Alpha1-antitrypsin deficiency and cardiovascular disease: questions and issues of a debated relation.
Journal
Journal of cardiovascular medicine (Hagerstown, Md.)
ISSN: 1558-2035
Titre abrégé: J Cardiovasc Med (Hagerstown)
Pays: United States
ID NLM: 101259752
Informations de publication
Date de publication:
01 10 2022
01 10 2022
Historique:
entrez:
13
9
2022
pubmed:
14
9
2022
medline:
16
9
2022
Statut:
ppublish
Résumé
Alpha1-antitrypsin (AAT) is one of the major inhibitors involved in protease/antiprotease homeostasis, and it is mainly produced by hepatocytes and pulmonary epithelial cells. Its deficiency, called alpha1-antitrypsin deficit (AATD), leads to severe hepatic and respiratory issues. Also, AAT is released into the bloodstream providing systemic anti-inflammatory effects. Apart from acting as an acute-phase anti-inflammatory protein, it can be a biomarker for monitoring disease evolution. A reduced or defective production leads to a loss of anti-inflammatory function, protease-antiprotease imbalance and cellular engorgement due to polymers deposition, with system-wide repercussions. This review aims to evaluate AATD condition in the major vessels of the head and neck, thoracic and abdominal districts. Also, a dedicated focus on autoimmune vascular diseases will be provided. A critical revision of the main literature findings starting from the 1980s until now has been performed. Studies conducted over the years have provided several contradictory pieces of evidence. Most authors acknowledge the protective and anti-inflammatory AAT role on the vascular endothelium. However, correlations between AATD and major arteries, cerebral and cardiovascular conditions, and autoimmune diseases remain unclear. Most studies recognize the role of AATD in vascular diseases but only as a cofactor inducing cellular and tissue structure impairments. However, this condition alone is not enough to determine new disease onset. Due to the opposing results reported over the years, there is still a considerable lack of knowledge on the role covered by AATD in vascular diseases. A renewed interest in this research field should be encouraged to grant new solid evidence and validate the putative role of AATD screening and replacement therapy as useful diagnostic and treatment tools.
Identifiants
pubmed: 36099070
doi: 10.2459/JCM.0000000000001369
pii: 01244665-202210000-00001
doi:
Substances chimiques
Protease Inhibitors
0
alpha 1-Antitrypsin
0
Peptide Hydrolases
EC 3.4.-
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
637-645Informations de copyright
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Italian Federation of Cardiology.
Références
Kelly E, Greene CM, Carroll TP, McElvaney NG, O’Neill SJ. Alpha-1 antitrypsin deficiency. Respir Med 2010; 104:763–772.
Janciauskiene S, Welte T. Well known and less well known functions of alpha-1 antitrypsin: its role in chronic obstructive pulmonary disease and other disease developments. Ann Am Thorac Soc 2016; 13: (Suppl 4): S280–S288.
Pini L, Tiberio L, Arici M, et al. Z-alpha 1-antitrypsin polymers and small airways disease: a new paradigm in alfa-1 antitrypsin deficiency-related COPD development? Monaldi Arch Chest Dis 2021; 91:489–493.
Pini L, Paoletti G, Heffler E, et al. on behalf of Asthma and Alpha 1-Antitrypsin Research Group. Alpha 1-antitrypsin deficiency and asthma. Curr Opin Allergy Clin Immunol 2021; 21:46–51.
Pini L, Tiberio L, Venkatesan N, et al. The role of bronchial epithelial cells in the pathogenesis of COPD in Z-alpha 1 antitrypsin deficiency. Respir Res 2014; 15:112.
Marengoni A, Nicosia F, Tantucci C, Pini L, Grassi V. Heart and lung in the old age. The association between COPD and cardiovascular diseases: how much and how. Rass Patol Appar Resp 2011; 26:290–297.
Janciauskiene SM, Bals R, Koczulla R, Vogelmeier C, Köhnlein T, Welte T. The discovery of α1-antitrypsin and its role in health and disease. Respir Med 2011; 105:1129–1139.
Vila N, Millán M, Ferrer X, Riutort N, Escudero D. Levels of alpha 1-antitrypsin in plasma and risk of spontaneous cervical artery dissections: a case-control study. Stroke 2003; 34:E168–E169.
