Molecular Pathogenesis and the Possible Role of Mitochondrial Heteroplasmy in Thoracic Aortic Aneurysm

Overview

Journal Life (Basel)

Specialty Biology

Date 2021 Dec 24

PMID 34947926

Citations 2

Authors

A V Suslov

M A Afanasyev

P A Degtyarev

P V Chumachenko

M Bagheri Ekta

V N Sukhorukov

V A Khotina

S-F Yet

I A Sobenin

A Yu Postnov

Affiliations

Soon will be listed here.

Abstract

Thoracic aortic aneurysm (TAA) is a life-threatening condition associated with high mortality, in which the aortic wall is deformed due to congenital or age-associated pathological changes. The mechanisms of TAA development remain to be studied in detail, and are the subject of active research. In this review, we describe the morphological changes of the aortic wall in TAA. We outline the genetic disorders associated with aortic enlargement and discuss the potential role of mitochondrial pathology, in particular mitochondrial DNA heteroplasmy, in the disease pathogenesis.

Citing Articles

Calciprotein particles induce arterial stiffening ex vivo and impair vascular cell function.

Neutel C, Wesley C, van Loo C, Civati C, Mertens F, Zurek M Commun Biol. 2024; 7(1):1241.

PMID: 39358413 PMC: 11447031. DOI: 10.1038/s42003-024-06895-y.

A yeast based assay establishes the pathogenicity of novel missense ACTA2 variants associated with aortic aneurysms.

Calderan C, Sorrentino U, Persano L, Trevisson E, Sartori G, Salviati L Eur J Hum Genet. 2024; 32(7):804-812.

PMID: 38486025 PMC: 11219741. DOI: 10.1038/s41431-024-01591-1.

References

Rossignol R, Faustin B, Rocher C, Malgat M, Mazat J, Letellier T . Mitochondrial threshold effects. Biochem J. 2002; 370(Pt 3):751-62. PMC: 1223225. DOI: 10.1042/BJ20021594. View

Kulek A, Anzell A, Wider J, Sanderson T, Przyklenk K . Mitochondrial Quality Control: Role in Cardiac Models of Lethal Ischemia-Reperfusion Injury. Cells. 2020; 9(1). PMC: 7016592. DOI: 10.3390/cells9010214. View

Liao B, Zhou M, Zhou F, Luo X, Zhong S, Zhou Y . Exosome-Derived MiRNAs as Biomarkers of the Development and Progression of Intracranial Aneurysms. J Atheroscler Thromb. 2019; 27(6):545-610. PMC: 7355105. DOI: 10.5551/jat.51102. View

Homme J, Aubry M, Edwards W, Bagniewski S, Pankratz V, Kral C . Surgical pathology of the ascending aorta: a clinicopathologic study of 513 cases. Am J Surg Pathol. 2006; 30(9):1159-68. DOI: 10.1097/01.pas.0000213270.38091.69. View

Kaarniranta K, Pawlowska E, Szczepanska J, Jablkowska A, Blasiak J . Role of Mitochondrial DNA Damage in ROS-Mediated Pathogenesis of Age-Related Macular Degeneration (AMD). Int J Mol Sci. 2019; 20(10). PMC: 6566654. DOI: 10.3390/ijms20102374. View

Picca A, Lezza A, Leeuwenburgh C, Pesce V, Calvani R, Landi F . Fueling Inflamm-Aging through Mitochondrial Dysfunction: Mechanisms and Molecular Targets. Int J Mol Sci. 2017; 18(5). PMC: 5454846. DOI: 10.3390/ijms18050933. View

Arias M, Sauer-Lehnen S, Treptau J, Janoschek N, Theuerkauf I, Buettner R . Adenoviral expression of a transforming growth factor-beta1 antisense mRNA is effective in preventing liver fibrosis in bile-duct ligated rats. BMC Gastroenterol. 2003; 3:29. PMC: 270053. DOI: 10.1186/1471-230X-3-29. View

Zhang S, Wei C, Wang Q, Wang L, Lu L, Qi F . M2-polarized macrophages mediate wound healing by regulating connective tissue growth factor via AKT, ERK1/2, and STAT3 signaling pathways. Mol Biol Rep. 2021; 48(9):6443-6456. DOI: 10.1007/s11033-021-06646-w. View

Miller D, Isotalo P, Weyand C, Edwards W, Aubry M, Tazelaar H . Surgical pathology of noninfectious ascending aortitis: a study of 45 cases with emphasis on an isolated variant. Am J Surg Pathol. 2006; 30(9):1150-8. DOI: 10.1097/01.pas.0000213293.04026.ec. View

10.

