, Brightling CE, Locantore N, Agusti A, Tal-Singer R; ECLIPSE investigators. Eosinophilic inflammation in COPD: prevalence and clinical characteristics.Eur Respir J. 2014;44:1697–700. [DOI] [PubMed]
Siddiqui SH, Guasconi A, Vestbo J, Jones P, Agusti A, Paggiaro P, et al. Blood eosinophils: a biomarker of response to extrafine beclomethasone/formoterol in chronic obstructive pulmonary disease.Am J Respir Crit Care Med. 2015;192:523–5. [DOI] [PubMed] [PMC]
Aaron SD, Vandemheen KL, Maltais F, Field SK, Sin DD, Bourbeau J, et al. TNFα antagonists for acute exacerbations of COPD: a randomised double-blind controlled trial.Thorax. 2013;68:142–8. [DOI] [PubMed]
Pisi G, Olivieri D, Chetta A. The airway neurogenic inflammation: clinical and pharmacological implications.Inflamm Allergy Drug Targets. 2009;8:176–81. [DOI] [PubMed]
Walsh DA, McWilliams DF. Tachykinins and the cardiovascular system.Curr Drug Targets. 2006;7:1031–42. [DOI] [PubMed]
Barnes PJ. Neurogenic inflammation in the airways.Respir Physiol. 2001;125:145–54. [DOI] [PubMed]
Groneberg DA, Quarcoo D, Frossard N, Fischer A. Neurogenic mechanisms in bronchial inflammatory diseases.Allergy. 2004;59:1139–52. [DOI] [PubMed]
Sin DD, Anthonisen NR, Soriano JB, Agusti AG. Mortality in COPD: role of comorbidities.Eur Respir J. 2006;28:1245–57. [DOI] [PubMed]
Boukhenouna S, Wilson MA, Bahmed K, Kosmider B. Reactive oxygen species in chronic obstructive pulmonary disease.Oxid Med Cell Longev. 2018;2018:5730395. [DOI] [PubMed] [PMC]
Pryor WA, Stone K. Oxidants in cigarette smoke radicals, hydrogen peroxide, peroxynitrate, and peroxynitrite.Ann N Y Acad Sci. 1993;686:12–27. [DOI] [PubMed]
Yang SR, Chida AS, Bauter MR, Shafiq N, Seweryniak K, Maggirwar SB, et al. Cigarette smoke induces proinflammatory cytokine release by activation of NF-kappaB and posttranslational modifications of histone deacetylase in macrophages.Am J Physiol Lung Cell Mol Physiol. 2006;291:L46–57. [DOI] [PubMed]
Zuo L, He F, Sergakis GG, Koozehchian MS, Stimpfl JN, Rong Y, et al. Interrelated role of cigarette smoking, oxidative stress, and immune response in COPD and corresponding treatments.Am J Physiol Lung Cell Mol Physiol. 2014;307:L205–18. [DOI] [PubMed]
Walter DH, Rittig K, Bahlmann FH, Kirchmair R, Silver M, Murayama T, et al. Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells.Circulation. 2002;105:3017–24. [DOI] [PubMed]
Tejero J, Shiva S, Gladwin MT. Sources of vascular nitric oxide and reactive oxygen species and their regulation.Physiol Rev. 2019;99:311–79. [DOI] [PubMed] [PMC]
Zheng D, Liu J, Piao H, Zhu Z, Wei R, Liu K. ROS-triggered endothelial cell death mechanisms: focus on pyroptosis, parthanatos, and ferroptosis.Front Immunol. 2022;13:1039241. [DOI] [PubMed] [PMC]
Lv H, Zhen C, Liu J, Yang P, Hu L, Shang P. Unraveling the potential role of glutathione in multiple forms of cell death in cancer therapy.Oxid Med Cell Longev. 2019;2019:3150145. [DOI] [PubMed] [PMC]
Qin X, Zhang J, Wang B, Xu G, Yang X, Zou Z, et al. Ferritinophagy is involved in the zinc oxide nanoparticles-induced ferroptosis of vascular endothelial cells.Autophagy. 2021;17:4266–85. [DOI] [PubMed] [PMC]
