MicroRNAs and Current Concepts on the Pathogenesis of Abdominal Aortic Aneurysm

Joviliano, Edwaldo Edner; Ribeiro, Mauricio Serra; Tenorio, Emanuel Junior Ramos

doi:10.21470/1678-9741-2016-0050

Edwaldo Edner Joviliano Correspondence Address: Edwaldo Edner Joviliano, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, Departamento de Cirurgia e Anatomia, Av. Bandeirantes, 3900 - Ribeirão Preto, SP, Brazil - Zip code: 14048-900. E-mail: eejov@fmrp.usp.br

Department of Surgery and Anatomy, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.

Mauricio Serra Ribeiro

Department of Surgery and Anatomy, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.

Emanuel Junior Ramos Tenorio

Department of Surgery and Anatomy, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.

Correspondence Address: Edwaldo Edner Joviliano, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, Departamento de Cirurgia e Anatomia, Av. Bandeirantes, 3900 - Ribeirão Preto, SP, Brazil - Zip code: 14048-900. E-mail: eejov@fmrp.usp.br

No conflict of interest.

Figures (3)
Tables (4)

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Fig.1
Schematic representation of the impact of the blood-chronic intraluminal thrombus interface on medial degradation and the adventitial inflammatory, angiogenic and fibrotic responses in human AAA. Abbreviations: ATLO, adventitial tertiary lymphoid organ; and RBCs, red blood cells.

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Fig. 2
A general model of miRNA biogenesis and function.

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Fig. 3
Pathophysiology of abdominal aortic aneurysms. Schematic diagram illustrating events thought to contribute to the development and progression of abdominal aortic aneurysms. Injury to the aortic wall, either as a consequence of or in association with known risk factors (I), leads to recruitment of leukocytes into the aortic media (II), macrophage (MPh) activation, and production of proinflammatory molecules (III). Macrophages also produce proenzyme forms of matrix metalloproteinases (MMPs) (pro-MMPs) (IV), which are activated in the extracellular space (V). Tissue inhibitors of matrix metalloproteinases (TIMPs) may neutralize MMP activity (VI), but this neutralization appears insufficient to prevent degradation of structural matrix proteins (elastin and interstitial collagens) (VII). Over a period of years, elastin degradation, cyclic strain, and elevated wall tension bring about progressive aortic dilatation (VIII). Collagen degradation further weakens the aortic wall (IX); although medial smooth muscle cells (SMCs) and fibroblasts might promote structural repair, apoptosis, and cellular senescence cause SMC depletion (X), and interstitial collagen appears disorganized (XI). Aneurysm tissues exhibit infiltration by T cells, B lymphocytes, plasma cells, and dendritic cells and local deposition of immunoglobulins, reflecting a cellular and humoral immune response (XII). Understanding the adaptive cellular immune response in abdominal aortic aneurysms may reveal how different T-cell subsets (i.e., helper T cell type 1 [Th1] versus Th2) interact with macro- phages to promote or suppress aneurysmal degeneration, on the basis of the local balance of proinflammatory (XIII) and anti-inflammatory (XIV) molecules. Some cytokines produced within aneurysm tissue, such as interleukin-6 (IL-6) and interferon-γ (IFN-γ), may have dual and opposing functions depending on the specific context (XV). The promotion of miR-29 induces the extracellular matrix degradation and induces the formation of aneurysms (XVI). EDPs, Elastin degradation peptides; PGs, prostaglandins; ROS, reactive oxygen species; TGF-β, transforming growth factor-β; TNF-α, tumor necrosis factor-α; miR-29, microRNA-29^[⁷⁰70 Curci JA, Thompson RW. Adaptive cellular immunity in aortic aneurysms: cause, consequence, or context? J Clin Invest. 2004;114(2):168-71.^].

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Abbreviations, acronyms & symbols AAA = Abdominal aortic aneurysms COPD = Chronic obstructive pulmonary disease EVAR = Endovascular aneurysm repair JNK = c-Jun N-terminal kinase MMPs = Matrix metalloproteinases SMCs = Smooth muscle cells TAAs = Thoracic aortic aneurysms TIMPs = Tissues by metalloproteinase inhibitors

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Table 1
Independent risk factors for AAA ≥ 4 cm.

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Table 2
Estimated annual rupture risk.

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Authors' roles & responsibilities EEJ Conception and design of the work; final approval of the version to be published MSR Revising it critically for important intellectual content; final approval of the version to be published EJRT Acquisition, analysis, and interpretation of data for the work; final approval of the version to be published

Abbreviations, acronyms & symbols
AAA	= Abdominal aortic aneurysms
COPD	= Chronic obstructive pulmonary disease
EVAR	= Endovascular aneurysm repair
JNK	= c-Jun N-terminal kinase
MMPs	= Matrix metalloproteinases
SMCs	= Smooth muscle cells
TAAs	= Thoracic aortic aneurysms
TIMPs	= Tissues by metalloproteinase inhibitors

Risk Factor	Odds Ratio	95% CI
Increased Risk
Smoking history	5.1	4.1-6.2
Family history of AAA	1.9	1.6-2.3
Older age (per 7-year interval)	1.7	1.6-1.8
Coronary artery disease	1.5	1.4-1.7
High cholesterol	1.4	1.3-1.6
COPD	1.2	1.1-1.4
Height (per 7-cm interval)	1.2	1.1-1.3
Decreased Risk
Abdominal imaging within 5 years	0.8	0.7-0.9
Deep venous thrombosis	0.7	0.5-0.8
Diabetes mellitus	0.5	0.5-0.6
Black race	0.5	0.4-0.7
Female gender	0.2	0.1-0.5

AAA diameter (cm)	Rupture risk (%/y)
< 4	0
4 – 5	0.5 – 5
5 – 6	3 – 15
6 – 7	10 – 20
7 – 8	20 – 40
> 8	30 – 50

Authors' roles & responsibilities
EEJ	Conception and design of the work; final approval of the version to be published
MSR	Revising it critically for important intellectual content; final approval of the version to be published
EJRT	Acquisition, analysis, and interpretation of data for the work; final approval of the version to be published

[1] Correspondence Address: Edwaldo Edner Joviliano, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, Departamento de Cirurgia e Anatomia, Av. Bandeirantes, 3900 - Ribeirão Preto, SP, Brazil - Zip code: 14048-900. E-mail: eejov@fmrp.usp.br

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MicroRNAs and Current Concepts on the Pathogenesis of Abdominal Aortic Aneurysm

Abstract