Pasta S, Agnese V, Gallo A, Cosentino F, Di Giuseppe M, Gentile G . Shear Stress and Aortic Strain Associations With Biomarkers of Ascending Thoracic Aortic Aneurysm. Ann Thorac Surg. 2020; 110(5):1595-1604. DOI: 10.1016/j.athoracsur.2020.03.017. View

11.

Stewart J, Chinnery P . The dynamics of mitochondrial DNA heteroplasmy: implications for human health and disease. Nat Rev Genet. 2015; 16(9):530-42. DOI: 10.1038/nrg3966. View

12.

Garbern J, Williams J, Kristl A, Malick A, Rachmin I, Gaeta B . Dysregulation of IL-33/ST2 signaling and myocardial periarteriolar fibrosis. J Mol Cell Cardiol. 2019; 128:179-186. PMC: 6402609. DOI: 10.1016/j.yjmcc.2019.01.018. View

13.

Wu L, Luo Z, Zheng J, Yao P, Yuan Z, Lv X . IL-33 Can Promote the Process of Pulmonary Fibrosis by Inducing the Imbalance Between MMP-9 and TIMP-1. Inflammation. 2018; 41(3):878-885. DOI: 10.1007/s10753-018-0742-6. View

14.

Richter K, Konzack A, Pihlajaniemi T, Heljasvaara R, Kietzmann T . Redox-fibrosis: Impact of TGFβ1 on ROS generators, mediators and functional consequences. Redox Biol. 2015; 6:344-352. PMC: 4565043. DOI: 10.1016/j.redox.2015.08.015. View

15.

Lederle F, Johnson G, Wilson S, Chute E, Littooy F, Bandyk D . Prevalence and associations of abdominal aortic aneurysm detected through screening. Aneurysm Detection and Management (ADAM) Veterans Affairs Cooperative Study Group. Ann Intern Med. 1997; 126(6):441-9. DOI: 10.7326/0003-4819-126-6-199703150-00004. View

16.

Sverdlov A, Elezaby A, Qin F, Behring J, Luptak I, Calamaras T . Mitochondrial Reactive Oxygen Species Mediate Cardiac Structural, Functional, and Mitochondrial Consequences of Diet-Induced Metabolic Heart Disease. J Am Heart Assoc. 2016; 5(1). PMC: 4859372. DOI: 10.1161/JAHA.115.002555. View

17.

Milewicz D, Trybus K, Guo D, Sweeney H, Regalado E, Kamm K . Altered Smooth Muscle Cell Force Generation as a Driver of Thoracic Aortic Aneurysms and Dissections. Arterioscler Thromb Vasc Biol. 2016; 37(1):26-34. PMC: 5222685. DOI: 10.1161/ATVBAHA.116.303229. View

18.

Bunton T, Biery N, Myers L, Gayraud B, Ramirez F, Dietz H . Phenotypic alteration of vascular smooth muscle cells precedes elastolysis in a mouse model of Marfan syndrome. Circ Res. 2001; 88(1):37-43. DOI: 10.1161/01.res.88.1.37. View

19.

Su S, Xie Y, Fu Z, Wang Y, Wang J, Xiang M . Emerging role of exosome-mediated intercellular communication in vascular remodeling. Oncotarget. 2017; 8(15):25700-25712. PMC: 5421963. DOI: 10.18632/oncotarget.14878. View

20.

Kong P, Christia P, Frangogiannis N . The pathogenesis of cardiac fibrosis. Cell Mol Life Sci. 2013; 71(4):549-74. PMC: 3769482. DOI: 10.1007/s00018-013-1349-6. View