Luo EF, Li HX, Qin YH, Qiao Y, Yan GL, Yao YY, et al. Role of ferroptosis in the process of diabetes-induced endothelial dysfunction.World J Diabetes. 2021;12:124–37. [DOI] [PubMed] [PMC]
Sheng S, Xu J, Liang Q, Hong L, Zhang L. Astragaloside IV inhibits bleomycin-induced ferroptosis in human umbilical vein endothelial cells by mediating LPC.Oxid Med Cell Longev. 2021;2021:6241242. [DOI] [PubMed] [PMC]
Wang Y, Kuang X, Yin Y, Han N, Chang L, Wang H, et al. Tongxinluo prevents chronic obstructive pulmonary disease complicated with atherosclerosis by inhibiting ferroptosis and protecting against pulmonary microvascular barrier dysfunction.Biomed Pharmacother. 2022;145:112367. [DOI] [PubMed]
Swanson KV, Deng M, Ting JP. The NLRP3 inflammasome: molecular activation and regulation to therapeutics.Nat Rev Immunol. 2019;19:477–89. [DOI] [PubMed] [PMC]
Abais JM, Xia M, Zhang Y, Boini KM, Li PL. Redox regulation of NLRP3 inflammasomes: ROS as trigger or effector?Antioxid Redox Signal. 2015;22:1111–29. [DOI] [PMC]
Wu Q, He X, Wu LM, Zhang RY, Li LM, Wu CM, et al. MLKL aggravates Ox-LDL-induced cell pyroptosis via activation of NLRP3 inflammasome in human umbilical vein endothelial cells.Inflammation. 2020;43:2222–31. [DOI] [PubMed]
Hang L, Peng Y, Xiang R, Li X, Li Z. Ox-LDL causes endothelial cell injury through ASK1/NLRP3-mediated inflammasome activation via endoplasmic reticulum stress.Drug Des Devel Ther. 2020;14:731–44. [DOI] [PubMed] [PMC]
Zhang Y, Chen Y, Zhang Y, Li PL, Li X. Contribution of cathepsin B-dependent Nlrp3 inflammasome activation to nicotine-induced endothelial barrier dysfunction.Eur J Pharmacol. 2019;865:172795. [DOI] [PubMed] [PMC]
Cau SB, Bruder-Nascimento A, Silva MB, Ramalho FNZ, Mestriner F, Alves-Lopes R, et al. Angiotensin-II activates vascular inflammasome and induces vascular damage.Vascul Pharmacol. 2021;139:106881. [DOI] [PubMed] [PMC]
Pouwels SD, Zijlstra GJ, van der Toorn M, Hesse L, Gras R, Ten Hacken NH, et al. Cigarette smoke-induced necroptosis and DAMP release trigger neutrophilic airway inflammation in mice.Am J Physiol Lung Cell Mol Physiol. 2016;310:L377–86. [DOI] [PubMed]
Wang Y, Zhou JS, Xu XC, Li ZY, Chen HP, Ying SM, et al. Endoplasmic reticulum chaperone GRP78 mediates cigarette smoke-induced necroptosis and injury in bronchial epithelium.Int J Chron Obstruct Pulmon Dis. 2018;13:571–81. [DOI] [PubMed] [PMC]
Mizumura K, Maruoka S, Shimizu T, Gon Y. Autophagy, selective autophagy, and necroptosis in COPD.Int J Chron Obstruct Pulmon Dis. 2018;13:3165–72. [DOI] [PubMed] [PMC]
Tchkonia T, Zhu Y, van Deursen J, Campisi J, Kirkland JL. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities.J Clin Invest. 2013;123:966–72. [DOI] [PubMed] [PMC]
Amsellem V, Gary-Bobo G, Marcos E, Maitre B, Chaar V, Validire P, et al. Telomere dysfunction causes sustained inflammation in chronic obstructive pulmonary disease.Am J Respir Crit Care Med. 2011;184:1358–66. [DOI] [PubMed]
Tsuji T, Aoshiba K, Nagai A. Alveolar cell senescence in patients with pulmonary emphysema.Am J Respir Crit Care Med. 2006;174:886–93. [DOI] [PubMed]
Rutten EP, Gopal P, Wouters EF, Franssen FM, Hageman GJ, Vanfleteren LE, et al. Various mechanistic pathways representing the aging process are altered in COPD.Chest. 2016;149:53–61. [DOI] [PubMed]