Grond-Ginsbach C, Engelter S, Werner I, et al. Alpha-1-antitrypsin deficiency alleles are not associated with cervical artery dissections. Neurology 2004; 62:1190–1192.
Konrad C, Langer C, Müller GA, et al. Protease inhibitors in spontaneous cervical artery dissections. Stroke 2005; 36:9–13.
Schievink WI, Björnsson J, Parisi JE, Prakash UB. Arterial fibromuscular dysplasia associated with severe alpha 1-antitrypsin deficiency. Mayo Clin Proc 1994; 69:1040–1043.
Baker CJ, Fiore A, Connolly ES Jr, Baker KZ, Solomon RA. Serum elastase and alpha-1-antitrypsin levels in patients with ruptured and unruptured cerebral aneurysms. Neurosurgery 1995; 37:56–61. discussion 61–62.
Schievink WI, Katzmann JA, Piepgras DG, Schaid DJ. Alpha-1-antitrypsin phenotypes among patients with intracranial aneurysms. J Neurosurg 1996; 84:781–784.
Yoneyama T, Kasuya H, Akagawa H, et al. Absence of alpha-1 antitrypsin deficiency alleles (S and Z) in Japanese and Korean patients with aneurysmal subarachnoid hemorrhage. Stroke 2004; 35:e376–e378.
Tyagi G, Srinivas D, Nanjaiah ND, et al. Gene expression in intracranial aneurysms-comparison analysis of aneurysmal walls and extracranial arteries with real-time polymerase chain reaction and immunohistochemistry. World Neurosurg 2019; 130:e117–e126.
Burghaus B, Langer C, Thedieck S, Nowak-Göttl U. Elevated alpha 1-antitrypsin is a risk factor for arterial ischemic stroke in childhood. Acta Haematol 2006; 115:186–191.
Moldthan HL, Hirko AC, Thinschmidt JS, et al. Alpha 1-antitrypsin therapy mitigated ischemic stroke damage in rats. J Stroke Cerebrovasc Dis 2014; 23:e355–e363.
Meschia JF. Alpha-1 antitrypsin dysfunction and large artery stroke. Proc Natl Acad Sci U S A 2017; 114:3555–3557.
Malik R, Dau T, Gonik M, et al. International Stroke Genetics Consortium. Common coding variant in SERPINA1 increases the risk for large artery stroke. Proc Natl Acad Sci U S A 2017; 114:3613–3618.
Mahta A, Yaghi S, Reznik ME, et al. Serum alpha-1 antitrypsin in acute ischemic stroke: a prospective pilot study. J Clin Neurosci 2020; 76:20–24.
Schachner T, Golderer G, Sarg B, et al. The amounts of alpha 1 antitrypsin protein are reduced in the vascular wall of the acutely dissected human ascending aorta. Eur J Cardiothorac Surg 2010; 37:684–690.
Vizzardi E, Corda L, Pezzali N, et al. Elastic properties of the ascending aorta in patients with α1-antitrypsin deficiency (Z homozygotes). Heart 2012; 98:1354–1358.
Vizzardi E, Corda L, Sciatti E, et al. Echocardiographic evaluation in subjects with α1-antitrypsin deficiency. Eur J Clin Invest 2015; 45:949–954.
Kilickesmez KO, Abaci O, Kocas C, et al. Dilatation of the ascending aorta and serum alpha 1-antitrypsin level in patients with bicuspid aortic valve. Heart Vessels 2012; 27:391–397.
Muhammad IF, Borné Y, Östling G, et al. Acute phase proteins as prospective risk markers for arterial stiffness: the Malmö Diet and Cancer cohort. PLoS One 2017; 12:e0181718.
Fisk M, Cheriyan J, Mohan D, et al. Vascular inflammation and aortic stiffness: potential mechanisms of increased vascular risk in chronic obstructive pulmonary disease. Respir Res 2018; 19:100.
Dako F, Zhao H, Mulvenna A, Gupta YS, Simpson S, Kueppers F. Relationship between α1-antitrypsin deficiency and ascending aortic distention. Mayo Clin Proc Innov Qual Outcomes 2021; 5:590–595.
