Abdominal aortic aneurysms

Sakalihasan, Natzi; Michel, Jean‐Baptiste; Katsargyris, Αthanasios; Kuivaniemi, Helena; Defraigne, Jean-Olivier; Nchimi, Alain; Powell, Janet T.; Yoshimura, Kenichi; Hultgren, Rebecka

doi:10.1038/s41572-018-0030-7

Cited by 426 publications

(439 citation statements)

References 249 publications

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“…Aortic aneurysm/dissection are characterized by extensive molecular changes in the vascular wall and the synthetic phenotype of VSMCs. Multiple mechanisms have been proposed to promote the pathogenesis of aortic aneurysm/dissection, including vascular inflammation, oxidative stress, extracellular matrix (ECM) degradation, and VSMC dedifferentiation (23). In the present study, we found that VSMC-EP4 −/− mice exhibit significantly higher aortic MCP-1 expression and more macrophage infiltration in comparison with WT animals.…”

Section: Discussionsupporting

confidence: 54%

VSMC-specific EP4 deletion exacerbates angiotensin II-induced aortic dissection by increasing vascular inflammation and blood pressure

Fang

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Prostaglandin E2 (PGE2) plays an important role in vascular homeostasis. Its receptor, E-prostanoid receptor 4 (EP4) is essential for physiological remodeling of the ductus arteriosus (DA). However, the role of EP4 in pathological vascular remodeling remains largely unknown. We found that chronic angiotensin II (AngII) infusion of mice with vascular smooth muscle cell (VSMC)-specific EP4 gene knockout (VSMC-EP4−/−) frequently developed aortic dissection (AD) with severe elastic fiber degradation and VSMC dedifferentiation. AngII-infused VSMC-EP4−/−mice also displayed more profound vascular inflammation with increased monocyte chemoattractant protein-1 (MCP-1) expression, macrophage infiltration, matrix metalloproteinase-2 and -9 (MMP2/9) levels, NADPH oxidase 1 (NOX1) activity, and reactive oxygen species production. In addition, VSMC-EP4−/−mice exhibited higher blood pressure under basal and AngII-infused conditions. Ex vivo and in vitro studies further revealed that VSMC-specific EP4 gene deficiency significantly increased AngII-elicited vasoconstriction of the mesenteric artery, likely by stimulating intracellular calcium release in VSMCs. Furthermore, EP4 gene ablation and EP4 blockade in cultured VSMCs were associated with a significant increase in MCP-1 and NOX1 expression and a marked reduction in α-SM actin (α-SMA), SM22α, and SM differentiation marker genes myosin heavy chain (SMMHC) levels and serum response factor (SRF) transcriptional activity. To summarize, the present study demonstrates that VSMC EP4 is critical for vascular homeostasis, and its dysfunction exacerbates AngII-induced pathological vascular remodeling. EP4 may therefore represent a potential therapeutic target for the treatment of AD.

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Section: Discussionsupporting

confidence: 54%

VSMC-specific EP4 deletion exacerbates angiotensin II-induced aortic dissection by increasing vascular inflammation and blood pressure

Fang

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…TWEAK and Fn14 are expressed in human AAA colocalizing with macrophages and SMCs [83] and the role of TWEAK/Fn14 axis has been demonstrated in the experimental model of elastase-induced AAA [84]. A main pathological feature of AAA includes: extracellular matrix remodeling, loss of SMCs, accumulation/activation of inflammatory cells, and formation of intraluminal thrombus [85]. Infiltration of inflammatory cells (macrophages, T cells, neutrophils, and dendritic cells) is a crucial process in AAA development, driving the progressive and pathological remodeling of the aorta [85].…”

Section: Tweak and Abdominal Aortic Aneurysmmentioning

confidence: 99%

“…A main pathological feature of AAA includes: extracellular matrix remodeling, loss of SMCs, accumulation/activation of inflammatory cells, and formation of intraluminal thrombus [85]. Infiltration of inflammatory cells (macrophages, T cells, neutrophils, and dendritic cells) is a crucial process in AAA development, driving the progressive and pathological remodeling of the aorta [85]. There are three major chemokine/chemokine-receptor pathways controlling recruitment of circulating monocytes: CCL2/CCR2, CCL5/CCR5, and CX3CL1/CX3CR1, which are the most studied in the context of AAA [86,87].…”

Section: Tweak and Abdominal Aortic Aneurysmmentioning

confidence: 99%

Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK)/Fibroblast Growth Factor-Inducible 14 (Fn14) Axis in Cardiovascular Diseases: Progress and Challenges

Gutiérrez-Muñoz

Blázquez-Serra

Martı́n-Ventura

et al. 2020

Cells

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Cardiovascular diseases (CVD) are the leading cause of mortality in Western countries. CVD include several pathologies, such as coronary artery disease, stroke, peripheral artery disease, and aortic aneurysm, among others. All of them are characterized by a pathological vascular remodeling in which inflammation plays a key role. Interaction between different members of the tumor necrosis factor superfamily and their cognate receptors induce several biological actions that may participate in CVD. The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its functional receptor, fibroblast growth factor-inducible 14 (Fn14), are abundantly expressed during pathological cardiovascular remodeling. The TWEAK/Fn14 axis controls a variety of cellular functions, such as proliferation, differentiation, and apoptosis, and has several biological functions, such as inflammation and fibrosis that are linked to CVD. It has been demonstrated that persistent TWEAK/Fn14 activation is involved in both vessel and heart remodeling associated with acute and chronic CVD. In this review, we summarized the role of the TWEAK/Fn14 axis during pathological cardiovascular remodeling, highlighting the cellular components and the signaling pathways that are involved in these processes.

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“…Enlargement > 1.5 times the expected diameter is considered an aneurysm [1]. Close to 90% of aortic aneurysms (AAs) are found in the abdominal aorta, where the typical clinical diameter threshold for an aneurysm is 30 mm, although individual anatomy may vary, and women can have smaller baseline diameters [2]. The aneurysmal size criteria in thoracic aorta differ somewhat from those in abdominal aorta, and are dependent on the site of the lesion [3,4].…”

Section: Aortic Aneurysm Diseasementioning

confidence: 99%

Long noncoding RNAs in key cellular processes involved in aortic aneurysms

Trenner

Boon

et al. 2020

Atherosclerosis

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This current review covers studies that have identified long non-coding RNAs in aortic aneurysm development and progression. • We separately discuss transcripts and mechanisms of importance to thoracic as well as abdominal aortic aneurysms. • Functional data on lncRNAs being identified are highlighted. • Some have been studied in human as well as experimental models of the disease pathology.

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Abdominal aortic aneurysms

Cited by 426 publications

References 249 publications

VSMC-specific EP4 deletion exacerbates angiotensin II-induced aortic dissection by increasing vascular inflammation and blood pressure

VSMC-specific EP4 deletion exacerbates angiotensin II-induced aortic dissection by increasing vascular inflammation and blood pressure

Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK)/Fibroblast Growth Factor-Inducible 14 (Fn14) Axis in Cardiovascular Diseases: Progress and Challenges

Long noncoding RNAs in key cellular processes involved in aortic aneurysms

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