Birch J, Anderson RK, Correia-Melo C, Jurk D, Hewitt G, Marques FM, et al. DNA damage response at telomeres contributes to lung aging and chronic obstructive pulmonary disease.Am J Physiol Lung Cell Mol Physiol. 2015;309:L1124–37. [DOI] [PubMed] [PMC]
Borgas D, Chambers E, Newton J, Ko J, Rivera S, Rounds S, et al. Cigarette smoke disrupted lung endothelial barrier integrity and increased susceptibility to acute lung injury via histone deacetylase 6.Am J Respir Cell Mol Biol. 2016;54:683–96. [DOI] [PubMed] [PMC]
Ferrer E, Peinado VI, Castañeda J, Prieto-Lloret J, Olea E, González-Martín MC, et al. Effects of cigarette smoke and hypoxia on pulmonary circulation in the guinea pig.Eur Respir J. 2011;38:617–27. [DOI] [PubMed]
Paschalaki K, Rossios C, Pericleous C, MacLeod M, Rothery S, Donaldson GC, et al. Inhaled corticosteroids reduce senescence in endothelial progenitor cells from patients with COPD.Thorax. 2022;77:616–20. [DOI] [PubMed] [PMC]
Zeng M, Zhang X, Xing W, Wang Q, Liang G, He Z. Cigarette smoke extract mediates cell premature senescence in chronic obstructive pulmonary disease patients by up-regulating USP7 to activate p300-p53/p21 pathway.Toxicol Lett. 2022;359:31–45. [DOI] [PubMed]
Rivas M, Gupta G, Costanzo L, Ahmed H, Wyman AE, Geraghty P. Senescence: pathogenic driver in chronic obstructive pulmonary disease.Medicina (Kaunas). 2022;58:817. [DOI] [PubMed] [PMC]
Kasahara Y, Tuder RM, Cool CD, Lynch DA, Flores SC, Voelkel NF. Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema.Am J Respir Crit Care Med. 2001;163:737–44. [DOI] [PubMed]
Zeng H, Kong X, Zhang H, Chen Y, Cai S, Luo H, et al. Inhibiting DNA methylation alleviates cigarette smoke extract-induced dysregulation of Bcl-2 and endothelial apoptosis.Tob Induc Dis. 2020;18:51. [DOI] [PubMed] [PMC]
Henson PM, Vandivier RW, Douglas IS. Cell death, remodeling, and repair in chronic obstructive pulmonary disease?Proc Am Thorac Soc. 2006;3:713–7. [DOI] [PubMed] [PMC]
Farid M, Kanaji N, Nakanishi M, Gunji Y, Michalski J, Iwasawa S, et al. Smad3 mediates cigarette smoke extract (CSE) induction of VEGF release by human fetal lung fibroblasts.Toxicol Lett. 2013;220:126–34. [DOI] [PubMed]
Taraseviciene-Stewart L, Douglas IS, Nana-Sinkam PS, Lee JD, Tuder RM, Nicolls MR, et al. Is alveolar destruction and emphysema in chronic obstructive pulmonary disease an immune disease?Proc Am Thorac Soc. 2006;3:687–90. [DOI] [PubMed]
Zhang C, Cai S, Chen P, Chen JB, Wu J, Wu SJ. Inhibition of tumor necrosis factor-alpha reduces alveolar septal cell apoptosis in passive smoking rats.Chin Med J. 2008;121:597–601. [PubMed]
Kasahara Y, Tuder RM, Taraseviciene-Stewart L, Le Cras TD, Abman S, Hirth PK, et al. Inhibition of VEGF receptors causes lung cell apoptosis and emphysema.J Clin Invest. 2000;106:1311–9. [DOI] [PubMed] [PMC]
Segura-Valdez L, Pardo A, Gaxiola M, Uhal BD, Becerril C, Selman M. Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD.Chest. 2000;117:684–94. [DOI] [PubMed]
Yasuo M, Mizuno S, Kraskauskas D, Bogaard HJ, Natarajan R, Cool CD, et al. Hypoxia inducible factor-1α in human emphysema lung tissue.Eur Respir J. 2011;37:775–83. [DOI] [PubMed]