Guo J, Lodge K, Newnham M, et al. Increased antielastase activity in idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Am J Respir Cell Mol Biol 2018; 59:652–655.
Aldonyte R, Jansson L, Ljungberg O, Larsson S, Janciauskiene S. Polymerized alpha-antitrypsin is present on lung vascular endothelium. New insights into the biological significance of alpha-antitrypsin polymerization. Histopathology 2004; 45:587–592.
Engström G, Stavenow L, Hedblad B, et al. Inflammation-sensitive plasma proteins and incidence of myocardial infarction in men with low cardiovascular risk. Arterioscler Thromb Vasc Biol 2003; 23:2247–2251.
Kanai T, Shiraishi H, Uehara R, Ito T, Momoi MY. Increased (1-antitrypsin levels in acute-phase Kawasaki disease as shown by SELDI-TOF MS analysis. Pediatr Cardiol 2012; 33:1343–1347.
Feng Y, Hu L, Xu Q, et al. Cytoprotective role of alpha-1 antitrypsin in vascular endothelial cell under hypoxia/reoxygenation condition. J Cardiovasc Pharmacol 2015; 66:96–107.
Abbate A, Van Tassell BW, Christopher S, et al. Effects of prolastin C (plasma-derived alpha-1 antitrypsin) on the acute inflammatory response in patients with ST-segment elevation myocardial infarction (from the VCU-alpha 1-RT pilot study). Am J Cardiol 2015; 115:8–12.
Toldo S, Mauro AG, Marchetti C, et al. Recombinant human alpha-1 antitrypsin-Fc fusion protein reduces mouse myocardial inflammatory injury after ischemia-reperfusion independent of elastase inhibition. J Cardiovasc Pharmacol 2016; 68:27–32.
Abouzaki NA, Christopher S, Trankle C, et al. Inhibiting the inflammatory injury after myocardial ischemia reperfusion with plasma-derived alpha-1 antitrypsin: a post hoc analysis of the VCU-α1RT Study. J Cardiovasc Pharmacol 2018; 71:375–379.
Turhan Caglar FN, Ksanski V, Polat V, et al. The association between α1-antitrypsin and coronary artery ectasia. Angiology 2016; 67:927–931.
Stakisaitis D, Basys V, Benetis R. Does alpha-1-proteinase inhibitor play a protective role in coronary atherosclerosis? Med Sci Monit 2001; 7:701–711.
Dahl M, Tybjaerg-Hansen A, Sillesen H, Jensen G, Steffensen R, Nordestgaard BG. Blood pressure, risk of ischemic cerebrovascular and ischemic heart disease, and longevity in alpha (1)-antitrypsin deficiency: the Copenhagen City Heart Study. Circulation 2003; 107:747–752.
Talmud PJ, Martin S, Steiner G, et al. Diabetes Atherosclerosis Intervention Study Investigators. Progression of atherosclerosis is associated with variation in the alpha 1-antitrypsin gene. Arterioscler Thromb Vasc Biol 2003; 23:644–649.
Towler DA. Arteriosclerotic calcification: a Serpi(n)ginous path to cardiovascular health? Circ Res 2015; 117:744–746.
Fähndrich S, Biertz F, Karch A, et al. COSYCONET investigators. Cardiovascular risk in patients with alpha-1-antitrypsin deficiency. Respir Res 2017; 18:171.
Curjuric I, Imboden M, Bettschart R, et al. Alpha-1 antitrypsin deficiency: from the lung to the heart? Atherosclerosis 2018; 270:166–172.
Nakanishi T, Forgetta V, Handa T, et al. The undiagnosed disease burden associated with alpha-1 antitrypsin deficiency genotypes. Eur Respir J 2020; 56:2001441.
Tilson MD, Roberts MP. Molecular diversity in the abdominal aortic aneurysm phenotype. Arch Surg 1988; 123:1202–1206.
Cohen JR, Sarfati I, Ratner L, Tilson D. Alpha 1-antitrypsin phenotypes in patients with abdominal aortic aneurysms. J Surg Res 1990; 49:319–321.
Schardey HM, Hernandez-Richter T, Klueppelberg U, Tutsch-Bauer E, Lauterjung L. Alleles of the alpha-1-antitrypsin phenotype in patients with aortic aneurysms. J Cardiovasc Surg (Torino) 1998; 39:535–539.