Lee SH, Lee SH, Kim CH, Yang KS, Lee EJ, Min KH, et al. Increased expression of vascular endothelial growth factor and hypoxia inducible factor-1α in lung tissue of patients with chronic bronchitis.Clin Biochem. 2014;47:552–9. [DOI] [PubMed]
Noe J, Petrusca D, Rush N, Deng P, VanDemark M, Berdyshev E, et al. CFTR regulation of intracellular pH and ceramides is required for lung endothelial cell apoptosis.Am J Respir Cell Mol Biol. 2009;41:314–23. [DOI] [PubMed] [PMC]
Petrache I, Fijalkowska I, Medler TR, Skirball J, Cruz P, Zhen L, et al. α-1 antitrypsin inhibits caspase-3 activity, preventing lung endothelial cell apoptosis.Am J Pathol. 2006;169:1155–66. [DOI] [PubMed] [PMC]
Rodriguez-Miguelez P, Seigler N, Bass L, Dillard TA, Harris RA. Assessments of endothelial function and arterial stiffness are reproducible in patients with COPD.Int J Chron Obstruct Pulmon Dis. 2015;10:1977–86. [DOI] [PubMed] [PMC]
Flammer AJ, Anderson T, Celermajer DS, Creager MA, Deanfield J, Ganz P, et al. The assessment of endothelial function: from research into clinical practice.Circulation. 2012;126:753–67. [DOI] [PubMed] [PMC]
Barr RG, Mesia-Vela S, Austin JH, Basner RC, Keller BM, Reeves AP, et al. Impaired flow-mediated dilation is associated with low pulmonary function and emphysema in ex-smokers: the Emphysema and Cancer Action Project (EMCAP) Study.Am J Respir Crit Care Med. 2007;176:1200–7. [DOI] [PubMed] [PMC]
Eickhoff P, Valipour A, Kiss D, Schreder M, Cekici L, Geyer K, et al. Determinants of systemic vascular function in patients with stable chronic obstructive pulmonary disease.Am J Respir Crit Care Med. 2008;178:1211–8. [DOI] [PubMed]
Marchetti N, Ciccolella DE, Jacobs MR, Crookshank A, Gaughan JP, Kashem MA, et al. Hospitalized acute exacerbation of COPD impairs flow and nitroglycerin-mediated peripheral vascular dilation.COPD. 2011;8:60–5. [DOI] [PubMed]
Clarenbach CF, Sievi NA, Kohler M. Annual progression of endothelial dysfunction in patients with COPD.Respir Med. 2017;132:15–20. [DOI] [PubMed]
Yang L, Mäki-Petäjä K, Cheriyan J, McEniery C, Wilkinson IB. The role of epoxyeicosatrienoic acids in the cardiovascular system.Br J Clin Pharmacol. 2015;80:28–44. [DOI] [PubMed] [PMC]
Maclay JD, McAllister DA, Mills NL, Paterson FP, Ludlam CA, Drost EM, et al. Vascular dysfunction in chronic obstructive pulmonary disease.Am J Respir Crit Care Med. 2009;180:513–20. [DOI] [PubMed]
Theodorakopoulou MP, Bakaloudi DR, Dipla K, Zafeiridis A, Boutou AK. Vascular endothelial damage in COPD: current functional assessment methods and future perspectives.Expert Rev Respir Med. 2021;15:1121–33. [DOI] [PubMed]
Berry CE, Wise RA. Mortality in COPD: causes, risk factors, and prevention.COPD. 2010;7:375–82. [DOI] [PubMed] [PMC]
Mannino DM, Thorn D, Swensen A, Holguin F. Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD.Eur Respir J. 2008;32:962–9. [DOI] [PubMed]
Yang Q, Underwood MJ, Hsin MK, Liu XC, He GW. Dysfunction of pulmonary vascular endothelium in chronic obstructive pulmonary disease: basic considerations for future drug development.Curr Drug Metab. 2008;9:661–7. [DOI] [PubMed]
Ye C, Younus A, Malik R, Roberson L, Shaharyar S, Veledar E, et al. Subclinical cardiovascular disease in patients with chronic obstructive pulmonary disease: a systematic review.QJM. 2017;110:341–9. [DOI] [PubMed]