Elzouki AN, Eriksson S. Abdominal aortic aneurysms and alpha 1-antitrypsin deficiency. J Intern Med 1994; 236:587–591.
St Jean P, Hart B, Webster M, et al. Alpha-1-antitrypsin deficiency in aneurysmal disease. Hum Hered 1996; 46:92–97.
Hernandez-Richter T, Schardey HM, Klueppelberg U, Tutsch-Bauer E, Lauterjung L, Schildberg FW. Is heterozygote alpha 1-antitrypsin deficiency a risk factor in the etiology of aortic aneurysm? Chirurg 1997; 68:513–516.
Elzouki AN, Rydén Ahlgren A, Länne T, Sonesson B, Eriksson S. Is there a relationship between abdominal aortic aneurysms and alpha 1-antitrypsin deficiency (PiZ)? Eur J Vasc Endovasc Surg 1999; 17:149–154.
Ahlgren AR, Piitulainen E, Sonesson B, Länne T. Changes in aortic wall stiffness in men with alpha 1-antitrypsin deficiency. Eur J Vasc Endovasc Surg 1997; 14:252–257.
Knapik-Kordecka M, Doskocz R, Adamiec R. Stezenie alpha 1-antytrypsyny a czynniki ryzyka miazdzycy u chorych z tetniakiem aorty brzusznej [Alpha-1 antitrypsin concentration and atherosclerosis risk factors in patients with abdominal aortic aneurysm]. Pol Merkur Lekarski 2003; 14:425–427.
Vega de Céniga M, Esteban M, Quintana JM, et al. Search for serum biomarkers associated with abdominal aortic aneurysm growth: a pilot study. Eur J Vasc Endovasc Surg 2009; 37:297–299.
Pulinx B, Hellenthal FA, Hamulyák K, van Dieijen-Visser MP, Schurink GW, Wodzig WK. Differential protein expression in serum of abdominal aortic aneurysm patients: a proteomic approach. Eur J Vasc Endovasc Surg 2011; 42:563–570.
Pini L, Peroni M, Zanotti C, et al. Investigating the link between alpha-1 antitrypsin deficiency and abdominal aortic aneurysms. Ann Vasc Surg 2021; 77:195–201.
Gaglio PJ, Regenstein F, Slakey D, et al. Alpha-1 antitrypsin deficiency and splenic artery aneurysm rupture: an association? Am J Gastroenterol 2000; 95:1531–1534.
Bofinger A, Hawley C, Fisher P, Daunt N, Stowasser M, Gordon R. Alpha-1-antitrypsin phenotypes in patients with renal arterial fibromuscular dysplasia. J Hum Hypertens 2000; 14:91–94.
Perdu J, Gimenez-Roqueplo AP, Boutouyrie P, et al. Alpha 1-antitrypsin gene polymorphisms are not associated with renal arterial fibromuscular dysplasia. J Hypertens 2006; 24:705–710.
Mazodier P, Elzouki AN, Segelmark M, Eriksson S. Systemic necrotizing vasculitides in severe alpha 1-antitrypsin deficiency. QJM 1996; 89:599–611.
Savige JA, Chang L, Cook L, Burdon J, Daskalakis M, Doery J. Alpha 1-antitrypsin deficiency and antiproteinase 3 antibodies in antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis. Clin Exp Immunol 1995; 100:194–197.
Callea F, Gregorini G, Sinico A, et al. alpha 1-antitrypsin (AAT) deficiency and ANCA-positive systemic vasculitis: genetic and clinical implications. Eur J Clin Invest 1997; 27:696–702.
Wakefield D, Easter J, Breit SN, Clark P, Penny R. Alpha 1 antitrypsin serum levels and phenotypes in patients with retinal vasculitis. Br J Ophthalmol 1985; 69:497–499.
Audrain MA, Sesboüé R, Baranger TA, et al. Analysis of antineutrophil cytoplasmic antibodies (ANCA): frequency and specificity in a sample of 191 homozygous (PiZZ) alpha 1-antitrypsin-deficient subjects. Nephrol Dial Transplant 2001; 16:39–44.